Echinocandin-like and boron-containing echinocandin compounds and their use as agrochemical fungicides

Abstract

Compositions and methods for controlling plant pathogens and / or for increasing plant yield and health are provided. Compositions comprise at least one antifungal compound or derivative or variant thereof from the lipophilic cyclic hexapeptide echinocandin family active against and can control at least one or more pathogens that cause plant disease and an agriculturally acceptable adjuvant. Compositions may also comprise boron containing echinocandins that are useful for the treatment or control of plant pathogens. Compositions may comprise additional antifungal agents. The compositions may be used as inoculants for plants to control plant disease. Therefore, methods for controlling plant disease and increasing yield by applying an effective amount of the composition to a plant, plant part, or area of cultivation of plants are provided.

Description

[0001] Echinocandin-like and Boron-containing Echinocandin Compounds and Their Use as Agrochemical Fungicides

[0002] CROSS REFERENCE TO PRIORITY APPLICATION

[0003] The application claims priority to U.S. Provisional Application No. 63 / 645,732, filed May 10, 2024, which is incorporated herein by reference in its entirety.

[0004] FIELD

[0005] Described herein are antifungal lipophilic cyclic hexapeptidal candins, fungins, and derivatives thereof and their use for controlling plant disease and improving agricultural yield.

[0006] BACKGROUND

[0007] Plant infections caused by pathogenic fungi are a continuing and serious problem. Fungal pathogens are responsible for major damage to crop plants and for significant crop losses. The damage is characterized by wilting, scabs, moldy coatings, rust, blotches and rotted tissue. These fungal pathogens are responsible for about eighty-five percent of all plant diseases. Diseases like powdery mildew, Cercospora leaf spot, root rot, and anthracnose are caused by different fungal species. However, most plant diseases are caused by five main groups of fungus or fungus like organism: Ascomycota; Basidiomycota; Deuteromycota (fungi imperfecti); Oomycota; and Zygomycota.

[0008] The control of plant diseases caused by fungal plant pathogens is extremely important in achieving high crop efficiency. Plant disease damage to ornamental, vegetable, field, cereal, and fruit crops can cause significant reduction in productivity and thereby result in increased costs to the consumer. Many products are commercially available for these purposes, but the need continues for new compounds which are more effective, less costly, less toxic, environmentally safer, or have different sites of action.

[0009] Boron is a unique element due to its capacity to create powerfully effective compounds. Until recently, boron had been largely ignored by medicinal chemists due to limited known reactions to install boron and potential toxicity concerns in drug design. Many challenges remain in extending the applicability of boron. One significant challenge is the technical limitations of virtual screening, which has become an important tool in drug discovery. Another problem is that boronic acids are less stable than aldehydes and acrylates, and thus may be degraded before binding to the target. While the use of boron as simple naturally occurring borates is well known, the construction and characterization of more complex rationally designed boron-containing synthetic compounds that have low toxicity and are effective has been relatively under investigated. Methods are needed to use the advantages of boron to increase the efficacy and stability of useful compounds to control plant disease.

[0010] SUMMARY

[0011] Compositions and methods for controlling pathogens, particularly plant pathogens, and / or for increasing plant yield and health are provided. The compositions described herein include at least one antifungal compound encompassed by Formulas I-XIII and selected from cyclolipohexapeptides, candins, fungins and derivatives thereof (referred to herein as “echinocandins” or “echinocandin-like compounds”), active against and capable of controlling at least one or more pathogens that cause plant disease, and a suitable agricultural adjuvant. Compositions including echinocandin-like compounds and agriculturally relevant adjuvants, as described herein, may include additional antifungal agents. The compositions may be used to control plant diseases.

[0012] Also described herein are compositions and methods for modifying and improving echinocandin and echinocandin-like chemical compounds by the incorporation of boron into the structure. In particular, the echinocandin compounds described herein are modified to incorporate at least one boron into the structure and are those encompassed by Formulas VII- XIII. The boron containing compounds may exhibit unique binding properties to biological targets. Boron substitutions of the compounds and compositions described herein are made to modulate biological activity, pharmacokinetic properties, off target toxicity and resistance. Additionally, modified compounds may be formulated as pro-drugs that release the bioactive molecule in a desired fashion.

[0013] The modified compounds described herein are provided in compositions for controlling pathogens, particularly plant pathogens, and / or for increasing plant yield and health. The compositions described herein include at least one antifungal compound encompassed by Formulas I-XIII and selected from cyclolipohexapeptides, candins, fungins and derivatives thereof (referred to herein as “echinocandins” or “echinocandin-like compounds”), active against and capable of controlling at least one or more pathogens that cause plant disease, and a suitable agricultural adjuvant or carrier. Compositions including echinocandin-like compounds and agriculturally relevant adjuvants, as described herein, may include additional agents, including additional antifungal agents and growth enhancers. In some embodiments, the compounds described herein are used in combination with other antifungal agents with different mechanisms of action and are likely to provide enhanced efficacy or synergy. The compositions may be used to control plant diseases. Methods for controlling plant disease and increasing yield by applying an effective amount of the compositions described herein to a plant, plant part, seed, or area of cultivation of plants are provided.

[0014] In some examples, the compounds described herein may be useful in animal, including human, applications, as many of the echinocandins are used for pharmaceutical applications. Thus, pharmaceutical compositions comprising the echinocandin-like compounds and a pharmaceutically acceptable carrier as well as methods of use to treat, prevent, or control animal diseases or conditions are provided.

[0015] DETAILED DESCRIPTION

[0016] Compositions comprising echinocandins, echinocandin derivatives, boron containing echinocandins, or boron containing echinocandin derivatives (referred to herein as echinocandin or echinocandin-like compounds) useful as antifungals are provided. In particular, the compositions and methods provided herein are useful for preventing, treating, and controlling plant pathogens and / or for increasing plant yield and plant health. The compositions include antifungal compounds or derivatives disclosed herein from or derived from the Echinocandin family. Such echinocandin-like compounds can be used for the treatment of fungal infections.

[0017] The natural echinocandins, such as echinocandin B, are a family of closely related cyclolipohexapeptides that were isolated from fermentation broths of various microbial cultures. Structurally, the echinocandins are composed of a complex cyclohexapeptide whose N-terminus is acylated by a long carboxylic acid chain. The echinocandin-like compounds described herein are cyclic hexapeptides but comprise 3 -methyl glutamine in place of glutamine and 3-hydroxyproline in place of 3-hydroxy-4-hydroxy methyl proline, as included in naturally occurring cryptocandins. Additionally, the compounds may have a boron incorporated into their structure.

[0018] Echinocandins have a unique mechanism of action. They act by specific and noncompetitive inhibition of P-(l, 3)-D-glucan synthase, an enzyme that is necessary for the synthesis of an essential component of the fungal cell wall. The inhibition of glucan biosynthesis leads to a weakened cell wall, which results in cell content leakage and cell death. The echinocandin-like compounds described herein display antifungal potency, a unique mode of action, and a low toxicity. The echinocandin-like compounds described herein do not include cryptocandin or any echinocandin-like compound made by the microorganism Cryptosporiosis .

[0019] Antifungal Compounds

[0020] Described herein are echinocandins, boron containing echinocandins, and derivatives or variants thereof (echinocandin-like compounds or echinocandin-like antifungals) for use in treating plant fungal pathogens. The compounds described herein are antifungal agents active against various plant fungal organisms. They are useful in controlling plant infection and disease. Additionally, the compositions find use in controlling fungal pathogens in industrial applications. Compounds of the disclosure include those shown below represented by Formulas I-XIII.

[0021] Compounds according to Formula I are depicted in the structure below:

[0022] Formula I wherein:

[0023] U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0024] V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;

[0025] W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, CH2Q, N3, NO2, Cl, F, Br, and I;

[0026] X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM;

[0027] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and OC(O)R;

[0028] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q, wherein the compounds may include R, S, or mixtures of R and S isomers at Z;

[0029] T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;

[0030] Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R, or optionally taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0031] Compounds according to Formula II are depicted in the structure below:

[0032]

[0033] Formula II wherein:

[0034] U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0035] V is selected from the group consisting of H, methyl, and hydroxyl; T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl,

[0036] C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and C(O)OR; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and, each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0037] The compounds according to Formula III are depicted in the structure below: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0038] V is selected from the group consisting of H, methyl, and hydroxyl;

[0039] X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and, each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0040] Compounds according to Formula IV are depicted in the structure below:

[0041] Formula IV wherein:

[0042] U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0043] V is selected from the group consisting of H, methyl, and hydroxyl;

[0044] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and NR(0)R’; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and, each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0045] Compounds according to Formula V are depicted in the structure below:

[0046] Formula V wherein:

[0047] U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0048] V is selected from the group consisting of H, methyl, and hydroxyl;

[0049] W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, CH2Q, and CN; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;

[0050] Q is selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, and I; and, NR(0)R’; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0051] Compounds according to Formula VI are depicted in the structure below:

[0052] U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0053] V is selected from the group consisting of H, methyl, and hydroxyl;

[0054] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, NR(O)R’, F, Cl, Br, I, and CH2Q, wherein the compounds may include R, S, or mixtures of R and S isomers at Z;

[0055] Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or optionally taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0056] Methods of the disclosure include the modification of echinocandin compounds to improve biological properties and their use as antifungal agents. The incorporation of boron has diverse applications in the construction of therapeutically useful bioactive echinocandin molecules. Boronic acid related functional groups are unique in several ways. Boron- containing compounds bind to biological targets through reversible covalent bonds, multiple hydrogen bonds or metal ion coordination bonds, facilitating biological activity and potentially overcoming resistance. Additionally, the boronated compounds described herein may be designed as prodrugs to improve drug targeting or delivery. Further, in some embodiments, bioorthogonal reactions involving boronic acid may be used to generate larger molecules intracellularly to overcome permeability issues. The more metabolically labile boron species may also allow for faster metabolic degradation and therefore lower off-target toxic effects in comparison to the non-boronated analog. In creating the boron-containing compounds, logical placement or computer aided design and molecular modeling may be utilized.

[0057] Boron-containing compounds according to Formulas VII-XIII are depicted in the structures below:

[0058] Formula IX Formula X

[0059]

[0060] Formula XI Formula XII

[0061] In Formula VII, VIII, IX, X, XI, and / or XII:

[0062] U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0063] V is selected from the group consisting of H, methyl, and hydroxyl;

[0064] A is N or O; n is 0-3;

[0065] W is carbonyl or CH2;

[0066] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;

[0067] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q wherein the compounds may include R, S, or mixtures of R and S isomers at Z;

[0068] Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or optionally taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0069] Compounds according to Formula XIII are depicted in the structure below:

[0070] where:

[0071] U is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, C(O)alkyl, C(O)aryl, C(O)heteroalkyl, and C(O)heteroaryl or a group consisting of: wherein n is 3-9;

[0072] K is H or -OH;

[0073] V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;

[0074] L is -OH, -B(OH)2, -B(OR)2or selected from a group consisting of: wherein R* is independently alkyl and joined as ring or alkyl-substituted ring and n is 0-3;

[0075] A is either O or NH;

[0076] W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, CH2Q, N3, NO2, Cl, F, Br, I and a group as follows: wherein R* is independently alkyl and joined as ring or alkyl-substituted ring and n is 0-3;

[0077] X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM;

[0078] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and OC(O)R;

[0079] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q, wherein the compounds may include d, S, or mixtures of R and S isomers at Z;

[0080] T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;

[0081] Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or optionally taken together with K to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0082] Compositions include one or more compounds according to Formula I - XIII or an agriculturally acceptable acid, addition salt and / or hydrate thereof. The compositions of the disclosure can further include a suitable agricultural adjuvant, and optionally another fungicidal compound or pesticidal compound. Throughout the specification and claims, a given chemical formula or name shall encompass all optical and stereoisomers as well as racemic mixtures where such isomers and mixtures exist. The term “alkyl,” by itself or as part of another substituent, means, unless otherwise stated, a straight or branched chain, or cyclic hydrocarbon radical, or combination thereof, which may be fully saturated, mono- or polyunsaturated and can include di-, tri- and multivalent radicals, having the number of carbon atoms designated (i.e., C1-C10 means one to ten carbons).

[0083] Examples of saturated hydrocarbon radicals include, but are not limited to, groups such as methyl, ethyl, w-propyl, isopropyl, / / -butyl, / -butyl, isobutyl, sec-butyl, cyclohexyl, (cyclohexyl)methyl, cyclopropylmethyl, homologs and isomers of, for example, w-pentyl, n- hexyl, w-heptyl, w-octyl, and the like. An unsaturated alkyl group is one having one or more double bonds or triple bonds. Examples of unsaturated alkyl groups include, but are not limited to, vinyl, 2-propenyl, crotyl, 2-isopentenyl, 2-(butadienyl), 2,4-pentadienyl, 3-(l,4- pentadienyl), ethynyl, 1- and 3-propynyl, 3-butynyl, and the higher homologs and isomers. The term “alkyl,” unless otherwise noted, is also meant to optionally include those derivatives of alkyl defined in more detail below, such as “heteroalkyl.” Alkyl groups that are limited to hydrocarbon groups are termed “homoalkyl.” Exemplary alkyl groups include the monounsaturated C9.10, oleoyl chain or the diunsaturated C9.i0, 12-13 linoeyl chain.

[0084] The terms “alkoxy,” “alkylamino” and “alkylthio” (or thioalkoxy) are used in their conventional sense, and refer to those alkyl groups attached to the remainder of the molecule via an oxygen atom, an amino group, or a sulfur atom, respectively.

[0085] A heterocycloalkyl group may be unsubstituted or substituted, with the term “substituted heterocycloalkyl” referring to heterocycloalkyl groups substituted with one or more groups including, but not limited to halogen, hydroxy, alkyl, cycloalkyl, heteroalkyl, alkoxy, aryloxy, alkanoyl, aroyl, alkylester, arylester, cyano, sulfonyl, thio, amino, substituted amino, amido, lactam, urea, aryl, substituted aryl, heterocyclo, substituted heterocyclo, or any combination thereof.

[0086] The term “heteroalkyl” refers to alkyl groups in which at least one carbon atom is substituted by N, O, S, Si or P. This includes but is not limited to alkoxy groups, aminoalkyl groups, alkylamino groups, alkoxyamino groups, thioalkyl groups, alkoxyalkyl groups, alkoxythio groups, and thioalkylamino groups. The term “alkoxy” is used in its conventional sense, and refers to those alkyl groups attached to the remainder of the molecule via an oxygen atom. Representative examples of “alkoxy” include, but are not limited to, methoxy, ethoxy, propoxy, 2-propoxy, butoxy, Zc / 'Z-butoxy, hydroxylethyloxy and aminoethyloxy. The term “aminoalkyl” is used in its conventional sense, and refers to those alkyl groups attached to the remainder of the molecule via a nitrogen atom. The term “thioalkyl” is used in its conventional sense, and refers to those alkyl groups attached to the remainder of the molecule via a sulfur atom. Representative examples of heteroalkyl groups include but are not limited to methoxy, ethoxy, ethoxyamine, ethoxy-N,N-dimethylamine, ethoxy-N,N-diethylamine, thioethane, thioethylamine, thioethyl-N,N-dimethylamine, thioethyl-N,N-diethylamine, thioethyl-N-methyl-N-ethylamine, thioethyl-N-cyanomethylamine, thioethyl-N-ethoxyamine, thioethyl-N-trifluoroamide, thioethyl-N-methylphenol, thioethyl-N-vinyl, thioethyl-N- trimethylthioethyl-N-allyl, thioethyl -N-ethyl ester, thioethyl -N-acetate, thioethyl-N- guanidine, thioethyl-N-trimethylaminocarbonyl, thioethyl-N-diethylurea, thioethyl-N- trimethylpropyl, thioethyl-N-trimethylpropyl, thioethyl-N-hydroxyethyl, thioethyl-N- sulfonate, thioethyl -N-thiophenyl, and thiocyanophenol.

[0087] The terms “aryloxy” and “heteroaryloxy” are used in their conventional sense and refer to those aryl or heteroaryl groups attached to the remainder of the molecule via an oxygen atom.

[0088] The term “aryl” means, unless otherwise stated, a polyunsaturated, aromatic or heteroaromatic ring, substituent that can be a single ring or multiple rings (preferably from 1 to 3 rings), which are fused together or linked covalently with or without an alkyl-hetero chain terminus. The term “heteroaryl” refers to aryl groups (or rings) that contain from one to four heteroatoms selected from N, O, S, Si and B, wherein the nitrogen and sulfur atoms are optionally oxidized, and the nitrogen atom(s) are optionally quatemized. A heteroaryl group can be attached to the remainder of the molecule through a heteroatom. Non-limiting examples of aryl and heteroaryl groups include phenyl, 1 -naphthyl, 2-naphthyl, 4-biphenyl, 1 -pyrrolyl, 2-pyrrolyl, 3 -pyrrolyl, 3-pyrazolyl, 2-imidazolyl, 4-imidazolyl, pyrazinyl, 2- oxazolyl, 4-oxazolyl, 2-phenyl-4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 5- isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, 2- pyridyl, 3-pyridyl, 4-pyridyl, 2-pyrimidyl, 4-pyrimidyl, 5-benzothiazolyl, purinyl, 2- benzimidazolyl, 5-indolyl, 1 -isoquinolyl, 5-isoquinolyl, 2-quinoxalinyl, 5-quinoxalinyl, 3- quinolyl, and 6-quinolyl. Substituents for each of the above noted aryl and heteroaryl ring systems are selected from the group of acceptable substituents described below.

[0089] For brevity, the term “aryl” when used in combination with other terms (e.g., aryloxy, arylthioxy, arylalkyl) includes both aryl and heteroaryl rings as defined above. Thus, the term “arylalkyl” is meant to include those radicals in which an aryl group is attached to an alkyl group (e.g., benzyl, phenethyl, pyridylmethyl and the like) including those alkyl groups in which a carbon atom (e.g., a methylene group) has been replaced by, for example, an oxygen atom (e.g., phenoxymethyl, 2-pyridyloxymethyl, 3-(l-naphthyloxy)propyl, and the like.

[0090] Each of the above terms (e.g., “alkyl,” “heteroalkyl,” “aryl” and “heteroaryl”) are meant to optionally include both substituted and unsubstituted forms of the indicated radical.

[0091] The symbol “R” (and variants thereof, including R’, R”, and R*) is a general abbreviation that represents a substituent group that can selected from H, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted heterocycloalkyl groups, and other substituents as defined herein with respect to R and variants thereof.

[0092] The symbol “(O)” refers to a carbonyl, i.e., =0. Likewise, the symbols “(S)” and “(N)” refer to =S and =N, respectively.

[0093] The terms “halogen” or “halo” refer to fluoro, chloro, bromo, or iodo. “Haloalkyl” refers to one or more halo (e.g., fluoro, difluoro, trifluoro) appended to the parent compound through an alkyl group (e.g., methyl or ethyl).

[0094] “Hydroxy” or “hydroxyl” refers to an -OH group.

[0095] An “amine” or “amino” refers to a group -NH2, wherein none, one, or two of the hydrogen atoms may be replaced by suitable substituents such as alkyl.

[0096] “Thio” or “mercapto” refers to -SH group or to its tautomer =S. “Carboxylate” refers to a salt or ester of a carboxylic acid moiety. “Carboxyalkyl” refers to a carboxylic acid group attached to the principal carbon chain or molecule through an alkyl group. The carboxylic acid group may be present as the free acid, salt, or an ester.

[0097] Unless indicated otherwise, where a chemical group is described by its chemical formula, including a terminal bond moiety indicated by it will be understood that the attachment is read from left to right. For example, — C(O)Ci.6alkyl is attached to the rest of the molecule at the carbonyl end.

[0098] Unless otherwise stated, structures depicted herein are also meant to include all enantiomeric, diastereomeric, and geometric (or conformational) forms of the structure; for example, the R and S configurations for each asymmetric center, (Z) and (E) double bond isomers, and (Z) and (E) conformational isomers. Therefore, single stereochemical isomers as well as enantiomeric, diastereomeric, and geometric (or conformational) mixtures of the present compounds are within the scope of the compounds described herein. Unless otherwise stated, all tautomeric forms of the compounds described herein are within the scope of the compounds described herein. Tautomeric forms include keto-enol tautomers of a compound. In addition, unless otherwise stated, all rotamer forms of the compounds described herein are within the scope of the disclosure. Unless otherwise stated, structures depicted herein are also meant to include compounds that differ only in the presence of one or more isotopically enriched atoms. For example, compounds having the present structures except for the replacement of hydrogen by deuterium or tritium, or the replacement of a carbon by a13C- or14C-enriched carbon are within the scope of this disclosure. Such compounds are useful, for example, as analytical tools or probes in biological assays.

[0099] “Isomers” refers to compounds having the same number and kind of atoms and hence the same molecular weight but differing with respect to the arrangement or configuration of the atoms. It will be understood, however, that some isomers or racemates or other mixtures of isomers may exhibit more activity than others. “Stereoisomers” refers to isomers that differ only in the arrangement of the atoms in space. “Diastereoisomers” refers to stereoisomers that are not mirror images of each other. “Enantiomers” refers to stereoisomers that are non- superimposable mirror images of one another.

[0100] In some embodiments, enantiomeric compounds taught herein may be “enantiomerically pure” isomers that comprise substantially a single enantiomer, for example, greater than or equal to 90%, 92%, 95%, 98%, or 99%, or equal to 100% of a single enantiomer.

[0101] In some embodiments, enantiomeric compounds and intermediates as taught herein may be stereochemically pure. “Stereochemically pure” as used herein means a compound or composition thereof that comprises one stereoisomer of a compound and is substantially free of other stereoisomers of that compound.

[0102] In some embodiments, “7?” and “S” as terms describing isomers are descriptors of the stereochemical configuration at an asymmetrically substituted carbon atom. The designation of an asymmetrically substituted carbon atom as “7?” or “S” is done by application of the Cahn-Ingold-Prelog priority rules, as are well known to those skilled in the art and described in the International Union of Pure and Applied Chemistry (IUPAC) Rules for the Nomenclature of Organic Chemistry. In some examples, the echinocandin-like compounds may be modified such that the hemi-aminal functional group is replaced by either an amide, thioaminal, or aminal. Such a modification can be useful in improving stability and can result in greater whole plant activity.

[0103] Formulations

[0104] The compounds described herein or salts thereof can be provided in a formulation or composition. The echinocandin-like compounds and derivatives can be prepared in formulations or compositions for control of fungal organisms in applications where control of fungal growth is desired including, but not limited to, use as antifungal agents for treatment and / or prevention of plant fungal diseases, disinfectants, and industrial fungicides.

[0105] It is recognized that the compositions described herein can be used in combination with other active ingredients. In this manner, the echinocandin-like compounds can be applied before or after the application of the additional active ingredient. Alternatively, the echinocandin-like compound and the additional active ingredient can be formulated together in a combination formulation. That is, the formulations can include other active ingredients and / or plant or plant product treatment compounds. For use in plant applications, the formulation can optionally include an additional antifungal agent, a contact-acting insecticide and / or a miticide. Further, some of the compositions and formulations can be residual in that they do not easily wash off of the leaves during rain and thus can protect against fungal pests during and after rainy weather. Optionally, the compositions and formulations can exhibit synergy, and in some examples result in better-than-expected results than just the antifungal treatment alone. That is, in some examples, the echinocandin-like compounds described herein when used in combination with an additional active agent, including those listed herein, can show synergistic results when used together. Additionally, in some cases, when used together, less of the echinocandin-like compound and additional active agent may be required to achieve beneficial results. That is, less of the echinocandin-like compound and additional active agent may be required in some examples to control the fungal pathogen. In some other examples, additional active agents can be used in combination with the echinocandin-like compounds described herein and include, without limitation, insecticides, mitocides, ectoparasiticides, as well as other fungicides.

[0106] The formulations or compositions may be liquid or dry compositions. Dry compositions include powders and the like. Such compositions may be used as a seed coating. The compositions can be utilized as liquid concentrates, Ready-To-Use (RTU) liquid sprays, dusts, or solids, depending upon the needs of the user. The formulation chosen will depend on the use of the product. In use, the composition can be applied directly to the fungal pathogen, in the vicinity of the pathogen, and / or in the vicinity of plants and plant products that are to be protected.

[0107] In general, a formulation will include at least one echinocandin-like compound as described herein and one or more agriculturally acceptable adjuvants (also referred to herein as “agriculturally suitable adjuvants”). Agriculturally suitable adjuvants are used to enhance the effectiveness of the compounds of the disclosure and include, but are not limited to, surfactants, emulsifiers, oils, salts, and the like. The adjuvants may be added into the formulation or alternatively can be added separately at the time of application. In some embodiments, wetting agents, emulsifiers, spreaders, and the like may be used in the formulations. Formulations include concentrated versions, in which the present active agent (a compound as described herein) is present in a concentration of from 0.001 to 98.0 percent, with the remaining content being physiologically acceptable carriers. Such formulations, especially those with less than 50 percent of the present compound, can sometimes be used directly, but these formulations can also be diluted with other physiologically acceptable carriers to form more dilute treating formulations. These latter formulations can include the compounds described herein in lesser concentrations of from 0.001 to 0.1 percent.

[0108] The formulations may additionally contain “adjuvant surfactants” to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. These “adjuvant surfactants” may optionally be employed as a component of the formulation or as a tank mix. The amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume (e.g., from 0.05, 0.15, 0.25, 0.35, 0.45, 0.55, 0.65, 0.75, 0.85, or 0.95 percent by volume), based on a spray -volume of water, preferably 0.05 to 0.5 volume percent (e.g., from 0.15, 0.25, 0.35, or 0.45 volume percent). Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulphosuccinic acids, ethoxylated organosilicones, ethoxylated fatty amines, blends of surfactants with mineral or vegetable oils, crop oil concentrate (mineral oil (85%) + emulsifiers (15%)); nonylphenol ethoxylate; benzylcocoalkyldimethyl quaternary ammonium salt; blend of petroleum hydrocarbon, alkyl esters, organic acid, and anionic surfactant; C9- Cu alkylpolyglycoside; phosphated alcohol ethoxylate; natural primary alcohol (C12- Ci6) ethoxylate; di -sec-butylphenol EO-PO block copolymer; polysiloxanemethyl cap; nonylphenol ethoxylate + urea ammonium nitrrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. The formulations may also include oil-in-water emulsions such as those disclosed in U.S. Patent Application Serial No. 11 / 495,228, the disclosure of which is expressly incorporated by reference herein.

[0109] “Surfactants” comprise typically about 0.5% to about 10% of the wettable powder. “Surfactants” include sulfonated lignins, condensed naphthal ene-sulfonates, the naphthalenesulfonates, alkyl-benenesulfonates, alkysulfonates or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof.

[0110] Emulsifiable concentrates of the derivatives described herein typically consist of about 50 to about 500 grams of the echinocandin-like compound per liter of liquid, equivalent to about 10% to about 50%, dissolved in an “inert carrier solvent” which is a mixture of a water immiscible organic solvent and emulsifiers.

[0111] Representative organic solvents which may be employed in preparing the emulsifiable concentrates of the compounds of the present disclosure are the aromatic liquids such as xylene, propyl benzene fractions; or mixed naphthalene fractions, mineral oils, substituted aromatic organic liquids such as dioctyl phthalate; kerosene; dialkyl amides of various fatty acids, particularly the dimethyl amides of fatty glycols and glycol derivatives such as the n- butyl ether, ethyl ether or methyl ether of diethylene glycol, the methyl ether of triethylene glycol, petroleum fractions or hydrocarbons such as mineral oil, aromatic solvents, paraffinic oils, and the like; terpenic solvents, rosin derivatives, aliphatic ketones such as cyclohexanone, complex aliphatic and aromatic alcohols such as 2-ethoxyethanol, vegetable oils such as soy bean oil, rape seed oil, olive oil, castor oil, sunflower seed oil, coconut oil, com oil, cotton seed oil, linseed oil, palm oil, peanut oil, safflower oil, sesame oil, tung oil and the like; esters of the above vegetable oils; and the like. Mixtures of two or more organic liquids may also be employed in the preparation of the emulsifiable concentrate. Organic liquids include xylene, and propyl benzene fractions, with xylene being most preferred in some cases. Surface-active dispersing agents are typically employed in liquid formulations and in an amount of from 0.1 to 20 percent by weight based on the combined weight of the dispersing agent with one or more of the compounds. “Emulsifiers” for emulsifiable concentrates are typically mixed ionic and / or nonionic surfactants such as those mentioned herein or their equivalents. Examples of nonionic emulsifiers useful in preparing the emulsifiable concentrates include the polyalkylene glycol ethers and condensation products of alkyl and aryl phenols, aliphatic alcohols, aliphatic amines or fatty acids with ethylene oxide, propylene oxides such as the ethoxylated alkyl phenols and carboxylic esters solubilized with the polyol or polyoxyalkylene. Cationic emulsifiers include quaternary ammonium compounds and fatty amine salts. Anionic emulsifiers include the oil soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oilsoluble salts or sulfated polyglycol ethers and appropriate salts of phosphated- polyglycol ether.

[0112] Agricultural compositions can be prepared according to the procedures and formulas which are conventional in the agricultural or pest control industry. The compositions may be concentrated and dispersed in water or may be used in the form of a dust, bait or granular formulation. The dispersions are typically aqueous suspensions or emulsions prepared from concentrated formulations of the compounds. The water-soluble or water-suspension or emulsifiable formulations are either solids, wettable powders, precipitated flowables, or liquids, known as emulsifiable concentrates, aqueous suspensions or suspension concentrates. As will be readily appreciated, any material to which these compounds may be added may be used, provided it yields the desired utility without significant interference with the activity of these compounds as antifungal agents.

[0113] Dusts containing the compounds of the present disclosure may be prepared by intimately mixing one or more of the compounds in powdered form with a suitable dusty agricultural carrier, such as, for example, kaolin clay, ground volcanic rock, and the like. Dusts can suitably contain from about 1 to about 10 weight percent of the compounds, based on the total weight of the dust.

[0114] Wettable powders may be agglomerated or compacted to form water dispersible granules. These granules include mixtures of compounds, inert carriers suitable for granular applications and surfactants. The concentration of the compound is typically from about 0.1% to about 90% by weight (e.g., from about 0.5%, 2.5%, 5%, 10%, 20%, 30%, 40%, 50%, 60%, 70%, or 80% by weight). The “inert carrier suitable for granular applications” is typically prophyllite, talc, chalk, gypsum, Fuller's earth, bentonite, attapulgite, starch, casein, gluten, montmorillonite clays, diatomaceous earths, purified silicates or the like. In such operations, the finely divided carrier and surfactants are typically blended with the compound(s) and milled.

[0115] “Aqueous suspensions” may be prepared containing water-insoluble echinocandinlike compounds described herein, where the compounds are dispersed in an aqueous vehicle at a concentration typically in the range of from about 5% to about 50% by weight (e.g., from about 10%, 15%, 20%, 25%, 20%, 35%, 40%, or 45% by weight). The suspensions are prepared by finely grinding the compound and vigorously mixing it into a vehicle of water, surfactants, and dispersants. Inert ingredients such as inorganic salts and synthetic or natural gums may also be employed to increase the density and / or viscosity of the aqueous vehicle as is desired.

[0116] “Precipitated flowables” may be prepared by dissolving at least one echinocandin-like compound described herein in a water-miscible solvent and surfactants or surface-active polymers. When these formulations are mixed with water, the active echinocandin-like molecule precipitates with the surfactant controlling the size of the resulting micro-crystalline precipitate. The size of the crystal can be controlled through the selection of specific polymer and surfactant mixtures.

[0117] The echinocandin-like compounds or combination thereof may also be applied as a granular composition that is applied to the soil. The granular composition typically contains from about 0.5% to about 10% by weight of the compound (e.g., from about 1.0%, 1.5%, 2.0%, 2.5%, 3.0%, 3.5%, 4.0%, 4.5%, 5.0%, 5.5%, 6.0%, 6.5%, 7.0%, 7.5%, 8.0%, 8.5%, 9.0%, or 9.5% by weight of the compound). The echinocandin-like compounds can be dispersed in an “inert carrier suitable for granular applications” which is typically clay or an equivalent substance. Generally, granular compositions are prepared by dissolving the compounds described herein in a suitable solvent and applying it to a granular carrier which has been pre-formed to the desirable particle size. The particle size is typically from about 0.5 mm to 3 mm (e.g., from about 1 mm to 3 mm , 1.5 mm to 3 mm , 2 mm to 3 mm , or 2.5 mm to 3 mm). The granular compositions may also be prepared by forming a dough or paste of the “inert carrier suitable for granular applications” and compound, drying the combined mixture, and crushing the dough or paste to the desired particle size.

[0118] The echinocandin-like compounds may also be combined with an appropriate organic solvent. The organic solvent is typically a blend of petroleum oils that is widely used in the agricultural industry. These combinations are typically used as a spray. More typically, the echinocandin-like compounds are applied as a dispersion in a liquid carrier, where the liquid carrier is water. The compounds may also be applied in the form of an aerosol composition. The compound is dissolved in an “inert carrier suitable for aerosol applications”, which is a pressure-generating propellant mixture. The aerosol composition is packaged in a container, where the mixture is dispersed through an atomizing valve. Propellant mixtures contain either low-boiling halocarbons, which may be mixed with organic solvents or aqueous suspensions pressurized with inert gases or gaseous hydrocarbons.

[0119] The formulations may optionally include combinations that contain other pesticidal compounds. Such additional pesticidal compounds may be fungicides, insecticides, herbicides, nematocides, miticides, arthropodicides, bactericides or combinations thereof that are compatible with the compounds of the present disclosure in the medium selected for application, and not antagonistic to the activity of the present compounds. Accordingly, in such embodiments, the other pesticidal compound is employed as a supplemental toxicant for the same or for a different pesticidal use. The compounds disclosed herein and the pesticidal compound in the combination can generally be present in a weight ratio of from 1 : 100, 1 :50, 1 :25, 1 : 10, 1 :5, 1 : 1, 5:1, 10: 1, 25: 1, 50: 1 to 100:1.

[0120] The compounds of the present disclosure may also be combined with other fungicides to form fungicidal mixtures and synergistic mixtures thereof. The fungicidal compounds of the present disclosure are often applied in conjunction with one or more other fungicides to control a wider variety of undesirable diseases. When used in conjunction with other fungicide(s), the currently disclosed echinocandin-like compounds may be formulated with the other fungicide(s), tank-mixed with the other fungicide(s) or applied sequentially with the other fungicide(s). Possible fungicides that can be used in combination with the methods and compositions disclosed herein include, but are not limited to, aliphatic nitrogen fungicides (butylamine, cymoxanil, dodicin, dodine, guazatine, iminoctadine); amide fungicides (benzovindiflupyr, carpropamid, chloraniformethan, cyflufenamid, diclocymet, octandimoxystrobin, fenaminstrobin, fenoxanil, flumetover, furametpyr, isofetamid, isopyrazam, mandestrobin, mandipropamid, metominostrobin, orysastrobin, penthiopyrad, prochloraz, quinazamid, silthiofam, triforine); acylamino acid fungicides (benalaxyl, benalaxyl-M, furalaxyl, mefenoxam, metalaxyl, metalaxyl-M, pefurazoate, valifenalate); aminonicotinate fungicides (aminopyrifen); anilide fungicides (benalaxyl, benalaxyl-M, bixafen, boscalid, carboxin, fenhexamid, fluxapyroxad, isotianil, metalaxyl, metalaxyl-M, metsulfovax, ofurace, oxadixyl, oxycarboxin, penflufen, pyracarbolid, sedaxane, thifluzamide, tiadinil, vanguard); benzanilide fungicides (benodanil, flutolanil, mebenil, mepronil, salicylanilide, tecloftalam); furanilide fungicides (fenfuram, furalaxyl, furcarbanil, methfuroxam); sulfonanilide fungicides (flusulfamide); benzamide fungicides (benzohydroxamic acid, fluopicolide, fluopimomide, fluopyram, tioxymid, trichlamide, zarilamid, zoxamide); furamide fungicides (cyclafuramid, furmecyclox); phenylsulfamide fungicides (dichlofluanid, tolylfluanid); sulfonamide fungicides (amisulbrom, cyazofamid); valinamide fungicides (benthiavalicarb, iprovalicarb); antibiotic fungicides (aureofungin, blasticidin-S, cycloheximide, griseofulvin, kasugamycin, moroxydine, natamycin, polyoxins, polyoxorim, streptomycin, validamycin); strobilurin fungicides (fluoxastrobin, mandestrobin); methoxyacrylate strobilurin fungicides (azoxystrobin, bifujunzhi, coumethoxystrobin, coumoxystrobin, enoxastrobin, flufenoxystrobin, jiaxiangjunzhi, picoxystrobin, pyraoxystrobin); methoxycarbanilate strobilurin fungicides (pyraclostrobin, pyrametostrobin, triclopyricarb); methoxyiminoacetamide strobilurin fungicides (dimoxystrobin, fenaminstrobin, metominostrobin, orysastrobin); methoxyiminoacetate strobilurin fungicides (kresoxim-methyl, trifloxystrobin); aromatic fungicides (biphenyl, chlorodinitronaphthalenes, chloroneb, chlorothalonil, cresol, dicloran, fenjuntong, hexachlorobenzene, pentachlorophenol, quintozene, sodium pentachlorophenoxide, tecnazene, trichlorotrinitrobenzenes); arsenical fungicides (asomate, urbacide); aryl phenyl ketone fungicides (metrafenone, pyriofenone); benzimidazole fungicides (albendazole, benomyl, carbendazim, chlorfenazole, cypendazole, debacarb, fuberidazole, mecarbinzid, rabenzazole, thiabendazole); benzimidazole precursor fungicides (furophanate, thiophanate, thiophanate-methyl); benzothiazole fungicides (bentaluron, benthiavalicarb, benthiazole, chlobenthiazone, probenazole); botanical fungicides (allicin, berberine, carvacrol, carvone, osthol, sanguinarine, santonin); bridged diphenyl fungicides (bithionol, dichlorophen, diphenylamine, hexachlorophene, parinol); carbamate fungicides (benthiavalicarb, furophanate, iodocarb, iprovalicarb, picarbutrazox, propamocarb, prothiocarb, pyribencarb, thiophanate, thiophanate-methyl, tolprocarb); benzimidazolyl carbamate fungicides (albendazole, benomyl, carbendazim, cypendazole, debacarb, mecarbinzid); carbanilate fungicides (diethofencarb, pyraclostrobin, pyrametostrobin, triclopyricarb); conazole fungicides, conazole fungicides (imidazoles) (climbazole, clotrimazole, imazalil, oxpoconazole, pefurazoate prochloraz, triflumizole); conazole fungicides (triazoles) (azaconazole, bromuconazole, cyproconazole, diclobutrazol, difenoconazole, diniconazole, diniconazole-M, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, furconazole, furconazole-cis, hexaconazole, imibenconazole, ipconazole, metconazole, myclobutanil, penconazole, propiconazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, triti conazole, uniconazole, uniconazole-P); copper fungicides (acypetacs-copper, Bordeaux mixture, Burgundy mixture, Cheshunt mixture, copper acetate, copper carbonate, basic, copper hydroxide, copper naphthenate, copper octanoate, copper oleate, copper oxychloride, copper silicate, copper sulfate, copper sulfate, basic, copper zinc chromate, cufraneb, cuprobam, cuprous oxide, mancopper, oxine-copper, saisentong, thiodiazole-copper); cyanoacrylate fungicides (benzamacril, phenamacril); dicarboximide fungicides (famoxadone, fluoroimide); dichlorophenyl dicarboximide fungicides (chlozolinate, dichlozoline, dimethachlone, iprodione, isovaledione, myclozolin, procymidone, vinclozolin); phthalimide fungicides (captafol, captan, ditalimfos, folpet, thiochlorfenphim); dinitrophenol fungicides (binapacryl, dinobuton, dinocap, dinocap-4, dinocap-6, meptyldinocap, dinocton, dinopenton, dinosulfon, dinoterbon, DNOC); dithiocarbamate fungicides (amobam, asomate, azithiram, carbamorph, cufraneb, cuprobam, disulfiram, ferbam, metam, nabam, tecoram, thiram, urbacide, ziram); cyclic dithiocarbamate fungicides (dazomet, etem, milneb); polymeric dithiocarbamate fungicides (mancopper, mancozeb, maneb, metiram, polycarbamate, propineb, zineb); dithiolane fungicides (isoprothiolane, saijunmao); fumigant fungicides (carbon disulfide, cyanogen, dithioether, methyl bromide, methyl iodide, sodium tetrathiocarbonate); hydrazide fungicides (benquinox, saijunmao); imidazole fungicides (cyazofamid, fenamidone, fenapanil, glyodin, iprodione, isovaledione, pefurazoate, triazoxide); conazole fungicides (imidazoles) (climbazole, clotrimazole, imazalil, oxpoconazole, prochloraz, triflumizole); inorganic fungicides (potassium azide, potassium thiocyanate, sodium azide, sulfur, see also copper fungicides, see also inorganic mercury fungicides); mercury fungicides; inorganic mercury fungicides (mercuric chloride, mercuric oxide, mercurous chloride); organomercury fungicides ((3-ethoxypropyl)mercury bromide, ethylmercury acetate, ethylmercury bromide, ethylmercury chloride, ethylmercury 2,3 -dihydroxypropyl mercaptide, ethylmercury phosphate, 7V-(ethylmercury)- / ?-toluenesulphonanilide, hydrargaphen, 2- methoxyethylmercury chloride, methylmercury benzoate, methylmercury dicyandiamide, methylmercury pentachlorophenoxide, 8-phenylmercurioxyquinoline, phenylmercuriurea, phenylmercury acetate, phenylmercury chloride, phenylmercury derivative of pyrocatechol, phenylmercury nitrate, phenylmercury salicylate, thiomersal, tolylmercury acetate); morpholine fungicides (aldimorph, benzamorf, carbamorph, dimethomorph, dodemorph, fenpropimorph, flumorph, tridemorph); organophosphorus fungicides (ampropylfos, ditalimfos, EBP, edifenphos, fosetyl, hexylthiofos, inezin, iprobenfos, izopamfos, kejunlin, phosdiphen, pyrazophos, tolclofos-methyl, triamiphos); organotin fungicides (decafentin, fentin, tributyltin oxide); oxathiin fungicides (carboxin, oxycarboxin); oxazole fungicides (chlozolinate, dichlozoline, drazoxolon, famoxadone, fluoxapiprolin; hymexazol, metazoxolon, myclozolin, oxadixyl, oxathiapiprolin, pyrisoxazole, vinclozolin); picolinamide fungicides (fenpicoxamid, florylpicoxamid); polysulfide fungicides (barium polysulfide, calcium polysulfide, potassium polysulfide, sodium polysulfide); pyrazine fungicides (pyraziflumid); pyrazole fungicides (benzovindiflupyr, bixafen, fenpyrazamine, fluindapyr, fluxapyroxad, furametpyr, inpyrfluxam, isopyrazam, isofluocyram, oxathiapiprolin, penflufen, penthiopyrad, pydiflumetofen, pyraclostrobin, pyrametostrobin, pyraoxystrobin, pyrapropoyne, rabenzazole, sedaxane, tolfenpyrad); pyridazine fungicides (pyridachlometyl); pyridine fungicides (boscalid, buthiobate, dipyrithione, fluazinam, fluopicolide, fluopyram, parinol, picarbutrazox, pyribencarb, pyridinitril, pyrifenox, pyrisoxazole, pyroxychlor, pyroxyfur, triclopyricarb); pyrimidine fungicides (bupirimate, diflumetorim, dimethirimol, ethirimol, fenarimol, ferimzone, nuarimol, triarimol); anilinopyrimidine fungicides (cyprodinil, mepanipyrim, pyrimethanil); pyrrole fungicides (dimetachlone, fenpiclonil, fludioxonil, fluoroimide); quaternary ammonium fungicides (berberine, sanguinarine); quinazoline fungicides (fenazaquin); quinoline fungicides (ethoxyquin, halacrinate, 8- hydroxyquinoline sulfate, ipflufenoquin, quinacetol, quinoxyfen, tebufloquin); quinone fungicides (chloranil, dichlone, dithianon); quinoxaline fungicides (chinomethionat, chlorquinox, thioquinox); tetrazolinone fungicides (metyltetraprole)amisulbrom thiadiazole fungicides (etridiazole, saisentong, thiodiazole-copper, zinc thiazole); thiazole fungicides (ethaboxam, isotianil, metsulfovax, octhilinone, oxathiapiprolin, thiabendazole, thifluzamide); thiazolidine fungicides (flutianil, thiadifluor); thiocarbamate fungicides (methasulfocarb, prothiocarb, pyributicarb); thiophene fungicides (ethaboxam, isofetamid, silthiofam); triazine fungicides (anilazine); triazole fungicides (amisulbrom, bitertanol, fluotrimazole, triazbutil); conazole fungicides (triazoles) (azaconazole, bromuconazole, cy proconazole, diclobutrazol, difenoconazole, diniconazole, diniconazole-M, epoxiconazole, etaconazole, fenbuconazole, fluquinconazole, flusilazole, flutriafol, furconazole, furconazole- cis, hexaconazole, huanjunzuo, imibenconazole, ipconazole, ipfentrifluconazole, mefentrifluconazole; metconazole, myclobutanil, penconazole, propi conazole, prothioconazole, quinconazole, simeconazole, tebuconazole, tetraconazole, triadimefon, triadimenol, tri ti conazole, uniconazole, uniconazole-P); triazolopyrimidine fungicides (ametoctradin); urea fungicides (bentaluron, pencycuron, quinazamid); zinc fungicides (acypetacs-zinc, copper zinc chromate, cufraneb, mancozeb, metiram, polycarbamate, polyoxorim-zinc, propineb, zinc naphthenate, zinc thiazole, zinc trichlorophenoxide, zineb, ziram); unclassified fungicides (acibenzolar, acypetacs, allyl alcohol, benzalkonium chloride, bethoxazin, bromothalonil, chitosan, chloropicrin, DBCP, dehydroacetic acid, dichlobentiazox, diclomezine, diethyl pyrocarbonate, dipymetitrone, ethylicin, fenaminosulf, fenitropan, fenpropidin, formaldehyde, furfural, hexachlorobutadiene, methyl isothiocyanate, nitrostyrene, nitrothal -isopropyl, OCH, pentachlorophenyl laurate, 2-phenylphenol, phthalide, piperalin, propamidine, proquinazid, pyroquilon, quinofumelin, sodium orthophenylphenoxide, spiroxamine, sultropen, thicyofen, tricyclazole).

[0121] The following general treatment methods are preferably suitable for carrying out the seed treatment, or plant propagation material treatment, according to the disclosure: dry treatments (preferably with addition of adhesion promoters such as, for example, liquid paraffin or talc), and, if appropriate, colorants, slurry treatments (preferably with addition of wetters, dispersants, emulsifiers, adhesives, inert fillers and colorants), aqueous liquid treatments (preferably with addition of emulsifiers, dispersants, thickeners, antifreeze agents, polymers, adhesives, and colorants), solvent-based liquid treatments (with addition of solvents and colorants), and emulsion treatments (with addition of emulsifiers, solvents, and colorants).

[0122] The total active echinocandin-like compounds in the treatment formulations preferably amount to 0.01% to 80% by weight. For example, the total active echinocandin compound can amount to 0.01% by weight, 0.05% by weight, 0.1% by weight, 0.5% by weight, 1% by weight, 5% by weight, 10% by weight, 20% by weight, 30% by weight, 40% by weight, 50% by weight, 60% by weight, 70% by weight, or 80% by weight. Generally, about 1 g to about 300 g of the composition comprising the echinocandin-like compound or compounds are applied to every 100 kg of seed or plant propagation material in the form of a treatment (e.g., from about 5 g to 200 g, 10 g to 100 g, or from 25 g to 50 g of the composition is applied to every 100 kg of seed or plant propagation material).

[0123] The echinocandin-like compounds, combinations and formulations can be used for treating soil, for treating seed or plant propagation material, and for drenching and irrigating plants. The following exemplary types of seed and plant propagation material can be treated: maize, cereals (such as, for example, wheat, barley, oats, rye), rice, seed potatoes, cotton, oilseed rape, sunflower, beet (such as, for example, sugar beet), vegetable seed (such as, for example, onion, cabbage, tomato), (fodder) legumes, peanuts, soya, sorghum, and the like.

[0124] In some examples, it is advantageous to apply granules comprising the active compound(s) described herein into or onto the soil. Examples of suitable applications include broadcast, band, furrow and planting-hole application.

[0125] In some other examples, it is particularly advantageous to emulsify or dissolve the antifungal compounds described herein or their salts in water and to use this for irrigating the plants. Examples of suitable applications are spraying onto the soil, drenching, i.e., irrigating the plants with active-compound-containing solutions, and drip irrigation, and also use in hydroponic systems, in particular in the production of vegetables and ornamentals. Fungicidal Target Species

[0126] The compositions can be used to treat and control plant disease in any plant of interest. Particular plant species include, but are not limited to, com (Zea mays), Brassica sp. (e.g., B. napus, B. rapa, B.juncea), particularly those Brassica species useful as sources of seed oil, alfalfa (Medicago sativa), rice (Oryza sativa), rye (Secale cereale), sorghum (Sorghum bicolor, Sorghum vulgare), millet (e.g., pearl millet (Pennisetum glaucum), proso millet (Panicum miliaceum), foxtail millet (Setaria italica), finger millet (Eleusine coracana)), sunflower (Helianthus annuus), safflower (Carthamus tinctorius), wheat (Triticum aestivum), soybean (Glycine max), tobacco (Nicotiana tabacum), potato (Solanum tuberosum), peanuts (Arachis hypogaea), cotton (Gossypium barbadense, Gossypium hirsutum), sweet potato (Ipomoea batatus), cassava (Manihot esculenta), coffee (Coffea spp.), coconut (Cocos nucifera), pineapple (Ananas comosus), citrus trees (Citrus spp.), cocoa (Theobroma cacao), tea (Camellia sinensis), banana (Musa spp.), avocado (Persea americana), fig (Ficus casica), guava (Psidium guajava), mango (Mangifera indica), olive (Olea europaea), papaya (Carica papaya), grape (Vitus spp.), strawberry (Fragaria x ananassa), cherry (Prunus spp.), apple (Malus domestica), orange (Citrus x sinensis) cashew (Anacardium occidentale), macadamia (Macadamia integrifolia), almond (Primus amygdalus), sugar beets (Beta vulgaris), sugarcane (Saccharum spp.), oats, barley, vegetables, ornamentals, and conifers.

[0127] Vegetables include tomatoes (Lycopersicon esculentum), lettuce (e.g., Lactuca saliva), green beans (Phaseolus vulgaris), lima beans (Phaseolus limensis), peas (Lathyrus spp.), and members of the genus Cucumis such as cucumber (C. sativus), cantaloupe (C. cantalupensis), and musk melon (C. melo). Ornamentals include azalea (Rhododendron spp.), hydrangea (Macrophylla hydrangea), hibiscus (Hibiscus rosasanensis), roses (Rosa spp.), tulips (Tulipa spp.), daffodils (Narcissus spp.), petunias (Petunia hybrida), carnation (Dianthus caryophyllus), poinsettia (Euphorbia pulcherrima), and chrysanthemum.

[0128] Other plants include, but are not limited to flax, vine and various fruits and vegetables of various botanical taxa such as Rosaceae sp. (for instance pip fruit such as apples and pears, but also stone fruit such as apricots, cherries, almonds and peaches, berry fruits such as strawberries), Ribesioidae sp., Juglandaceae sp., Betulaceae sp., Anacardiaceae sp., Fagaceae sp., Moraceae sp., Oleaceae sp., Actinidaceae sp., Lauraceae sp., Musaceae sp. (for instance banana trees and plantings), Rubiaceae sp. (for instance coffee), Theaceae sp., Sterculiceae sp., Rutaceae sp. (for instance lemons, oranges and grapefruit) ; Solanaceae sp. (for instance tomatoes, potatoes, peppers, eggplant), Liliaceae sp., Compositiae sp. (for instance lettuce, artichoke and chicory - including root chicory, endive or common chicory), Umbelliferae sp. (for instance carrot, parsley, celery and celeriac), Cucurbitaceae sp. (for instance cucumber- including pickling cucumber, squash, watermelon, gourds and melons), Alliaceae sp. (for instance onions and leek), Cruciferae sp. (for instance white cabbage, red cabbage, broccoli, cauliflower, brussel sprouts, pak choi, kohlrabi, radish, horseradish, cress, Chinese cabbage), Leguminosae sp. (for instance peanuts, peas and beans - such as climbing beans and broad beans), Chenopodiaceae sp. (for instance mangold, spinach beet, spinach, beetroots), Malvaceae (for instance okra), Asparagaceae (for instance asparagus); horticultural and forest crops; ornamental plants; as well as genetically modified homologues of these crops. In specific embodiments, the plants can be crop plants (for example, com, alfalfa, sunflower, Brassica, soybean, cotton, safflower, peanut, sorghum, wheat, millet, tobacco, etc.). In other embodiments, com and soybean plants are optimal, and in yet other embodiments, com plants are optimal.

[0129] Other plants of interest include grain plants that provide seeds of interest, oil-seed plants, and leguminous plants. Seeds of interest include grain seeds, such as com, wheat, barley, rice, sorghum, rye, etc. Oil-seed plants include cotton, soybean, safflower, sunflower, Brassica, maize, alfalfa, palm, coconut, etc. Leguminous plants include beans, peas, and dry pulses. Beans include guar, locust bean, fenugreek, soybean, garden beans, cowpea, mungbean, lima bean, fava bean, lentils, chickpea, etc.

[0130] Wild plant species and plant cultivars, or those obtained by conventional biological breeding methods, such as crossing or protoplast fusion, and parts thereof, can be treated by the compositions as described herein. Transgenic plants and plant cultivars obtained by genetic engineering methods, if appropriate in combination with conventional methods (Genetically Modified Organisms), and parts thereof can be treated by the above disclosed methods. Preferably, plants of the plant cultivars which are commercially available or are in use are treated in accordance with the disclosure. Plant cultivars are understood to mean plants which have new properties (“traits”) and have been obtained by conventional breeding, by mutagenesis or by recombinant DNA techniques. They can be cultivars, varieties, bio- or genotypes.

[0131] Plant Diseases

[0132] Plant diseases which can be treated or reduced or prevented by the compositions and / or methods described herein include, but are not limited to, plant diseases caused by fungi, viruses or viroids, protozoa, bacteria, and the like. Examples of fungal plant diseases include, but are not limited to Alternaria leaf spots, Alternaria fruit and tuber rots, Anthracnose leaf spots, anthracnose fruit and tuber rots, Asochyta blights, Asian soybean rust (ASR), Bakanae (foolish seedling) diseases, belly rots, black rot of fruits, black rust, black scurf, black sigatoka leaf streak (BLS), brown patch, brown rot of fruits, brown rust, bunts, cankers, crown rot, damping off complexes, dollar spot, downy mildews, ear and panicle rots, early blight, frogeye leaf spot diseases, Fusarium head blight, gray molds, head blights, late blight, leaf blisters, leaf blotches, leaf curls, leaf spots, mummy berry diseases, needle cast diseases, Penicillium decays, Phomopsis diseases, Phytophthora fruit rots, powdery mildews, Pythium blights, rice blast, root rots, rust diseases, scab diseases, scald diseases, Septoria leaf and glume blotch, Septoria leaf spots, sheath blights, smuts, snow molds, stalk rots, stem rots, stripe diseases, stripe rust, sudden death syndrome (SDS), take-all diseases, tan spots, target spots, vascular streak diseases, Verticillium wilt, wilt diseases, wheat rust, white mold, yellow rust, and yellow sigatoka. The compositions and methods described herein can be used to control at least one or more fungal pathogens from the following classes: Ascomycota; Basidiomycota; Deuteromycota (fungi imperfecti); Oomycota; and Zygomycota. Among the diseases of plants or crops that can potentially be treated, reduced, prevented, or controlled by the compositions and methods described herein include: powdery mildew diseases caused by different species of fungi in the order Erysiphales (Erysiphe cichoracearum (Golovinomyces cichoracearum)) with Podosphaera xanthii (Sphaerotheca fuliginea) being the most commonly reported cause; Blumeria diseases, caused for example by Blumeria graminis: Leveillula diseases, caused for example by Leveillula taurica (Oidiopsis sicula): Podosphaera diseases, caused for example by Podosphaera macularis and P. leiicolricha: Sphaerotheca diseases, caused for example by Sphaerotheca fuliginea: Uncinula diseases, caused for example by Uncinula necalor: rust diseases such as: Gymnosporangium diseases, caused for example by Gymnosporangium juniperi-virginianae and G. sahinae: Hemileia diseases, caused for example by Hemileia coffeicola and H. vaslalrix: Phakopsora diseases, caused for example by Phakopsora pachyrhizi or P. meibomiae ; Puccinia diseases, caused for example by Puccinia recondila, P. recondita f.sp. tritici, P. graminis, P. striiformis or P. Irilicina: Uromyces diseases, caused for example by Uromyces appendiculalus: oomycete diseases such as: Albugo diseases, caused for example by Albugo Candida or A. occidenlalis: Bremia diseases, caused for example by Bremia laclucae: Hyaloperonospora diseases cause by Hyaloperonospora parasitica; Peronospora diseases, caused for example by Peronospora manshurica, P. pisi or P. viciae; Phytophthora diseases, caused for example by Phytophthora capcisi, P. infestans, or P. tropicalis; Plasmopara diseases, caused for example by Plasmopara nivea or P. viticola; Pseudoperonospora diseases, caused for example by Pseudoperonospora cubensis or P. humuli: Pythium diseases, caused for example by Pythium irregulare or P. ullimum: Sclerophthora diseases, caused for example by Sclerophthora macrospora leafspot, leaf blotch and leaf blight diseases such as: Alternaria diseases, caused for example by Alternaria alternata, A. solani, or A. Irilicina: Apiognomonia diseases, caused for example by Apiognomonia errabunda; Ascochyta dieseases, caused for example by Ascochyta graminea, A. tritici, Didymella rabiei (Phyllosticta cicerina), or Mycosphaerella pinodes; Bipolaris diseases, caused for example by Bipolaris maydis (Cochliobolus heterostr ophus), B. oryzae (Cochliobolus miyabeanus), or B. zeicola (Cochliobolus carbonum): Botryosphaeria diseases, caused for example by Botryosphaeria obtuse,' Botrytis diseases, caused for example by Botrytis cinerea; Cercospora diseases, caused for example by Cercospora arachidicola, C. beticola, C. kikuchii, C. musae, C. sojina, or C. zeae-maydis: Cercosporidium diseases, caused for example by Cercosporidium henningsii or C. personatum; Cladiosporum diseases, caused for example by Cladiosporium caryigenum or C. ciiciimerinum: Clarireedia diseases, caused for example by Clarireedia homoeocarpa (Sclerotinia homoeocarpa): Cochliobolus diseases, caused for example by Cochliobolus sativus (Conidiaform: Drechslera, Syn: Helminlhosporium): Colletotrichum diseases, caused for example by Colletotrichum acutamtum, C. cereale, C. gloeosporiodes, C. gossypii, C. lindemuthanium, C. obiculare, or C. sublineola: Coniothyrium diseases, caused for example by Coniothyrium glycines,' Corticum diseases, caused for example by Corticum penicillatum; Corynespora diseases, caused for example by Corynespora cassiicola; Cycloconium diseases, caused for example by Cycloconium oleaginum (Spilocaea oleaginea); Diaporthe diseases, caused for example by Diaporthe citri; Elsinoe diseases, caused for example by Elsinoe ampelina, E. fawcettii, or E. veneta, Gloeosporium diseases, caused for example by Gloeosporium cyclaminis; Glomerella diseases, caused for example by Glomerella cingulata, G. gossypii, or G. graminicola; Guignardia diseases, caused for example by Guignardia bidwelli; Leptosphaeria diseases, caused for example by Leptosphaeria coniothyrium, L. maculans, or L. nodorunr, Magnaporthe diseases, caused for example by Magnaporthe grisea (Pyricularia oryzae), M. poae, or M. salvinii; Michrodochium diseases, caused for example by Michrodochium panattonianunr, Monographella disease, caused for example by Monographella albescens; Mycosphaerella diseases, caused for example by Mycosphaerella aerola, M. arachidicola, M. berkeleyi, M. eumusae, M. fijiensis (Pseudocercospora fijiensis), M. graminicola, M. musicola; Phaeosphaeria diseases, caused for example by Phaeosphaeria nodorum (Parastagonospora nodorum); Phomopsis diseases, caused for example by Phomopsis obscurans; Phytophthora diseases, caused for example by Phytophthora infestans; Plasmopora disease, caused for example by Plasmopora halstedii or P. lactucae- radicis; Pseudocercospora diseases, caused for example by Pseudocercospora cruenta or P. fijiensis; Pseudoper onospora diseases, caused for example by Pseudoper onospora cannabina; Pyrenophora diseases, caused for example by Pyrenophora teres, or P. tritici- repentis; Ramularia diseases, caused for example by Ramularia areola, or R. collocygni; Rhynchosporium diseases, caused for example by Rhynchosporium secalis; Septoria diseases, caused for example by Septoria apii, S. glycines, S. lycopercisi, S. secalis, or S. tritici; Stemphylium diseases, cause for example by Stemphylium solani; Tapesia diseases, caused for example by Tapesia acuformis (Pseudocercosporella herpolrichoides) or T. yallundae: Typhula diseases, caused for example by Typhula incarnata; Venturia diseases, caused for example by Venturia carpophila, V.effusa, V. inaequalis, V. oleaginea (Spilocaea oleaginea), or V. pyrina; Zymoseptoria dieseases, caused for example by Zymoseptoria tritici or Z. passerinii; root, sheath and stem diseases such as: Agroathelia diseases, caused for example by Agroathelia rolfsii (Athelia rolfsii); Ceratobasidium diseases, cause for example by Ceratobasidium cereale or C. setariae; Corticium diseases, caused for example by Corticium graminearum (Ceratobasidium cornigerum); Diaporthe diseases, caused for example by Diaporthe helianthi or D. phaseolorum; Didymella diseases, caused for example by Didymella bryoniae; Fusarium diseases, caused for example by Fusarium graminicola or F. oxysporum; Gaeumannomyces diseases, caused for example by Gaeumannomyces graminis or G. tritici; Helminthosporium disease, caused for example by Helminthosporium oryzae; Leptosphaeria diseases, caused for example bye Leptosphaeria maculans; Magnaporthe diseases, caused for example by Magnaporthe salvinii; Phoma diseases, caused for example by Phoma lingam; Phomopsis diseases, caused for example by Phomopsis asparagi, P. helianthi, or P. sojae; Phytophthora diseases, caused for example by Phytophthora capsici, P. nicotianae, or P. sojae; Rhizoctonia diseases, caused for example by Rhizoctonia cerealis, R. noxia, R oryzae-sativae, or R solani; Sarocladium diseases caused for example by Sarocladium oryzae; Sclerophthora diseases, caused for example by Sclerophthora macrospora; Sclerotinia diseases, caused for example by Sclerotinia sclerotiorum;

[0133] Sclerotium diseases caused for example by Sclerotium oryzae; Thielaviopsis diseases, caused for example by Thielaviopsis basicola; ear and panicle diseases such as: Alternaria diseases, caused for example by Alternaria spp. ; Aspergillus diseases, caused for example by Aspergillus flavus or A. niger; Cladosporium diseases, caused for example by Cladosporium erbarum; Claviceps diseases, caused for example by Claviceps purpurea; Fusarium diseases, caused for example by Fusarium culmorum, F. graminearum, F. sporotrichioides, or F. verticil I ioides; Gibberella diseases, caused for example by Gibberella zeae; Macrophomina diseases, caused for example by Macrophomina phaseolina; Monographella diseases, caused for example by Monographella nivalis,' smut and bunt diseases such as: Eballistra diseases, caused for example by Eballistra oryzae; Sporisorium diseases, caused for example by Sporisorium reilianum (Sphacelotheca reiliana): Tilletia diseases, caused for example by Tilletia caries, T. horrida, or T. indica; Urocystis diseases, caused for example by Urocystis occulta or U trilici; Ustilago diseases, caused for example by Ustilago maydis, U nuda, or U. trilici: fruit rot and mold diseases such as: Alternaria diseases, caused for example by Alternaria citri, or A. solani: Anthracnose diseases, caused for example by Aspergillus diseases, caused for example by Aspergillus flavus or A. niger; Botryosphaeria diseases, caused for example by Botryosphaeria obtusa; Botrytis diseases, caused for example by Botrytis cinerea: Cercospora diseases, caused for example by Cercospora coffeicola; Cladisporium diseases, caused for example by Cladosporium cladosporiodes, C. cucumerinum, or C. musae; Colletotrichum diseases, caused for example by Colletotrichum acutatum, C. coccodes, C. fioriniae, C. gloeosporiodes, C. kahawae, or C. obiculare: Fusarium diseases, caused for example by Elsinoe diseases, caused for example by Elsinoe ampelina or E. veneta; Fusarium mangiferae; Guignardia diseases, caused for example by Guignardia bidwellii, G. citricarpa, or G. musae; Monolinia diseases, caused for example by Monolinia fructicola, M. fructigena, M. laxa, orM. vaccinii-corymbosi; Mucor diseases, caused for example by Mucor mucedo; Penicillium diseases, caused for example by Penicillium digitatum, or P. expansum; Phytophthora diseases, caused for example by Phytophthora capsici; Rhizopus diseases caused by example by Rhizopus oryzae, or R. stolonifer; Saccharomyces diseases, caused for example by Saccharomyces cerevisiae;

[0134] Sclerotinia diseases, caused for example by Sclerotinia sclerotiorum; Trichothecium diseases caused for example by Tricothecium roseum; scab diseases, caused for example by Elsinoe fawcettii, Venturia carpophila, Venturia effusa, Venturia inequalis, or Venturia pyrina; seed and soilborne decay, mold, wilt, rot and damping-off diseases: Alternaria diseases, caused for example by Alternaria brassicicola; Aphanomyces diseases, caused for example by Aphanomyces cochlioides, or A. euteiches; Ascochyta diseases, caused for example by Ascochyta lends; Aspergillus diseases, caused for example by Aspergillus flavus, or A. niger; Bretziella diseases, caused for example by B. fagacearum; Ceratocystis diseases, caused for example bye Ceratocystis cacaofunesta or C. fimbriata; Cladosporium diseases, caused for example by Cladosporium herbarum; Cochliobolus diseases, caused for example by Cochliobolus lunata or C. sativus; (Conidiafornr. Drechslera. Bipolar is Syn: Helminlhosporium): Colletotrichum diseases, caused for example by Colletotrichum coccodes; Fusarium diseases, caused for example by Fusarium culmorum, F. subglutinans, or F. virguliforme; Ganoderma diseases, caused for example by Ganoderma orbiforme; Gibberella diseases, caused for example by Gibberella fujikuroi, or G. zeae; Macrophomina diseases, caused for example by Macrophomina phaseolina; Monographella diseases, caused for example by Monographella nivalis; Penicillium diseases, caused for example by Penicillium expansum; Phoma diseases, caused for example by Phoma lingam; Phomopsis diseases, caused for example by Phomopsis sojae; Phytophthora diseases, caused for example by Phytophthora cactorum; Pyrenophora diseases, caused for example by Pyrenophora graminea; Pyricularia diseases, caused for example by Pyricularia oryzae;

[0135] Pythium diseases, caused for example by Pythium aphanidermatum, P. irregular e, or P. ultimum; Rhizoctonia diseases, caused for example by Rhizoctonia solani; Rhizopus diseases, caused for example by Rhizopus oryzae; Sclerotinia diseases, caused for example by Sclerotinia borealis, or S. homoeocarpa; Sclerotium diseases, caused for example by Sclerotium rolfsii; Septoria diseases, caused for example by Septoria nodorum;

[0136] Trichothecium diseases, caused for example by Trichothecium roseum; Typhula diseases, caused for example by Typhula incarnata, or T. ishikariensis; Verticillium diseases, caused for example by Verticillium albo-atrum, V. dahliae, or V. longisporum; canker, broom, dieback, and decline diseases such as: Armillaria diseases, caused for example by Armillaria mellea; Botryosphaeria diseases, caused for example by Botrysphaeria dothidea or B. obtusa; Cryphonectria disease, caused for example by Cryphonectria parasitica; Diaporthe diseases, caused for example by Diaporthe eres; Esca diseases, caused for example by Phaemoniella clamydospora, or Phaeoacremonium aleophilum; Eutypa diseases, caused for example by Eutypa lata; Fusarium diseases, caused for example by Fusarium circinatum (Gibberella circinala) or F. subglutinans; Ganoderma diseases caused for example by Ganoderma boninense; Lasiodiplodia diseases, caused for example by Lasiodiplodia theobromae; Neonectria diseases, caused for example by Nectria ditissima, or N. galligena; Ophiostoma diseases, caused for example by Ophiostoma ulmi; Phomopsis diseases, caused for example by Phomopsis conorum or P. juniper ovor a; Phytophthora diseases, caused for example by Phytophthora cinnamoni, P. cactorum, or P. ramorumRigidoporus diseases caused for example by Rigidoporus lignosus; Septoria diseases, caused for example by Septoria aciculosa; Taphrina diseases, caused for example by Taphrina betulina leaf blister or leaf curl diseases such as: Exobasidium diseases caused for example by Exobasidium vexans; Taphrina diseases, caused for example by Taphrina deformans,' diseases of flowers, blossoms, and seeds such as: Botrytis diseases caused for example by Botrytis cinerea: Cercospora diseases, caused for example by Cercospora kickuchii; Fusarium diseases, caused for example by Fusarium graminearum or F. sporotrichioides;Monolinia diseases, caused for example by Monolinia fructicola, or M. vaccinii-corymbosi; Phomopsis diseases, caused for example by Phomopsis longicolla, or P. sojae; diseases of tubers such as: Alternaria diseases, caused for example by Alternaria solani; Colletotrichum diseases, caused for example by Colletotrichum coccodes; Fusarium diseases, caused for example by Fusarium acuminatum or F. solani; Helminthosporium diseases caused for example by Helminthosporium solani; Phytophthora diseases, caused for example by Phytophthora erythroseptica or P. infestans; Rhizoctonia diseases caused for example by Rhizoctonia solani; Spongospora diseases, caused for example by Spongospora subterranea; Verticillium diseases, caused for example by Verticillium dahliae;

[0137] Club root diseases such as: Plasmodiophora diseases, cause for example by Plamodiophora brassicae; diseases caused by organisms such as: Xanthomonas species for example Xanthomonas campestris pv. oryzae; Pseudomonas species for example Pseudomonas syringae pv. lachrymans; Erwinia species, for example Erwinia amylovora.

[0138] The compositions described herein may also be used against fungal diseases liable to grow on or inside timber. The term “timber” means all types of species of wood, and all types of working of this wood intended for construction, for example solid wood, high- density wood, laminated wood, and plywood.

[0139] Also described herein are methods of treating or preventing a plant disease comprising applying to a plant having a plant disease or at risk of developing a plant disease an effective amount of at least one antifungal agent provided herein wherein the antifungal agent controls a plant pathogen that causes the plant disease.

[0140] The term “treat” or “treating” or its derivatives includes substantially inhibiting, slowing, or reversing the progression of a condition, substantially ameliorating symptoms of a condition or substantially preventing the appearance of symptoms or conditions brought about by the pathogen that causes the plant disease.

[0141] The terms “controlling” and “protecting a plant from a pathogen” refers to one or more of inhibiting or reducing the growth, germination, reproduction, and / or proliferation of a pathogen of interest; and / or killing, removing, destroying, or otherwise diminishing the occurrence, and / or activity of a pathogen of interest. As such, a plant treated with the antifungal composition provided herein may show a reduced disease severity or reduced disease development in the presence of plant pathogens by a statistically significant amount.

[0142] The term “prevent” and its variations means controlling a disease state prior to fungal or bacterial proliferation or infestation. In this instance, the composition is applied before exposure to the pathogens.

[0143] The term “inhibit” and all variations of this term is intended to encompass the restriction or prohibition of fungal or pest growth.

[0144] A plant, plant part, or area of cultivation treated with the antifungal agent provided herein may show a reduced disease severity or reduced disease development in the presence of plant pathogens by a statistically significant amount. A reduced disease severity or reduced disease development can be a reduction of about 30% to about 40%, to about 50%, to about 60%, to about 70%, to about 80%, to about 90%, or to about 100% when compared to non-treated control plants. In other instances, the plant treated with the antifungal agent provided herein may show a reduced disease severity or reduced disease development in the presence of plant pathogen at least about 25%, at least about 40%, at least about 50%, at least about 51%, about 60%, about 70% about 80%, about 90%, about 91%, about 92%, about 93%, about 94%, about 95%, about 96%, about 97%, about 98%, about 99%, or about 100% when compared to non-treated control plants. Methods for assessing plant disease severity are known, and include, measuring percentage of diseased leaf area (Godoy et al. (2006) FitopatoL Bras. 31(1) 63-68 or by measuring uredinia counts.

[0145] By “antipathogenic compositions” is intended that the compositions are capable of suppressing, controlling, preventing and / or killing the invading pathogenic organism. In specific embodiments, an antipathogenic composition reduces the disease symptoms resulting from pathogen challenge by a statistically significant amount, including for example, at least about 20% to about 50%, at least about 30% to about 70%, at least about 40% to about 80%, or at least about 50% to about 90% or greater. Hence, the methods described herein can be utilized to protect plants from disease, particularly those diseases that are caused by plant pathogens.

[0146] Assays that measure antipathogenic activity are commonly known in the art, as are methods to quantitate disease resistance in plants following pathogen infection. See, for example, U.S. Patent No. 5,614,395, herein incorporated by reference. Such techniques include measuring over time, the average lesion diameter, the pathogen biomass, and the overall percentage of decayed plant tissues. For example, a plant either expressing an antipathogenic polypeptide or having an antipathogenic composition applied to its surface shows a decrease in tissue necrosis (i.e., lesion diameter) or a decrease in plant death following pathogen challenge when compared to a control plant that was not exposed to the antipathogenic composition. Alternatively, antipathogenic activity can be measured by a decrease in pathogen biomass. For example, a plant expressing an antipathogenic polypeptide or exposed to an antipathogenic composition is challenged with a pathogen of interest. Over time, tissue samples from the pathogen-inoculated tissues are obtained and RNA is extracted. The percentage of a specific pathogen RNA transcript relative to the level of a plant specific transcript allows the level of pathogen biomass to be determined. See, for example, Thomma c / a / . (1998) Plant Biology 95: 15107-15111, herein incorporated by reference.

[0147] Furthermore, in vitro antipathogenic assays include, for example, the addition of varying concentrations of the antipathogenic composition to paper disks on agar and placing the disks on agar containing a suspension of the pathogen of interest. Following incubation, clear inhibition zones develop around the discs that contain an effective concentration of the antipathogenic polypeptide (Liu et al. (1994) Plant Biology 91 : 1888-1892, herein incorporated by reference). Additionally, microspectrophotometrical analysis can be used to measure the in vitro antipathogenic properties of a composition (Hu et al. (1997) Plant Mol. Biol. 34:949-959 and Cammue et al. (1992) J. Biol. Chem. 267: 2228-2233, both of which are herein incorporated by reference).

[0148] The antifungal agents or compositions described herein are applied in effective amounts. An effective amount is an amount sufficient to control, treat, prevent, or inhibit the pathogen that causes a plant disease, and / or reduce plant disease severity or reduce plant disease development. In other embodiments, the effective amount is an amount sufficient to improve an agronomic trait of interest and / or to promote or increase plant health, growth or yield of a plant susceptible to a disease. The rate of application of the antifungal agents or compositions may vary according to the pathogen being targeted, the crop to be protected, the efficacy of the antifungal agent, the severity of the disease, the climate conditions, and the like.

[0149] Generally, the rate of application of the antifungal agents described herein is from about 0.01 Kg / Ha to 2 Kg / Ha (e.g., 0.05 Kg / Ha, 0.1 Kg / Ha, 0.2 Kg / Ha, 0.5 Kg / Ha, 1.0 Kg / Ha, or 1.5 Kg / Ha). Methods to assay for the effective amount of the compositions described herein include methods for determining a statistically significant increase in the control of the pathogen or pest targeted by the echinocandin-like compound. Methods to assay for such control are known. Moreover, a statistically significant increase in the control of plant health, yield and / or growth that occurs upon application of an effective amount of the composition provided herein when compared to the plant health, yield and / or growth that occurs when no echinocandin-like compound is applied.

[0150] By “applying” is intended contacting a plant, area of cultivation, seed and / or plant part with an effective amount of the antifungal agents. The application of antifungal composition can occur prior to the planting of the crop (for example, to the soil, the seed, or the plant). In one embodiment, the application of the antifungal composition may be a foliar application. The application may be to the plant, to parts of the plant, to the seeds of the plants to be protected, or to the soil or environment in which the plant to be protected is growing or will grow. Application to the plant or plant parts may be before or after harvest. Application to the seeds will be prior to planting of the seeds.

[0151] Methods for increasing plant yield are provided. The “yield” of the plant refers to the quality and / or quantity of biomass produced by the plant. By “biomass” is intended any measured plant product. An increase in biomass production is any improvement in the yield of the measured plant product. An increase in yield can comprise any statistically significant increase including, but not limited to, at least a 1% increase, at least a 3% increase, at least a 5% increase, at least a 10% increase, at least a 20% increase, at least a 30% increase, at least a 50% increase, at least a 70% increase, at least a 100% or a greater increase in yield compared to a plant not exposed to the antifungal agent.

[0152] As used herein, an “area of cultivation” comprises any region in which one desires to grow a plant. Such areas of cultivation include, but are not limited to, a field in which a plant is cultivated (such as a crop field, a sod field, a tree field, a managed forest, a field for culturing fruits and vegetables, etc.), a greenhouse, a growth chamber, etc.

[0153] Further provided is a coated seed which comprises a seed and a coating on the seed, wherein the coating comprises at least one antifungal agent as described herein. The seed coating can be applied to any seed of interest (i.e., for a monocot or a dicot). Various plants of interest are disclosed elsewhere herein.

[0154] In some examples, the echinocandin-like compounds described herein may be used in combination with other agents, such as fungicides, or other crop protection chemicals. The application may be simultaneous, or the applications may be at different times (sequential), so long as the desired effect is achieved.

[0155] Exemplary Embodiments

[0156] Non-limiting embodiments include:

[0157] Embodiment 1. A composition, comprising: at least one antifungal compound having the structure set forth in Formula I and an agriculturally suitable adjuvant,:

[0158] Formula I wherein: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0159] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3;

[0160] W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, CH2Q, N3, NO2, Cl, F, Br, and I; X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM;

[0161] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and OC(O)R;

[0162] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that this includes both R / S isomers as well as mixtures of R / S isomers at Z);

[0163] T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; each Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R, each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n- substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (e.g., a salt of TFA, HC1, etc.).

[0164] Q, may also be taken together with the adjacent hydroxyl, to form a 6-8-membered heterocycle.

[0165] Embodiment 2. The composition according to embodiment 1, further comprising of one or more additional fungicidal compounds.

[0166] Embodiment 3. A composition, comprising: at least one antifungal compound having the structure set forth in Formula II and an agriculturally suitable adjuvant:

[0167]

[0168] Formula II wherein: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0169] V is selected from the group consisting of H, methyl, and hydroxyl; T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl,

[0170] C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and C(O)OR; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl.

[0171] Embodiment 4. The composition according to embodiment 3, wherein T is selected from the group consisting of C(O)Me, C(O)OMe, CH2CH2NH2, CH2CO2Me.

[0172] Embodiment 5. The composition according to embodiment 3, further comprising of one or more additional fungicidal compounds. Embodiment 6. A composition, comprising: at least one antifungal compound having the structure set forth in Formula III and an agriculturally suitable adjuvant:

[0173] Formula III wherein: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0174] V is selected from the group consisting of H, methyl, and hydroxyl; X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl.

[0175] Embodiment 7. The composition according to embodiment 6, wherein X is selected from a group consisting of I, SO3H, NHC(O)CH2CH2COOH and C=CH.

[0176] Embodiment 8. The composition according to embodiment 6, further comprising one or more additional fungicidal compounds.

[0177] Embodiment 9. A composition comprising: at least one antifungal compound having the structure set forth in Formula IV and an agriculturally suitable adjuvant:

[0178]

[0179] Formula IV wherein: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0180] V is selected from the group consisting of H, methyl, and hydroxyl; Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH,

[0181] OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and (N)OR; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”and N(+)RR’R”; each of R’, R’, and R’” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl.

[0182] Embodiment 10. The composition according to embodiment 9, further comprising one or more additional fungicidal compounds.

[0183] Embodiment 11. A composition, comprising: at least one antifungal compound having the structure set forth in Formula V and an agriculturally suitable adjuvant:

[0184] Formula V wherein: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl and heteroaryl;

[0185] V is selected from the group consisting of H, methyl, and hydroxyl;

[0186] W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM CH2Q, and CN; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;

[0187] Q is selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, and I; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl.

[0188] Embodiment 12. The composition according to embodiment 11, wherein W is selected from a group consisting of C(0)NH2, C(O)OCH2CH3, CH2NH2, cyano and CH20H

[0189] Embodiment 13. The composition according to embodiment 11, further comprising one or more additional fungicidal compounds.

[0190] Embodiment 14. A composition, comprising: at least one antifungal compound having the structure set forth in Formula VI and an agriculturally suitable adjuvant:

[0191]

[0192] Formula VI wherein: U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;

[0193] V is selected from the group consisting of H, methyl, and hydroxyl;

[0194] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0195] Q is selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n-substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)n0H, (CH2)nCO2R, and salts thereof (TFA, HC1, etc.).

[0196] Also Q, may be taken together with the adjacent hydroxyl, may also form a 6-8- membered heterocycle.

[0197] Embodiment 15. The composition according to embodiment 14, further comprising of one or more additional fungicidal compounds.

[0198] Embodiment 16. The composition according to any of embodiments 1-15, wherein the hemi- aminal functional group of the at least one antifungal compound is replaced by an amide, a hemiaminal ether, a thioaminal, or an aminal, wherein the composition gains greater aqueous stability and has greater whole plant activity relative to pneumocandin.

[0199] Embodiment 17. A method for controlling or treating a disease in a plant, comprising: applying to the plant at least one antifungal compound, wherein the at least one antifungal compound is selected from a lipophilic cyclic hexapeptidal candin / fungin derivative (echinocandin) having the structure set forth in one of Formulas I- VI.

[0200] Embodiment 18. A composition comprising at least one antifungal compound having the structure set forth in Formula VII and an agriculturally suitable adjuvant:

[0201] Formula VII wherein: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0202] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3;

[0203] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;

[0204] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0205] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ and NS(O2)R. Also Q, may be taken together with the adjacent hydroxyl, may also form a 6-8-membered heterocycle.

[0206] Embodiment 19. The composition according to embodiment 18, further comprising one or more additional fungicidal compounds.

[0207] Embodiment 20. A composition comprising at least one antifungal compound having the structure set forth in Formula VIII and an agriculturally suitable adjuvant:

[0208]

[0209] Formula VIII wherein: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0210] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3;

[0211] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R;

[0212] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0213] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n-substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (TFA, HC1, etc.). Also, Q may be taken together with the adjacent hydroxyl, may also form a 6-8-membered heterocycle. Embodiment 21. The composition according to Embodiment 20, further comprising one or more additional fungicidal compounds.

[0214] Embodiment 22. A composition comprising at least one antifungal compound having the structure set forth in Formula IX and an agriculturally suitable adjuvant:

[0215]

[0216] Formula IX wherein: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0217] V is selected from the group consisting of H, methyl, and hydroxyl;

[0218] A is N or O; n = 0-3;

[0219] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R;

[0220] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0221] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n-substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (TFA, HC1, etc.).

[0222] Also, Q may be taken together with the adjacent hydroxyl, may also form a 6-8- membered heterocycle.

[0223] Embodiment 23. The composition according to embodiment 22, further comprising of one or more additional fungicidal compounds. Embodiment 24. A composition comprising at least one antifungal compound having the structure set forth in Formula X and an agriculturally suitable adjuvant: where: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0224] V is selected from the group consisting of H, methyl, and hydroxyl;

[0225] A is N or O; n = 0-3;

[0226] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R;

[0227] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of the R / S isomers at Z);

[0228] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)nAryl, (CH2)n-substituted Aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (TF A, HC1, etc ).

[0229] Also, Q may be taken together with the adjacent hydroxyl, may also form a 6-8- membered heterocycle. Embodiment 25. The composition according to embodiment 24, further comprising one or more additional fungicidal compounds.

[0230] Embodiment 26. A composition comprising at least one antifungal compound having the structure set forth in Formula XI and an agriculturally suitable adjuvant: where: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0231] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3; Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH,

[0232] OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and (N)0R; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”and N(+)RR’R”; and each of R’, R’, and R’” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl.

[0233] Embodiment 27. The composition according to embodiment 26, further comprising one or more additional fungicidal compounds. Embodiment 28. A composition comprising at least one antifungal compound having the structure set forth in Formula XII and an agriculturally suitable adjuvant: where: U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;

[0234] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3;

[0235] W = C=O or CH2;

[0236] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;

[0237] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0238] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n-substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (TFA, HC1, etc.).

[0239] Also, Q may be taken together with the adjacent hydroxyl, may also form a 6-8- membered heterocycle.

[0240] Embodiment 29 The composition according to embodiment 28, further comprising one or more additional fungicidal compounds. Embodiment 30. A composition comprising at least one antifungal compound having the structure set forth in Formula XIII and an agriculturally suitable adjuvant: where: U is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, C(O)alkyl, , C(O)aryl, C(O)heteroalkyl, and C(O)heteroaryl or a group consisting of:

[0241] K is either H or -OH

[0242] V is selected from the group consisting of H, methyl, and hydroxyl; n = 0-3 L is either -OH, -B(OH)2, -B(OR)2 or selected from a group consisting of: where R is independently alkyl and joined as ring or alky-substituted ring and n=0-3 A is either O or NH W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(O)

[0243] Cl, F, Br, I or a group consisting o

[0244] X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM;

[0245] Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and OC(O)R;

[0246] Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q (it is understood that both R / S isomers are included as well as mixtures of R / S isomers at Z);

[0247] M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;

[0248] Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R;

[0249] Q, taken together with K, may also form a 6-8-membered heterocycle; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl, and (CH2)nC(O)NRR’), (CH2)n(N(+)RR’R”), substitute aryl, (CH2)naryl, (CH2)n-substituted aryl, (CH2)nNRR’, (CH2)n-heteroaryl, (CH2)nOH, (CH2)nCO2R, and salts thereof (TFA, HC1, etc.).

[0250] Embodiment 31. The composition according to embodiment 30, further comprising one or more additional fungicidal compounds.

[0251] Embodiment 32. The composition according to any of embodiments 18-31, wherein the hemi-aminal functional group of the at least one antifungal compound is replaced by an amide, a hemiaminal ether, a thioaminal, or an aminal, wherein the composition gains greater aqueous stability and has greater whole plant activity relative to pneumocandin. Embodiment 33. A method for controlling or treating a disease in a plant, comprising: applying to the plant at least one antifungal compound, wherein the at least one antifungal compound is selected from a lipophilic cyclic hexapeptidal candin / fungin derivative (echinocandin) having the structure set forth in one of Formulas VII-XIII. Embodiment 34. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 55.

[0252] Example 55

[0253] Embodiment 35. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 48B.

[0254] Embodiment 36. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 48A.

[0255]

[0256] Embodiment 37. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 82. Embodiment 38. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 81.

[0257]

[0258] Embodiment 39. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 84.

[0259] Embodiment 40. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 18.

[0260]

[0261] Embodiment 41. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 134. Example 134

[0262] Embodiment 42. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 158.

[0263]

[0264] Embodiment 43. A method for controlling or treating a disease in a plant, comprising: applying to the plant the antifungal natural product Pneumocandin bO. Pneumocandin bO Embodiment 44. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described as Compound S-040. Compound S-040 Embodiment 45. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described as Compound 9A. Compound 9A

[0265] Embodiment 46. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 56.

[0266] Embodiment 47. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described as Compound 9.

[0267]

[0268] Embodiment 48. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 43. Example 43 Embodiment 49. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 129.

[0269] Example 129

[0270] Embodiment 50. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound as described in Example 166. Example 166

[0271] The following examples are offered by way of illustration and not by way of limitation.

[0272] EXAMPLES

[0273] Example 1:

[0274] On plate efficacy data were obtained for various control and echinocandin-like compounds. Each test compound was assessed at four concentrations (20, 2, 0.2, and 0.02 ppm). A stock solution in a DMSO / water mix was produced for each dose, i.e., 200, 20, 2 and 0.2 ppm, and 10 pl of this was added to the appropriate wells of a 96 well plate on agar. To each well, 90 pl of an appropriate agar spore suspension was added to give the final well concentrations outlined above. The species tested were Botrytis cinerea. Alternaria allernala. Zymoseptoria tritici , Phytophthora caclorum. Fusarium graminearum, and Magnaporthe grisea (e.g., Magnaporthe oryzae). Plates were incubated at 18 °C for 2 to 5 days and assessed for growth relative to a control with no test compound.

[0275] The value shown in Table 1 was the lowest dose at which control was 50% or greater, compared to a control with no test compound. If the compound does not show 50% control at 20 ppm, the value is shown at “>20” and a value of 0.02 ppm is the lowest dose tested.

[0276] As seen in Table 1, Pneumocandin Boand Micafungin, two members of the echinocandin family, have superior activity to the agrochemical commercial standards Mancozeb, Azoxystrobin, Iprodione, and Propiconazole especially on Z. Tritici.

[0277] Table 1. Lowest dose of compound at which the organism control was 50% or greater

[0278] Example 2:

[0279] On plate efficacy data on agar were obtained as in Example 1 for a variety of compounds that have been reported to have in planta fungicidal activity against an agricultural set of pathogens that are not of concern for human health. As can be seen in Table 2, in contrast to the results seen with echinocandin-like compounds, the human pathogen targeting fungicides tested below were largely not active against agriculturally relevant fungi Botrytis, Fusarium, Allernaria, Magnaporthe, Phytophora and Septoria. Table 2. Lowest dose of compound at which the organism control was 50% or greater

[0280] Example 3

[0281] On plate efficacy data on agar were obtained as in Example 1 for a variety of compounds of the structure of Formula II. As can be seen in Table 3, the compounds according to Formula II are equally or more potent than the natural echinocandin product, pneumocandin BO, against agriculturally relevant fungi Botrytis, Fusarium, Alternaria, Magnaporthe, Phytophora and Septoria. Table 3. Lowest dose of compound at which the organism control was 50% or greater (compared to a control with no test compound)

[0282] Example 4

[0283] On plate efficacy data on agar were obtained as in Example 1 for a variety of compounds of the structure of Formula III. As can be seen in Table 4, these analogs are equally or more potent than the natural echinocandin product, pneumocandin BO, against agriculturally relevant fungi Botrytis, Fusarium, Allernaria, Magnaporthe, Phytophora and Septoria.

[0284] Formula III

[0285] Table 4. Lowest dose of compound at which the organism control was 50% or greater (compared to a control with no test compound) Example 5

[0286] On plate efficacy data on agar were obtained as in Example 1 for two compounds of the structure of Formula IV. As can be seen in Table 5, these analogs are equally or more potent than the natural echinocandin product, pneumocandin BO, against agriculturally relevant fungi Botrytis, Fusarium, Alternaria, Magnaporthe, Phytophora and Septoria.

[0287]

[0288] Table 5. Lowest dose of compound at which the organism control was 50% or greater

[0289] (compared to a control with no test compound) Example 6

[0290] On plate efficacy data on agar were obtained as in Example 1 for a variety of compounds of the structure of Formula V. As can be seen in Table 6, several of these analogs were equally or more potent than the natural echinocandin product, pneumocandin BO, against agriculturally relevant fungi Botrytis, Fusarium, Allernaria, Magnaporthe, Phytophora and Septoria.

[0291] Formula V Table 6. Lowest dose of compound at which the organism control was 50% or greater (compared to a control with no test compound)

[0292] Example 7

[0293] On plate efficacy data on agar were obtained as in Example 1 for a variety of compounds of the structure of Formula VI. As can be seen in Table 7, several of these analogs were equally or more potent than the natural echinocandin product, pneumocandin BO, against agriculturally relevant fungi Botrytis, Fusarium, Allernaria, Magnaporthe, Phytophora and Septoria.

[0294] Table 7. Lowest dose of compound at which the organism control was 50% or greater

[0295] (compared to a control with no test compound)

[0296] Example 8

[0297] Compounds (as described below, based on Formulas VII-XIII) were screened for activity against Magnaporthe oryzae (M oryzae) and Zymoseptoria tritici (Z. tritici) with a plate based assay. Unless specified, fungal organisms used in these assays were maintained on potato dextrose agar (PDA) or V8 agar and spores were isolated from the cultures after 1-2 weeks of incubation at room temperature (20-22°C) with 12 hours fluorescent light (Philips, F40LW). The final concentrations of all inocula used in in vitro antifungal assays were 1 x 105CFU / mL. Magnaporthe oryzae'. maintained on oatmeal agar (30g oatmeal powder, 15g agar, lOOOmL distilled water). Cultures were incubated at 25°C under continuous fluorescent light. After 14 days, spores are collected and brought to the test concentration.

[0298] Zymoseptoria tritici'. maintained on YSA agar (10g yeast extract 10g, 10g surcrose, 15g agar, lOOOmL distilled water). Plates incubated at room temperature (20-22°C) with 12 hours fluorescent light for 3-5 days. Spores were transferred to YSB and incubated for 3-5 days. The YSB was filtered through one layer of miracloth and diluted in half strength YSB.

[0299] Compounds were stocked in DMSO with the concentration of 5000 pg / mL (stored at - 20°C). The stock solutions were further diluted into sterile, half strength broth media in the in vitro assay, in which DMSO final concentration is not greater than 1% (v / v). The half maximal effective concentration (EC50) for individual compounds was determined by following a modified broth microdilution protocol. The studies were performed in clear, flat bottom, 96-well microtiter plates. The individual EC50 were determined in triplicate in a final volume of 0.2 mL / well with antifungal concentrations of 0.05 - 25 pg / mL (10 serial dilutions down from 25 pg / mL [25, 12.5, 6.25, 3.13, 1.56, 0.78, 0.39, 0.20, 0.10, and 0.05 pg / mL]; control studies with 0 pg / mL of compounds were performed in parallel for each plate). The final concentrations of all inocula used in in vitro antifungal assays were 1 x 105CFU / mL.

[0300] Plates sealed with clear polyester film were incubated at 22°C. The progress of fungal growth was measured at 72 hours. The EC50 values were determined as the lowest antifungal concentrations that inhibited fungal growth by greater than 50% (determined as relative absorbance using the Bio-Tek® Synergy™ Hl microplate reader at 600 nm) relative to the corresponding antifungal -free control. When compounds were screened in vitro more than once, the average EC50 of all trials is reported.

[0301] In the table below, “++” indicates an EC50 of 1 ppm or less, “+” indicates an EC50 of between 1 ppm and 25 ppm, and indicates an EC50 of 25 ppm or greater.

[0302] Table 8. Qualitative activity level for EC50 vs M. oryzae and Z. tritici in vitro for selected examples

[0303] M. oryzae Z. tritici

[0304] Example # Structure EC50 EC50

[0305] (ppm) (ppm)

[0306]

[0307] <T> <T> <T> tn 2

[0308]

[0309]

[0310]

[0311]

[0312]

[0313]

[0314]

[0315]

[0316]

[0317]

[0318]

[0319]

[0320]

[0321] -Ill-

[0322] Example 9

[0323] On Planta Studies Systemicity

[0324] Systemicity is the phenomenon wherein a compound can travel in the plant’s vascular either by the xylem or phloem. With fungicides it is desirable to have movement from the site of application of the fungicide to the tip of the leaf. Because the xylem is generally pH 5- 6, it has an affinity for basic molecules. Thus for the compounds to be systemically active, their water solubility is expected to be > 10 mg / L and LogD < 3 at pH 7. We have found that the echinocandin-like molecules described herein have fair (5-15% movement in the leaf) to excellent (100% movement in the leaf) systemicity as measured by painting a line across the middle of the leaf with the compound, infecting it and measuring in millimeters how far to the end of the leaf is clean of infection. This is indicative of the distance travelled by the compound in the leaf tissue, i.e. its systemicity. Thus, the compounds described herein can protect the plant for more than where the compound was applied. There are degrees of systemicity depending on the compound as indicated above. Pneumocandin does not have acidic or basic functional groups and has a solubility of 2.4 mg / L as well as a LogD of 3.4 at pH 7. Therefore, without being limited by theory, it is believed to be systemically inactive. This was demonstrated in the experiments above as it did not travel in the leaf tissue (0 mm). Translaminar activity

[0325] There also is a characteristic of certain molecules to exhibit “translaminar” activity. This means that a compound can travel through the leaf and protect the underside of the leaf. Some of the compounds disclosed here are translaminar. Pneumocandin itself does not demonstrate any translaminar activity.

[0326] Fungicidal Activity in Planta

[0327] Table 9 A below shows the translation of Septoria control from in vitro 96 well plates on agar to in Planta activity at 25 ppm. As can be seen below, all of the compounds including pneumocandin exhibit excellent in vitro activity with a BP50of 0.02 ppm. However, pneumocandin did not translate its activity to Septoria on wheat plants well at all at 25 ppm, whereas excellent control can be seen with the new analogs. Compounds with multiple substitutions, wherein more than one of the substituents T, W, X, Y and Z are different than that of pneumocandin, were found to be highly active in in vitro and in planta assays.

[0328] Table 9A: Fungicidal activity of echinocandin-like compounds

[0329] Further Greenhouse testing

[0330] For greenhouse studies, the compounds were prepared in the following manner: Compounds were dissolved in acetone or ethanol for a concentration of 1 mg / mL. All % are (v / v) based on the final volume of the spray solution. The aqueous phase was prepared by mixing 49.95% deionized water and 0.05% Silwet L-77 to a homogenous solution. The acetone phase was then prepared by aliquoting 4-50% of compound stock into a vessel and then adding 0-46% to bring the acetone or ethanol phase to 50% of the total solution. The acetone or ethanol phase was then mixed with the aqueous phase and was then ready for application.

[0331] Greenhouse efficacy against Zymoseptoria tritici on wheat (Triticum aestivuni) - Wheat Septoria Leaf Blotch (SLB) Assay

[0332] When seeds were sown into three-inch pots containing sterile potting mix. Plants were grown for 14 days prior to application of treatments. Spray solutions were made using the method described above and diluted to 250, 100, and 20 mg / L and lower for potent compounds. An untreated check and industry standard positive check are included in each assay. For each treatment, the solution is applied to nine wheat plants until runoff, then allowed to dry for 24 hours prior to inoculation.

[0333] Post application and prior to inoculation, pots were arranged in assay chambers in a completely randomized design. Zymoseptoria tritici was prepared on YSA using methods described above and the assay was inoculated at a spore concentration 1 x 106cfu / mL, soaking each plant to run off with the spore suspension.

[0334] Seventeen days after inoculation, when the untreated plants have reached 60-70% wheat SLB infection, disease ratings were recorded by giving each plant a percentage infection score. All data is reported as percent disease control compared to the untreated check plants. Statistical analysis and separation of means were calculated using one-way ANOVA(a=0.05).

[0335] Table 9B. On Planta activity of selected Examples on Wheat reported as percent inhibition of fungus growth at a dose of lOOppm.

[0336] Example 10 (Compound 1): To a solution of pneumocandin bO (100 mg, 0.093 mmol) in dimethylformamide

[0337] (DMF) (1.2 mL) was added Cyanuric chloride (40 mg, 0.216 mmol) at 10° C. After stirring for about 10 minutes, the reaction mixture was quenched with aqueous sodium acetate (NaOAc) (2N, 5 mL). The mixture was concentrated in vacuo and the residue was suspended in H2O (20 mL). The mixture was filtered and the solid was collected and purified by Prep- HPLC to afford Compound 1 (19.5 mg, 20% yield) as a white solid. PartialJH NMR: (CD3OD, 400 MHz): <5’7.12 (d, J = 8.0 Hz, 2H), 6.74 (d, J = 8.4 Hz, 2H), 5.29 (d, J = 1.2, 1H), 5.02-4.98 (m, 2H), 3.78 (m, 2H), 2.80 (m, 1H), 2.74 (m, 1H), 2.43 (m, 1H), 2.29-2.22 (m, 4H); LC-MS: m / z 1046.8[M+H]+. Example 11 (Compound 2): To a solution of Compound 1 (89 mg, 0.084 mmol) in methanol (MeOH) (2 mL) was added CoCl2.6H2O (137.5 mg, 0.577 mmol) followed by NaBH4(109 mg, 2.88 mmol) portion-wise over a period of 10 min at room temperature. The resulting mixture was stirred for 30 min at room temperature, after which aqueous HC1 (2N, 29 mL) was added to quench the reaction. After stirring for a further 30 minutes, the mixture was filtered. The solid was washed with H2O (5 mL) and dried in vacuo to give the crude product which was further purified by Prep-HPLC to afford Compound 2 (5.5 mg, 6.2%) as a brown solid. PartialJH NMR (CD3OD, 400 MHz): <77.03 (d, J = 8.8 Hz, 2H), 6.69 (d, J = 8.4 Hz, 2H), 5.13 (d, J = 2.4 Hz, 1H), 3.93 (m, 3H), 3.71 (m, 3H), 2.89 (m, 2H), 2.35 (m, 1H), ; LC-MS: m / z 1050.8[M+H]+. To a solution of pneumocandin bO (100 mg, 0.094 mmol) in DMF (2 mL) were added 2-(diethylamino)ethanethiol (48 mg, 0.28 mmol) and phenylboronic acid (27 mg, 0.19 mmol). The mixture was cooled to 0° C and trifluoroacetic acid (TFA) (32 mg, 0.28 mmol) was added at 0°C. Then the mixture was warmed to 25° C and stirred for overnight. Then the mixture was purified by prep-HPLC to afford Compound 3 (8 mg, 7.27% yield) as a white solid. Partial Tf NMR (MeOH-t / 4, 400 MHz): <77.03 (d, J= 8.4 Hz, 2H), 6.65 (d, J= 8.8 Hz, 2H), 5.20 (d, J= 2.0 Hz, 1H), 5.00 (d, J= 4.0 Hz, 1H), 4.89 (d, J= 3.2 Hz, 1H), 4.49-4.40 (m, 4H), 4.30-4.25 (m, 2H), 4.20-4.18 (m, 3H), 4.12-4.11 (m, 1H), 3.99-3.96 (m, 1H), 3.90- 3.85 (m, 2H), 3.70-3.67 (m, 2H), 2.72-2.50 (m, 9H), 2.40-2.30 (m, 2H), 2.14-1.84 (m, 7H), 1.53-1.49 (m, 2H), 1.35-1.16 (m, 16H), 1.05 (d, J= 6.4 Hz, 3H), 0.97 (t, J= 7.2 Hz, 7H), 0.85-0.83 (m, 1H), 0.82-0.77 (m, 1H), 0.76-0.75 (m, 8H). LCMS: m / z 1180.5 [M-H20+H]+.

[0338] Example 13 (Compound 4):

[0339] To a solution of Compound 2 (50 mg, 0.049 mmol) and Pd(OH)2 / C (20 mg) in MeOH (5 mL), 37% formaldehyde (2 mL) was added. The mixture was stirred under H2balloom overnight at room temperature. The solid was filtered out and the filtrate was concentrated under reduced pressure to give a residue which was purified by Prep-HPLC to give Compound 4 (7.7 mg, 34.7% yield) as a white solid. Partial 'HNMR (CD3OD,400 MHz), 3 6.91 (d, J = 8.0 Hz, 2H), 6.62 (d, J = 8.4 Hz, 2H), 4.53-4.46 (m, 11H), 4.41 (m, 1H), 4.30-4.20 (m, 3H), 4.10 (m, 1H), 3.95-3.92 (m, 3H), 3.73-3.70 (m, 3H), 2.58 (s, 6H); LC-MS: m / z 1047.5[M+H]+. Example 14 (Compound 5):

[0340] To a suspension of Compound 4 (10 mg, 0.0095 mmol) in acetonitrile (MeCN, ACN) (3 ml), iodomethane (Mel) (2 mg, 0.014 mmol) was added. The mixture was stirred overnight at room temperature. The mixture was concentrated and the residue was purified by Prep-HPLC to give Compound 5 (3.6 mg, 36% yield) as a white solid. PartialJH NMR (MeOD-d4,400 MHz), 3 6.91 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 8.8 Hz, 2H), 4.90 (d, J = 2.8 Hz, 1H), 4.50 (m, 4H), 4.41 (d, J = 1.6 Hz, 1H), 4.29-4.20 (m, 4H), 4.08 (d, J = 5.6 Hz, 1H), 3.94-3.87 (m, 3H), 3.75-3.69 (m, 3H), 3.64-3.60 (m, 1H), 3.55-3.47 (m, 1H), 3.41-3.34 (m, 1H), 3.04 (s, 9H), 2.88 (dd, J = 14.4 Hz, 3.6 Hz, 1H), 2.60-2.55 (m, 1H), 2.50-2.45 (m, 1H),

[0341] 2.41-2.36 (m, 1H), 2.31 (d, J = 11.6 Hz, 1H), 2.23-2.08 (m, 5H), 2.02-1.87 (m, 4H), 1.83- 1.74 (m, 2H), 1.50 (m, 3H), 1.35-1.07 (m, 23H), 1.03-0.94 (m, 3H), 0.85-0.74 (m, 11H); LC- MS: m / z 1061.5[M]+.

[0342] Example 15 (Compound 6):

[0343] A mixture of Caspofungin Diacetate (100 mg, 0.091 mmol), Formaldehyde (37% H2O solution, 4 mL) and 10% Pd / C (20 mg) in methanol was stirred overnight under H2balloon. The mixture was filtrated and the filtrate was concentrated under reduced pressure. The residue was purified by Prep-HPLC to give Compound 6 (17 mg, 16.3% yield) as a white solid. Partial 'H NMR (CD3OD, 400 MHz): 57.16 (d, J= 7.2 Hz, 2H), 6.81 (d, J= 8.8 Hz, 2H), 4.18 (m, 1H), 4.08-4.04 (m, 3H), 2.38 (s, 6H), 2.28 (s, 6H); LC-MS: m / z 1149.7[M+H]+.

[0344] Example 16 (Compound 7):

[0345] To a suspension of Compound 6 (15 mg, 0.013 mmol) and NaHCO3(4.4 mg, 0.052 mmol) in MeCN (3 mL), Mel (3.7 mg, 0.026 mmol) was added. The mixture was stirred overnight at room temperature and concentrated. The residue was purified by Prep-HPLC to give Compound 7 (8.6 mg, 46.2% yield) as a white solid. Partial ’H NMR: (CD3OD, 400 MHz), <5 6.97 (d, J = 8.4 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 4.90 (d, J = 2.8 Hz, 1H), 4.81 (d, J = 6.0 Hz, 1H), 4.62 (d, J = 1.6 Hz, 1H), 4.49-4.35 (m, 4H), 4.23-4.18 (m, 3H), 4.14-4.12 (m, 1H), 4.04 (d, J = 5.6 Hz, 1H), 3.90-3.86 (m, 3H), 3.77-3.68 (m, 3H), 3.46-3.30 (m, 4H), 3.07, 3.06 (s, 18H), 2.90-2.87 (m, 1H), 2.37-2.32 (m, 1H), 2.21-1.75 (m, 10H), 1.54-1.48 (m, 2H), 1.38-1.07 (m, 19H), 1.03-0.95 (m, 2H), 0.85-0.75 (m, 11H); LC-MS: m / z 1292.3 [M+114]+.

[0346] Example 17 (Compound 8):

[0347] To a solution of Compound 2 (50 mg, 0.049 mmol) and Pd(OH)2 / C (20 mg) MeOH (5 mL), Acetaldehyde (0.3 mL) was added. The mixture was stirred under H2balloom overnight at room temperature. The solid was filtered out and the filtrate was concentrated under reduced pressure to give a residue which was purified by Prep-HPLC to give Compound 8 (29 mg, 55.7% yield) as a white solid. Partial 'H NMR (CD3OD, 400 MHz), d 6.91 (d, J = 8.8 Hz, 2H), 6.61 (d, J = 8.4 Hz, 2H), 4.88 (d, J = 3.2 Hz, 1H), 4.63-4.42 (m, 7H), 4.30-4.18 (m, 3H), 4.10 (d, J = 4.4 Hz, 1H), 3.95-3.92 (m, 3H), 3.73-3.63 (m, 4H), 3.05- 2.95 (m, 5H), 2.88 (dd, J = 14.0 Hz, 3.6 Hz, 1H), 2.59-2.52 (m, 1H), 2.50-2.44 (m, 1H), 2.40- 2.35 (m, 1H), 2.22-2.07 (m, 4H), 2.01-1.82 (m, 3H), 1.65-1.60 (m, 1H), 1.50 (m, 2H),1.39- 1.07 (m, 26H), 1.05-0.92 (m, 3H), 0.85-0.74 (m, 11H); LC-MS: m / z 1075.5[M+H]+. Example 18 (Compound 9, Compound 9 A, Compound 10):

[0348] To a solution of pneumocandin bO (500 mg, 0.469 mmol) and ethanolamine hydrochloride (915 mg, 9.38 mmol) dimethyl sulfoxide (DMSO) (5 mL), p-Toluenesulfonic acid (20 mg) was added. The reaction mixture was stirred overnight at 30° C. The mixture was diluted with MeCN (30 mL) and filtered. The white solid was collected and washed with saturated NaHCO3(30 mL) and water (5 mL). The cake was collected and dired in vacuo to give the crude product (575 mg) as a white solid. 22.4mg of pure Compound 9 was obtained by Prep-HPLC from 90 mg crude product. PartialJH NMR (CD3OD, 400M Hz), d 8.57 (d, J =8.4 Hz, 1H ), 7.40 (d, J =8.4 Hz, 1H), 7.03 (d, J =8.4 Hz, 2H ), 6.66 (d, J = 8.4 Hz, 2H),5.16 (s, 1H), 5.01-4.98 (m, 1H), 4.90 (m, 1H), 4.47-4.37 (m, 4H), 4.25-4.18 (m, 6H), 4.02-3.99 (m, 1H), 3.88-3.86 (m, 2H), 3.71-3.60 (m, 4H), 3.03 ( s, 3H), 2.66 (dd, J = 3.2 Hz, 15.2 Hz, 1H), 2.39-2.31 (m, 2H), 2.19-2.11 (m, 3H); LC-MS: m / z 1108.5 [M+H]+. This also gave Compound 9A (the N-linked analog) , which could be isolated during Prep-HPLC. 'H NMR (MeOD 400 MHz), 5 ppm 0.86 (br d, .7=6,4 Hz, 8 H) 0.89 (br s, 1 H) 0.91 - 0.96 (m, 1 H) 1.09 (td, .7=13.2, 6.4 Hz, 2 H) 1.20 - 1.36 (m, 15 H) 1.38 - 1.52 (m, 3 H) 1.59 (br s, 2 H) 1.81 - 1.93 (m, 1 H) 1.95 - 2.15 (m, 3 H) 2.22 (br t, J=7.2 Hz, 3 H) 2.39 - 2.59 (m, 3 H) 2.70 - 2.87 (m, 2 H) 3.39 - 3.46 (m, 1 H) 3.51 - 3.61 (m, 1 H) 3.77 - 4.00 (m, 5 H) 4.11 (br s, 1 H) 4.36 (s, 3 H) 4.42 (br d, J=4.8 Hz, 1 H) 4.50 - 4.60 (m, 3 H) 4.62 - 4.71 (m, 2 H) 4.77 (br s, 1 H) 4.95 (br d, J=3.6 Hz, 1 H) 5.14 (br s, 1 H) 6.76 (br d, J=8.0 Hz, 2 H) 7.15 (br d, J=8.0 Hz, 2 H)

[0349] To a mixture of Compound 9 (50 mg, 0.045 mmol) and Pd(OH)2 / C (20 mg) in MeOH (5 mL) was added acetone (2 mL). And the mixture was stirred overnight at room temperature under H2balloon condition. The solid was filtered out and the filtrate was concentrated under reduced pressure to give a residue which was purified by Prep-HPLC to give Compound 10 (16.8 mg, 32.9% yield) as a white solid. Partial 'H NMR (CD3OD, 400 MHz), 3 8.56 (d, J =8.4 Hz, 1H), 7.41 (d, J =8.8 Hz, 2H ), 7.04 (d, J =8.4 Hz, 2H ), 6.67 (d, J = 8.8 Hz, 2H), 5.17 (d, J= 2.0 Hz,lH), 5.00 (dd, J =8.4 Hz, 4.4 Hz,lH), 4.90 (dd, J =8.4 Hz, 3.2 Hz,lH), 4.48-4.44 (m, 3H), 4.40-4.36 (m,lH), 4.28-4.17 (m, 6H), 4.04-4.00 (m, 1H), 3.90-3.83 (m, 2H), 3.75-3.62 (m, 4H), 3.30 (m, 1H), 3.13-3.10 (m, 2H), 2.95 (dd, J =14.4 Hz, 3.2 Hz, 1H), 2.39-2.32 (m, 2H), 2.20-2.12 (m, 3H), 0.77 (d, J= 6.8 Hz, 6H); LC-MS: m / z 1150.5 [M+H]+.

[0350] Example 19 (Compound S- 190V):

[0351] To a solution of pneumocandin bO (1.00 g, 939 pmol, 1.00 eq) in DMSO (10 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (218 mg, 939 pmol, 1.00 eq) and 4-pyridylmethanol (3.07 g, 28.2 mmol, 30.0 eq) at 15°C. The crude solution was purified by prep-HPLC (TFA condition; column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H20(0.1%TFA)-ACN];gradient:30%-55% B over 8.0 min) to give Compound S-190V (0.124 g, 105 pmol, 11.1% yield, 97.8% purity) as a white solid. MS (M+H): 1156 ’H NMR: DMSO 400 MHz: 5 = ppm 8.68 (d, J = 8.0 Hz, 2 H), 8.38 (br d, J = 8.4 Hz, 1 H), 8.31 - 8.25 (m, 2 H), 7.68 (br d, J = 5.6 Hz, 2 H), 7.39 (br d, J = 8.8 Hz, 1 H), 7.23 - 7.11 (m, 4 H), 7.01 (d, J = 8.4 Hz, 2 H), 6.70 - 6.66 (m, 3 H), 6.60 (br s, 1 H), 5.09 (br d, J = 10.4 Hz, 2 H), 4.90 - 4.87 (m, 3 H), 4.80 - 4.78 (m, 2 H), 4.72 (br d, J = 3.6 Hz, 1 H), 4.69 (s, 1 H), 4.65 - 4.61 (m, 2 H), 4.41 - 4.35 (m, 3 H), 4.30 - 4.27 (m, 2 H), 4.21 (br d, J = 2.4 Hz, 2 H), 4.15 - 4.07 (m, 5 H), 4.03 - 3.92 (m, 5 H), 3.77 - 3.69 (m, 4 H), 3.58 - 3.35 (m, 2 H), 2.23 - 2.15 (m, 3 H), 2.06 - 1.99 (m, 4 H), 1.84 - 1.81 (m, 4 H), 1.44 - 1.36 (m, 5 H), 1.21 - 1.17 (m, 17 H), 1.08 - 0.98 (m, 6 H), 0.89 - 0.79 (m, 15 H).

[0352] To a mixture of pneumocandin bO (200 mg, 188 pmol, 1.00 eq) and 2- pyridylmethanol (2.05 g, 18.8 mmol, 100 eq) in DMSO (8 mL) was added [(lS,4R)-7,7- dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (43.6 mg, 188 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was heated to 50°C and stirred for 96 hours. After cooling to room temperature, the mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75*30mm*3um ; mobile phase: [H2O(0.1% TFA)-ACN];gradient:30%-60% B over 8.0 min) to give Compound S-190M (25.4 mg, 21.9 pmol, 11.7% yield) as a white solid. MS: (M+H): 1156.0 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.84 - 0.86 (m, 8 H) 0.89 (s, 1 H) 0.91 - 0.95 (m, 1 H) 1.09 (br dd, J=13.6, 7.2 Hz, 2 H) 1.15 (br d, J=6.0 Hz, 3 H) 1.22 - 1.31 (m, 18 H) 1.39 - 1.44 (m, 2 H) 1.45 - 1.50 (m, 2 H) 1.53 - 1.58 (m, 2 H) 1.95 (br dd, .7=12.0, 6.0 Hz, 1 H) 2.05 (br s, 1 H) 2.08 (br d, .7=6,4 Hz, 1 H) 2.17 - 2.21 (m, 2 H) 2.39 - 2.46 (m, 2 H) 2.47 - 2.52 (m, 1 H) 2.53 - 2.62 (m, 1 H) 2.78 (br dd, J=15.2, 3.2 Hz, 1 H) 3.76 - 3.82 (m, 2 H) 3.89 (br s, 1 H) 3.93 - 4.01 (m, 2 H) 4.17 - 4.20 (m, 1 H) 4.23 (br d, J=8.8 Hz, 1 H) 4.28 - 4.30 (m, 2 H) 4.32 (s, 1 H) 4.35 - 4.40 (m, 1 H) 4.50 (br d, J=8.4 Hz, 1 H) 4.56 (br d, .7=5,2 Hz, 3 H) 4.96 (br d, J=7.6 Hz, 1 H) 5.00 (br dd, .7=8.4, 3.2 Hz, 1 H) 5.10 (br dd, .7=8.4, 4.4 Hz, 1 H) 5.35 - 5.39 (m, 1 H) 6.75 (d, J=8.4 Hz, 2 H) 7.10 - 7.16 (m, 2 H) 7.17 - 7.24 (m, 1 H) 7.50 (br d, J=8.4 Hz, 1 H) 7.71 (br t, .7=6,4 Hz, 1 H) 7.85 (br d, J=8.0 Hz, 1 H) 8.26 (br t, .7=7.6 Hz, 1 H) 8.67 (br d, J=5.6 Hz, 1 H) 8.74 (br d, J=8.4 Hz, 1 H).

[0353] To a solution of pneumocandin bO (200 mg, 187 pmol, 1.00 eq) in DMSO (8 mL) were added pyridin-3-ylmethanol (18.7 mmol, 1.81 mL, 100 eq) and [(lS,4R)-7,7-dimethyl- 2-oxo-norbornan-l-yl]methanesulfonic acid (43.6 mg, 187 pmol, 1.00 eq). The reaction mixture was heated to 50°C and stirred for 96 hrs. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN]; gradient:25%-55% B over 8.0 min) to afford Compound S- 190U (15.3 mg, 13.23 pmol, 7.05% yield, CF3COOH) as a white solid. MS (M+H): 1156.6 ; ’H NMR: DMSO 400 MHz: 5 ppm 0.9 (dt, J=6.4, 3.2 Hz, 8 H) 0.9 (s, 1 H) 0.9 - 1.0 (m, 1 H) 1.0 - 1.1 (m, 2 H) 1.2 (br d, J=6.0 Hz, 2 H) 1.2 - 1.2 (m, 3 H) 1.3 (br s, 10 H) 1.3 - 1.4 (m, 1 H) 1.4 - 1.4 (m, 1 H) 1.4 - 1.5 (m, 1 H) 1.5 - 1.6 (m, 2 H) 2.0 (dt, J=12.8, 6.4 Hz, 2 H) 2.0 - 2.1 (m, 3 H) 2.1 - 2.3 (m, 3 H) 2.4 - 2.5 (m, 2 H) 2.8 (br dd, J=15.6, 3.6 Hz, 1 H) 3.8 - 3.8 (m, 2 H) 3.9 - 4.0 (m, 2 H) 4.1 - 4.2 (m, 2 H) 4.3 - 4.3 (m, 2 H) 4.3 - 4.4 (m, 2 H) 4.5 (br dd, J=12.4, 5.2 Hz, 1 H) 4.5 - 4.6 (m, 3 H) 4.7 - 4.8 (m, 1 H) 5.0 (br dd, J=8.0, 3.2 Hz, 1 H) 5.1 (dd, J=8.4, 4.0 Hz, 1 H) 5.3 (dd, J=9.2, 1.6 Hz, 1 H) 6.8 (br d, J=8.4 Hz, 2 H) 7.1 (d, J=8.4 Hz, 2 H) 7.5 (br d, J=8.4 Hz, 1 H) 7.8 (dd, J=7.6, 5.6 Hz, 1 H) 8.4 (br d, J=8.0 Hz, 1 H) 8.5 (br d, J=9.2 Hz, 1 H) 8.7 (br d, J=6.4 Hz, 1 H) 8.8 (s, 1 H).

[0354] Example 22 (Compound S-040):

[0355] S-040

[0356] To a solution of pneumocandin bO (403 mg, 378 umol, 1 eq) in acetic acid (HOAc) (10 mL) and TFA (2 mL) was added NaBH3CN (250 mg, 3.97 mmol, 10.5 eq) in one portion at 20°C under N2atmosphere. The reaction mixture was stirred at 20 °C for 16 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna 80*30mm*3pm;mobile phase: [water(TFA)-ACN];B%: 30%-60%,8min) to give crude product (~50 mg, -80% purity). The crude product was further purified by special prep-HPLC (TFA condition: column: C18-4 150*30mm*5pm;mobile phase: [water(TFA)-ACN];B%: 35%- 55%,20minutes) to give Compound S-040 (23 mg) as a white solid. MS (M+H): 1049.6 ; ‘H NMR: DMS0400 MHz: 5 ppm 0.81 - 0.85 (m, 11 H) 0.86 - 0.92 (m, 1 H) 1.02 - 1.06 (m, 4 H) 1.19 - 1.26 (m, 14 H) 1.39 - 1.46 (m, 4 H) 1.60 - 1.72 (m, 1 H) 1.79 - 1.87 (m, 3 H) 2.02 - 2.09 (m, 3 H) 2.18 - 2.26 (m, 2 H) 2.43 (br dd, 7=15.2, 4.4 Hz, 1 H) 2.91 (br d, .7=13.2 Hz, 1 H) 3.39 (br dd, 7=12.0, 1.6 Hz, 1 H) 3.52 - 3.60 (m, 1 H) 3.73 (br d, 7=2.4 Hz, 1 H) 3.78 (br d, 7=4.4 Hz, 1 H) 3.85 - 3.92 (m, 1 H) 3.95 - 4.01 (m, 2 H) 4.10 - 4.15 (m, 3 H) 4.26 - 4.34 (m, 3 H) 4.41 (br s, 1 H) 4.67 - 4.74 (m, 1 H) 4.79 (br d, 7=5.6 Hz, 1 H) 4.87 (br dd, 7=8.8, 3.2 Hz, 1 H) 4.91 (br d, 7=6.0 Hz, 1 H) 5.00 - 5.05 (m, 1 H) 5.09 (br d, 7=5.6 Hz, 1 H) 5.15 (br d, 7=4.0 Hz, 1 H) 5.17 (d, 7=3.2 Hz, 1 H) 5.25 (d, 7=4.8 Hz, 1 H) 6.63 - 6.76 (m, 3 H) 7.01 (d, 7=8.8 Hz, 2 H) 7.19 (br s, 1 H) 7.26 - 7.42 (m, 2 H) 7.64 (br d, 7=5.6 Hz, 1 H) 8.02 - 8.15 (m, 2 H) 9.15 (s, 1 H) 9.29 (s, 1 H).

[0357] S-190C

[0358] To a mixture of pneumocandin bO (200 mg, 188 pmol, 1.00 eq) and phenylmethanethiol (893 mg, 7.19 mmol, 38.3 eq) in DMSO (8 mL) was added [(lS,4R)-7,7- dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (43.6 mg, 188 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex Luna C18 75*30mm*3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:40%-70% B over 8.0 min) to give Compound S-190C (39.5 mg, 37.1 pmol, 11.9% yield) as a white solid. MS (M+H): 1171.6 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.87 (dt, J=6.4, 3.6 Hz, 8 H) 0.91 (s, 1 H) 0.92 - 0.96 (m, 1 H) 1.09 (dt, J=13.6, 7.2 Hz, 2 H) 1.14 - 1.19 (m, 3 H) 1.22 - 1.36 (m, 13 H) 1.40 - 1.45 (m, 1 H) 1.46 - 1.51 (m, 1 H) 1.53 - 1.60 (m, 2 H) 1.91 - 2.02 (m, 2 H) 2.03 - 2.09 (m, 1 H) 2.14 (br t, J=7.2 Hz, 3 H) 2.21 - 2.28 (m, 1 H) 2.45 (br dd, J=12.8, 7.1 Hz, 1 H) 2.53 (br dd, J=15.6, 9.6 Hz, 1 H) 2.83 (br dd, J=15.2, 3.6 Hz, 1 H) 3.77 - 3.83 (m, 2 H) 3.83 - 3.87 (m, 1 H) 3.90 - 3.99 (m, 2 H) 4.00 - 4.07 (m, 1 H) 4.09 - 4.15 (m, 1 H) 4.19 - 4.23 (m, 1 H) 4.25 (br d, J=3.6 Hz, 1 H) 4.30 (s, 2 H) 4.35 - 4.43 (m, 2 H) 4.48 (ddd, J=12.4, 8.0, 4.8 Hz, 1 H) 4.55 - 4.63 (m, 3 H) 5.00 (br dd, J=8.4, 3.2 Hz, 1 H) 5.13 (br dd, J=8.4, 3.6 Hz, 1 H) 5.29 - 5.34 (m, 1 H) 6.77 (d, J=8.4 Hz, 2 H) 7.16 (br d, J=8.4 Hz, 2 H) 7.21 (br d, J=7.2 Hz, 1 H) 7.28 (br t, J=7.6 Hz, 2 H) 7.39 (br d, J=7.6 Hz, 2 H) 7.51 (br d, J=8.4 Hz, 1 H) 7.80 (br d, J=9.6 Hz, 1 H) 8.06 (br d, J=8.0 Hz, 1 H) 8.39 (br d, J=9.6 Hz, 1 H) 8.67 (br d, J=8.4 Hz, 1 H). Example 24 (Compound S-190S):

[0359] To a solution of pneumocandin bO (200 mg, 187 pmol, 1 eq) in DMSO (8 mL) were added phenylmethanol (2.03 g, 18.7 mmol, 100 eq) and [(IS, 4R)-7,7-dimethyl-2-oxo- norboman-l-yl]methanesulfonic acid (43 mg, 187 pmol, 1 eq) in one portion at 20°C. The reaction mixture was heated to 30°C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD Ci8150 x 40mm x 10pm;mobile phase: [H2O(10mM NH4HC03)-ACN];gradient:50%-80% B over 8.0 min) to give crude product (90 mg). The crude product was further purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:30%-60% B over 8.0 min) to give pure compound S-190S (35.8 mg, 43.2 pmol) as a white solid. MS (M+H): 1155.5 ; ’H NMR: MeOD 400 MHz. 5 = ppm 8.75 (br d, J= 8.8 Hz, 1 H), 8.38 (d, J= 92 Hz, 1 H), 7.77 (br d, J= 9.6 Hz, 1 H), 7.51 (br d, J= 8.0 Hz,

[0360] 1 H), 7.40 - 7.35 (m, 2 H), 7.34 - 7.22 (m, 3 H), 7.14 (d, J= 8.4 Hz, 2 H), 6.75 (d, J= 8.4 Hz,

[0361] 2 H), 5.29 - 5.22 (m, 1 H), 5.13 - 5.07 (m, 1 H), 4.97 (br d, J= 3.2 Hz, 1 H), 4.68 - 4.53 (m, 5 H), 4.48 - 4.42 (m, 1 H), 4.41 - 4.25 (m, 5 H), 4.22 - 4.10 (m, 2 H), 4.06 - 3.91 (m, 2 H), 3.84 - 3.74 (m, 2 H), 2.85 (br dd, J= 3.2, 15.2 Hz, 1 H), 2.52 (br dd, J= 9.6, 15.2 Hz, 1 H), 2.42 (br dd, J= 12, 13.2 Hz, 1 H), 2.21 (br dd, J= 52, 12.8 Hz, 1 H), 2.12 (t, J= 7.2 Hz, 2 H), 2.09 - 1.89 (m, 4 H), 1.55 - 1.20 (m, 18 H), 1.15 (br d, J= 6.0 Hz, 2 H), 1.12 - 1.01 (m, 2 H), 0.95 - 0.83 (m, 10 H).

[0362] To a solution of pneumocandin bO (500 mg, 469.3 pmol, 1.00 eq) in DMSO (8 mL) was added 2-phenylethanamine (1.71 g, 14.0 mmol, 30.0 eq) and [(lS,4R)-7,7-dimethyl-2- oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) at 20°C. The reaction mixture was heated to 30°C and stirred for 40 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 min) and prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:20%-50% B over 8.0 min) to give Compound S-190W (22.2 mg, 19.0 pmol) as a white solid. MS (M+H): 1168.6 ; ’H NMR: DMSO 400 MHz. 5 = ppm 8.28 (dd, J= 2.0, 7.6 Hz, 1 H), 8.18 (d, J= 8.4 Hz, 1 H), 7.78 (d, J= 7.6 Hz, 1 H), 7.34 - 7.28 (m, 2 H), 7.27 - 7.20 (m, 3 H), 7.09 (d, J= 8.4 Hz, 2 H), 6.64 - 6.58 (m, 2 H), 4.75 (t, J= 6.8 Hz, 1 H), 4.61 - 4.50 (m, 2 H), 4.46 - 4.41 (m, 1 H), 4.36 (d, J= 8.6 Hz, 2 H), 4.25 (J = 4.4, 8.4 Hz, 1 H), 4.17 - 4.05 (m, 4 H), 3.94 - 3.87 (m, 2 H), 3.70 (s, 1 H), 3.64 - 3.57 (m, 2 H), 3.13 - 2.97 (m, 3 H), 2.93 - 2.86 (m, 2 H), 2.72 - 2.63 (m, 1 H), 2.35 - 2.29 (m, 1 H), 2.18 (dd, J= 8.6, 14.8 Hz, 2 H), 2.10 - 2.04 (m, 2 H), 1.97 - 1.76 (m, 3 H), 1.46 - 1.34 (m, 4 H), 1.25 - 1.10 (m, 18 H), 1.06 - 0.96 (m, 2 H), 0.88 - 0.83 (m, 1 H), 0.80 - 0.76 (m, 10 H).

[0363]

[0364] S-190J1

[0365] To a solution of pneumocandin bO (300 mg, 281 pmol, 1.00 eq) in DMSO (3 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norbornan-l-yl] methanesulfonic acid (65.4 mg, 281 pmol, 1.00 eq) and 2-(methyl(propyl)amino)ethan-l-ol (330 mg, 2.82 mmol, 10.0 eq) in one portion at 25°C. The reaction mixture was heated to 80°C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 min) to give Compound S-190J1 (20 mg, 17.1 pmol, 6.10% yield, TFA) as a white solid. MS: (M+H): 1164.3 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.9 - 0.9 (m, 8 H) 0.9 (s, 1 H) 0.9 - 1.0 (m, 4 H) 1.0 - 1.1 (m, 1 H) 1.1 - 1.1 (m, 1 H) 1.2 - 1.2 (m, 1 H) 1.3 (br s, 1 H) 1.3 (br d, J=4.4 Hz, 3 H) 1.3 (br d, J=5.2 Hz, 9 H) 1.4 (br d, J=2.4 Hz, 1 H) 1.4 (br s, 1 H) 1.4 - 1.4 (m, 1 H) 1.4 (br d, J=6.4 Hz, 1 H) 1.5 (br d, J=6.4 Hz, 1 H) 1.5 - 1.5 (m, 1 H) 1.6 (br s, 2 H) 1.7 (br dd, J=13.6, 6.8 Hz, 2 H) 2.0 - 2.0 (m, 1 H) 2.0 - 2.1 (m, 1 H) 2.1 - 2.2 (m, 1 H) 2.2 (q, J=7.6 Hz, 2 H) 2.3 - 2.4 (m, 2 H) 2.5 - 2.6 (m, 1 H) 2.6 - 2.7 (m, 1 H) 2.9 - 3.0 (m, 1 H) 3.0 (br d, J=8.4 Hz, 1 H) 3.0 - 3.1 (m, 1 H) 3.1 (br s, 1 H) 3.1 - 3.2 (m, 1 H) 3.4 - 3.6 (m, 1 H)

[0366] 3.8 - 4.0 (m, 5 H) 4.2 - 4.3 (m, 3 H) 4.3 - 4.4 (m, 2 H) 4.4 - 4.5 (m, 2 H) 4.5 - 4.5 (m, 1 H) 4.6 (br s, 2 H) 4.6 - 4.6 (m, 1 H) 4.7 - 4.8 (m, 1 H) 4.8 - 4.8 (m, 1 H) 5.0 (td, J=8.8, 5.2 Hz, 1 H)

[0367] 6.8 (d, J=8.4 Hz, 2 H) 7.2 - 7.2 (m, 2 H) 7.6 (br d, J=8.0 Hz, 1 H) 7.6 (br d, J=8.8 Hz, 1 H)

[0368] 7.9 (br d, J=8.8 Hz, 1 H) 8.1 (br d, J=8.4 Hz, 1 H) 8.2 - 8.2 (m, 1 H).

[0369] To a solution of pneumocandin bO (1.00 g, 938 umol, 1.00 eq) in MeCN (40 mL) were added phenylboronic acid (240 mg, 1.97 mmol, 2.10 eq) and 2-(diethylamino)ethane-l- thiol (262 mg, 1.97 mmol, 2.09 eq) at -20°C. The reaction mixture was stirred at -20°C for 0.5 hours. Then trifluoromethanesulfonic acid (401 mg, 2.68 mmol, 236 uL, 2.85 eq) was added to the reaction mixture. The reaction mixture was warmed to 25°C and stirred for 16 hours. Nine parallel reactions were combined to work-up. Saturated Sodium acetate aqueous was added to the reaction mixture and stirred for 1 hour. Some white solid was appeared and the solid was filtered and the filter cake was washed with MeCN (50 mL x 3). The residue was purified by prep-HPLC (column: Phenomenex luna Ci8(250 x 70mm, 10 um); mobile phase: [water(TFA)-ACN]; B%: 30%-65%, 20min) to give crude product (900 mg), which was purified by prep-HPLC (column: Waters Xbridge Prep OBD Ci8150 x 40mm x 10pm;mobile phase: [water( NH4HCO3)-ACN];B%: 45%-65%,8min) again to give Intermediate 1 (402.2 mg, 336 pmol, 98.8% purity) as a white solid.

[0370] To a solution of Intermediate 1 (300 mg, 254 pmol, 1.00 eq) in DMF (3 mL) was added NaHCO3(42.7 mg, 508 pmol, 2.00 eq), then Mel (108 mg, 762 pmol, 3.00 eq) was added to the mixture at 25°C. The reaction mixture was stirred at 25°C for 16 hours. LCMS showed the starting material was consumed completely and desired MS observed. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 min) to give Compound S- 190A (26.5 mg, 20.2 pmol, 7.96% yield, TFA) as a white solid. MS: (M+H): 1194.7 ; ’H NMR: DMSO 400MHz. 5 ppm 3.3 - 3.3 (m, 3 H) 3.6 (s, 2 H) 3.7 - 3.8 (m, 2 H) 3.9 (br d, J=3.6 Hz, 2 H) 4.0 (br d, J=9.6 Hz, 1 H) 4.1 (br dd, 7=7.6, 4.0 Hz, 2 H) 4.2 (br s, 2 H) 4.3 (br dd, J=11.2, 7.2 Hz, 1 H) 4.4 (br s, 2 H) 4.7 (br d, 7=6.4 Hz, 1 H) 4.8 (br d, 7=5.2 Hz, 2 H) 4.9 (br dd, 7=8.4, 4.4 Hz, 1 H) 5.0 (br d, 7=4.8 Hz, 1 H) 5.1 - 5.2 (m, 3 H) 5.3 (br d, 7=10.0 Hz, 1 H) 5.3 (br d, 7=4.4 Hz, 1 H) 6.7 (d, 7=8.4 Hz, 2 H) 6.7 (br s, 1 H) 7.0 (d, 7=8.4 Hz, 2 H) 7.1 (br s, 1 H) 7.2 (br d, 7=9.2 Hz, 1 H) 7.4 (br d, 7=10.4 Hz, 1 H) 8.2 - 8.3 (m, 1 H) 8.4 (br d, 7=8.4 Hz, 1 H) 8.5 (br d, 7=9.2 Hz, 1 H) 9.3 (s, 1 H).

[0371] Example 28 (Compound S-190BB1):

[0372] To a mixture of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) and (4- bromophenyl)methanol (2.19 g, 11.7 mmol, 25.0 eq) in DMSO (5 mL) was added [(1S,4R)- 7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex luna Cl 8 100*40mm*3 pm;mobile phase: [H2O(0.1%TFA)-ACN];gradient:45%-75% B over 8.0 min) to give Compound S-190BB1 (100 mg, 81.0 pmol, 17.26% yield) as a white solid. MS (M+H): 1233 ;. ’H NMR: MeOD 400 MHz. 5 ppm 0.86 (dt, J=6.8, 3.6 Hz, 8 H) 0.89 (s, 1 H) 0.90 - 0.95 (m, 1 H) 1.01 - 1.07 (m, 1 H) 1.07 - 1.12 (m, 1 H) 1.12 - 1.17 (m, 3 H) 1.20 - 1.35 (m, 14 H) 1.37 - 1.42 (m, 1 H) 1.47 (br s, 1 H) 1.49 - 1.59 (m, 2 H) 1.90 - 2.07 (m, 4 H) 2.07 - 2.14 (m, 2 H) 2.17 - 2.27 (m, 1 H) 2.39 - 2.54 (m, 2 H) 2.82 (dd, J=15.6, 3.6 Hz, 1 H) 3.74 - 3.83 (m, 2 H) 3.95 (br dd, J=11.2, 3.2 Hz, 1 H) 3.98 - 4.06 (m, 1 H) 4.07 - 4.15 (m, 1 H) 4.21 - 4.25 (m, 1 H) 4.26 - 4.31 (m, 3 H) 4.33 (br d, J=10.0 Hz, 1 H) 4.37 (br dd, J=9.2, 4.4 Hz, 1 H) 4.42 (dd, J=11.6, 6.4 Hz, 1 H) 4.49 - 4.56 (m, 3 H) 4.57 - 4.64 (m, 2 H) 4.97 (dd, J=8.4, 3.6 Hz, 1 H) 5.11 (dd, J=8.4, 4.0 Hz, 1 H) 5.22 (dd, J=9.6, 2.0 Hz, 1 H) 6.73 - 6.79 (m, 2 H) 7.14 (d, J=8.4 Hz, 2 H) 7.31 (d, J=8.4 Hz, 2 H) 7.43 - 7.48 (m, 2 H) 7.50 (d, J=8.4 Hz, 1 H) 7.78 (br d, J=9.6 Hz, 1 H) 8.35 (d, J=9.6 Hz, 1 H) 8.68 (br d, J=8.4 Hz, 1 H).

[0373] S-190AA1

[0374] To a mixture of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) and (3- bromophenyl)methanol (2.19 g, 11.7 mmol, 25.0 eq) in DMSO (8 mL) was added [(1S,4R)- 7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: 3_Phenomenex Luna C18 75 x 30mm x 3um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 45%-75% B over 8.0 min) to give Compound S-190AA1 (100 mg, 81.0 pmol, 17.26% yield) as a white solid.. MS (M+H): 1233.6 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.83 - 0.88 (m, 8 H) 0.89 (s, 1 H) 0.90 - 0.95 (m, 1 H) 1.01 - 1.06 (m, 1 H) 1.10 (br dd, J=13.6, 6.8 Hz, 1 H) 1.19 (br s, 3 H) 1.20 - 1.37 (m, 14 H) 1.39 - 1.44 (m, 1 H) 1.44 - 1.50 (m, 1 H) 1.50 - 1.59 (m, 2 H) 1.93 - 2.02 (m, 2 H) 2.04 - 2.08 (m, 1 H) 2.14 (br t, J=7.2 Hz, 2 H) 2.18 - 2.27 (m, 1 H) 2.43 (br dd, J=12.8, 7.2 Hz, 1 H) 2.49 (br dd, J=15.6, 9.6 Hz, 1 H) 2.81 (dd, J=15.6, 3.6 Hz, 1 H) 3.74 - 3.84 (m, 2 H) 3.95 (br dd, J=11.2, 3.2 Hz, 1 H) 3.99 - 4.07 (m, 1 H) 4.10 - 4.22 (m, 2 H) 4.32 (s, 3 H) 4.33 - 4.40 (m, 2 H) 4.40 - 4.49 (m, 1 H) 4.51 - 4.57 (m, 3 H) 4.58 - 4.67 (m, 2 H) 4.98 (br dd, J=8.4, 3.2 Hz, 1 H) 5.10 (dd, J=8.4, 4.0 Hz, 1 H) 5.24 (dd, J=9.6, 2.0 Hz, 1 H) 6.72 - 6.79 (m, 2 H) 7.10 - 7.18 (m, 2 H) 7.19 - 7.27 (m, 1 H) 7.31 - 7.36 (m, 1 H) 7.41 (br d, J=8.0 Hz, 1 H) 7.50 (br d, J=8.4 Hz, 1 H) 7.54 - 7.58 (m, 1 H) 7.78 (br d, J=9.6 Hz, 1 H) 8.15 (br d, J=8.0 Hz, 1 H) 8.37 (br d, J=9.6 Hz, 1 H) 8.69 (br d, J=8.4 Hz, 1 H).

[0375] S-190Z1

[0376] To a mixture of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) and (2- bromophenyl)methanol (2.19 g, 11.7 mmol, 25.0 eq) in DMSO (5 mL) was added [(1S,4R)- 7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex luna Cl 8 100*40 mm*3 um;mobile phase: [H2O(0.1%TFA)-ACN]; gradient:45%-75% B over 8.0 min) to give Compound S-190Z1 (100 mg, 81.0 pmol, 17.26% yield) as a white solid. MS (M+H): 1235.5 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.81 - 0.88 (m, 8 H) 0.89 (s, 1 H) 0.90 - 0.96 (m, 1 H) 0.98 - 1.05 (m, 1 H)

[0377] 1.10 (br dd, J=13.6, 6.8 Hz, 1 H) 1.16 (br d, J=6.0 Hz, 3 H) 1.19 - 1.36 (m, 14 H) 1.36 - 1.41 (m, 1 H) 1.43 - 1.49 (m, 1 H) 1.52 - 1.62 (m, 2 H) 1.89 - 1.99 (m, 1 H) 2.00 - 2.14 (m, 3 H) 2.14 - 2.27 (m, 3 H) 2.37 - 2.55 (m, 2 H) 2.83 (dd, J=15.2, 3.6 Hz, 1 H) 3.71 - 3.85 (m, 2 H) 3.95 (br dd, J=11.2, 3.2 Hz, 1 H) 3.99 - 4.10 (m, 1 H) 4.17 - 4.27 (m, 2 H) 4.32 (d, J=2.4 Hz, 1 H) 4.33 - 4.40 (m, 2 H) 4.41 - 4.49 (m, 1 H) 4.51 - 4.56 (m, 2 H) 4.56 - 4.59 (m, 1 H) 4.62 (br d, J=8.8 Hz, 1 H) 4.64 - 4.69 (m, 1 H) 4.70 - 4.76 (m, 1 H) 4.98 (dd, J=8.4, 3.2 Hz, 1 H)

[0378] 5.11 (dd, J=8.4, 3.6 Hz, 1 H) 5.33 (dd, J=9.6, 2.0 Hz, 1 H) 6.71 - 6.79 (m, 2 H) 7.10 - 7.20 (m, 3 H) 7.30 - 7.37 (m, 1 H) 7.47 - 7.56 (m, 2 H) 7.58 (dd, J=7.6, 1.2 Hz, 1 H) 7.78 (br d, J=9.6 Hz, 1 H) 8.22 (br d, J=8.0 Hz, 1 H) 8.41 (br d, J=9.6 Hz, 1 H) 8.70 (br d, J=8.4 Hz, 1 H).

[0379] S-190EE1

[0380] To a solution of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) in DMSO (1 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) and 2-(4-bromophenyl)ethan-l-ol (2.36 g, 11.7 mmol, 25.0 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: 3_Phenomenex Luna C18 75 x 30mm x 3um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 45%-75% B over 8.0 min) to give Compound S-190EE1 (100 mg, 80.1 pmol, 17.0% yield) as a white solid. MS (M+H): 1249.6 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.9 (dt, J=6.4, 3.2 Hz, 8 H) 0.9 (s, 1 H) 0.9 (d, .7=6,4 Hz, 1 H) 1.0 - 1.1 (m, 1 H) 1.1 - 1.1 (m, 1 H) 1.2 (d, .7=6.0 Hz, 3 H) 1.2 - 1.2 (m, 2 H) 1.3 (br d, .7=4.8 Hz, 7 H) 1.3 (br s, 3 H) 1.3 (br s, 1 H) 1.4 (br d, J=5.6 Hz, 1 H) 1.4 - 1.4 (m, 1 H) 1.4 - 1.5 (m, 1 H) 1.5 - 1.6 (m, 2 H) 1.9 - 2.0 (m, 3 H) 2.0 - 2.1 (m, 1 H) 2.2 - 2.3 (m, 3 H) 2.4 - 2.5 (m, 1 H) 2.5 - 2.5 (m, 1 H) 2.8 - 2.9 (m, 3 H) 3.6 - 3.7 (m, 1 H) 3.7 - 3.8 (m, 3 H) 3.9 - 4.0 (m, 2 H) 4.0 - 4.1 (m, 1 H) 4.2 - 4.3 (m, 4 H) 4.3 - 4.4 (m, 2 H) 4.4 - 4.5 (m, 1 H) 4.5 - 4.6 (m, 3 H) 5.0 (dd, J=8.4,

[0381] 3.2 Hz, 1 H) 5.1 (dd, J=8.4, 4.0 Hz, 1 H) 5.2 (dd, J=9.2, 2.0 Hz, 1 H) 6.7 - 6.8 (m, 2 H) 7.1 -

[0382] 7.2 (m, 4 H) 7.4 (d, J=8.4 Hz, 2 H) 7.5 (d, J=8.4 Hz, 1 H) 7.8 (br d, J=9.6 Hz, 1 H) 8.2 (d, J=8.4 Hz, 1 H) 8.3 (d, J=9.6 Hz, 1 H) 8.7 (br d, J=8.4 Hz, 1 H). Example 32 (Compound S-190DD1):

[0383] S-190DD1

[0384] To a solution of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) in DMSO (1 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) and 2-(3-bromophenyl)ethan-l-ol (2.36 g, 11.7 mmol, 25.0 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: 3_Phenomenex Luna C18 75 x 30mm x 3um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 45%-75% B over 8.0 min) to give Compound S-190DD1 (50 mg, 40 pmol, 8.53% yield) as a white solid. MS (M+H): 1249.6 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.9 (dt, J=6.4, 3.6 Hz, 8 H) 0.9 (s, 1 H) 0.9 - 0.9 (m, 1 H) 1.0 - 1.1 (m, 1 H) 1.1 - 1.1 (m, 1 H) 1.2 (br d, .7=6.0 Hz, 3 H) 1.2 - 1.2 (m, 2 H) 1.3 (br s, 11 H) 1.4 (br s, 1 H) 1.4 - 1.4 (m, 1 H) 1.4 - 1.5 (m, 1 H) 1.6 (br d, .7=13.6 Hz, 2 H) 2.0 - 2.0 (m, 2 H) 2.1 (br d, J=2.0 Hz, 1 H) 2.2 - 2.3 (m, 3 H) 2.4 - 2.5 (m, 1 H) 2.5 - 2.5 (m, 1 H) 2.8 - 2.8 (m, 1 H) 2.9 - 2.9 (m, 1 H) 3.7 (dt, .7=9.6, 7.2 Hz, 1 H) 3.7 - 3.8 (m, 3 H) 3.9 (br dd, J=10.8, 2.4 Hz, 1 H) 4.0 - 4.0 (m, 1 H) 4.1 (br t, J=8.4 Hz, 1 H) 4.3 (s, 3 H) 4.3 - 4.4 (m, 2 H) 4.4 - 4.5 (m, 1 H) 4.5 - 4.6 (m, 3 H) 5.0 (br dd, J=8.4, 3.2 Hz, 1 H) 5.1 (br dd, J=8.0, 3.6 Hz, 1 H) 5.2 (dd, .7=9.2, 1.6 Hz, 1 H) 6.7 - 6.8 (m, 2 H) 7.1 - 7.2 (m, 3 H) 7.2 (br d, .7=4,0 Hz, 1 H) 7.3 (br d, J=7.2 Hz, 1 H) 7.4 (s, 1 H) 7.5 (br d, J=8.4 Hz, 1 H) 7.8 (br d, J=9.6 Hz, 1 H) 8.2 (br d, J=8.0 Hz, 1 H) 8.3 (br d, J=9.2 Hz, 1 H) 8.7 (br d, J=8.4 Hz, 1 H).

[0385] S-190CC1

[0386] To a solution of pneumocandin bO (500 mg, 469 pmol, 1.00 eq) in DMSO (1 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1.00 eq) and 2-(2-bromophenyl)ethan-l-ol (2.36 g, 11.7 mmol, 25.0 eq) in one portion at 25°C. The reaction was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: 3_Phenomenex Luna C18 75 x 30mm x 3um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 45%-75% B over 8.0 min) to give Compound S-190CC1 (100 mg, 80.11 pmol, 17.07% yield) as a white solid. MS (M+H): 1249.3 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.9 (dt, 7=6.4, 3.6 Hz, 8 H) 0.9 (s, 1 H) 0.9 (br d, 7=6.4 Hz, 1 H) 1.0 - 1.1 (m, 3 H) 1.2 (br d, 7=6.0 Hz, 2 H) 1.2 - 1.2 (m, 2 H) 1.2 - 1.3 (m, 12 H) 1.4 - 1.4 (m, 2 H) 1.4 - 1.5 (m, 1 H) 1.5 - 1.6 (m, 2 H) 1.9 - 2.0 (m, 3 H) 2.0 - 2.1 (m, 1 H) 2.2 - 2.3 (m, 3 H) 2.4 - 2.4 (m, 1 H) 2.5 - 2.5 (m, 1 H) 2.8 (dd, 7=15.2, 3.6 Hz, 1 H) 3.0 - 3.1 (m, 2 H) 3.7 - 3.7 (m, 1 H) 3.8 - 3.8 (m, 2 H) 4.0 (br dd, 7=10.8, 2.8 Hz, 1 H) 4.0 - 4.1 (m, 1 H) 4.1 (br t, 7=7.2 Hz, 1 H) 4.3 - 4.3 (m, 3 H) 4.4 (br dd, 7=9.6, 3.6 Hz, 2 H) 4.4 - 4.5 (m, 1 H) 4.5 - 4.6 (m, 3 H) 5.0 (br dd, 7=8.4, 3.2 Hz, 1 H) 5.1 (dd, 7=8.4, 3.6 Hz, 1 H) 5.2 (dd, 7=9.2, 2.0 Hz, 1 H) 6.8 (br d, 7=8.4 Hz, 2 H) 7.1 - 7.2 (m, 3 H) 7.3 (t, 7=7.2 Hz, 1 H) 7.3 - 7.4 (m, 1 H) 7.5 - 7.5 (m, 2 H) 7.8 (br d, 7=9.6 Hz, 1 H) 8.2 (br d, 7=8.0 Hz, 1 H) 8.3 (br d, 7=9.2 Hz, 1 H) 8.7 (br d, 7=8.4 Hz, 1 H). Example 34 (Compound S-190L):

[0387] S-190L

[0388] Oxetan-2-one (500 mg, 6.9 mmol, 436 pL, 1.00 eq) was added to a solution of N- methylmethanamine (2 M, 86 mL, 24.8 eq) at 0°C, the solution was stirred at 15°C for 10 minutes. The mixture was concentrated under reduce pressure to give Reagent 1 (800 mg, 6.8 mmol, 98.4% yield) as a light yellow gum.

[0389] To a solution of pneumocandin bO (270 mg, 253 pmol, 1.00 eq) and Reagent 1 (593 mg, 5.07 mmol, 20.0 eq) in DMSO (5 mL) was added (lS)-(+)-10-camphorsulfonic acid (58.8 mg, 253 pmol, 1.00 eq), the result mixture was stirred at 30°C for 10 hours. The solid was filtered and the filtrate was purified by prep-HPLC(column: Phenomenex Luna Cl 8 75*30mm*3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:35%-65% B over 8.0 min) to give the Compound S-190L (90 mg, 78.1 pmol, 30.8% yield) as a white solid. MS: (M+H): 1164.7 ; 1H NMR: DMSO 400MHz 5 = ppm 9.29 (br d, J = 6.4 Hz, 1H), 8.26 - 8.17 (m, 2H), 8.06 (d, J = 10.0 Hz, 1H), 7.40 (br d, J = 9.6 Hz, 1H), 7.26 - 7.20 (m, 2H), 7.02 (d, J

[0390] = 8.4 Hz, 3H), 6.79 - 6.65 (m, 4H), 4.97 - 4.86 (m, 4H), 4.84 - 4.74 (m, 2H), 4.47 - 4.28 (m, 5H), 4.27 - 4.09 (m, 7H), 4.05 - 3.94 (m, 4H), 3.93 - 3.87 (m, 2H), 3.79 - 3.71 (m, 3H), 3.68 - 3.62 (m, 2H), 3.60 - 3.52 (m, 4H), 2.94 (s, 3H), 2.79 (s, 3H), 2.28 - 2.00 (m, 7H), 1.92 - 1.67 (m, 5H), 1.51 - 1.36 (m, 6H), 1.35 - 1.16 (m, 18H), 1.10 - 0.99 (m, 6H), 0.91 - 0.80 (m, 13H)

[0391] S-190A1

[0392] A solution of 2-(acetylthio)-N,N,N-trimethylethan-l-aminium iodide (5 g, 17.2 mmol, 1.00 eq) in ethanol (220 mL) was degassed and purged with N2for 5 times. Then HC1 (12 M, 8.97 mL, 6.23 eq) was added to the mixture, the mixture was heated to 75°C and stirred for 16 hours under N2atmosphere. After cooling to room temperature, the mixture was concentrated under reduced pressure to dryness. The residue was dissolved in water (10 mL) and lyophilized to afford Reagent 1 (3.8 g, 15.4 mmol, 88.9% yield) as a light yellow solid.

[0393] To a solution pneumocandin bO (400 mg, 375 pmol, 1.00 eq) and Reagent 1 (928 mg, 3.76 mmol, 10.0 eq) in DMSO (1 mL) was added (lS)-(+)-10-camphorsulfonic acid (87.2 mg, 375 pmol, 1.00 eq) at 20°C, the reaction mixture was stirred at 20°C for 10 hours. The mixture was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (Phenomenex luna C18 100*40mm*5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:30%-60% B over 8.0 min) to give Compound S-190A1 (23 mg, 19.7 pmol, 5.25% yield) as a white solid. MS: (M, quaternary ammonium salt): 1166.6 ; 1H NMR: MeOD 400MHz 5 = ppm 8.54 (t, J = 8.8 Hz, 1H), 8.15 (d, J = 9.2 Hz, 1H), 7.71 (d, J = 10.0 Hz, 1H), 7.51 (d, J = 8.4 Hz, 1H), 7.14 (d, J = 8.8 Hz, 1H), 6.75 (d, J = 8.4 Hz, 1H), 5.55 (br d, J = 9.6 Hz, 1H), 5.15 - 5.01 (m, 2H), 4.66 - 4.49 (m, 3H), 4.40 - 4.19 (m, 4H), 4.04 - 3.90 (m, 2H), 3.88 - 3.70 (m, 2H), 3.65 - 3.51 (m, 1H), 3.10 - 3.00 (m, 1H), 2.97 - 2.84 (m, 1H), 2.72 - 2.63 (m, 1H), 2.52 - 2.37 (m, 1H), 2.34 - 2.14 (m, 2H), 2.12 - 1.87 (m, 2H), 1.63 (br d, J = 5.6 Hz, 1H), 1.56 - 1.40 (m, 2H), 1.38 - 1.20 (m, 7H), 1.17 - 1.01 (m, 3H), 0.97 - 0.81 (m, 6H)

[0394] To a solution of pneumocandin bO (400 mg, 375 pmol, 1.00 eq) in DMSO (12 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (106 mg, 457 pmol, 1.00 eq) and 3 -phenylpropane- 1 -thiol (1.72 g, 11.2 mmol, 30.0 eq) in one portion at 15°C, the mixture was degassed and purged with N2for 3 times. The reaction mixture was heated to 30°C and stirred for 16 hours under N2atmosphere. After cooling to room temperature, the crude solvent was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150x40mmxl0pm;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:50%- 80% B over 8.0 min) to give crude product. The crude product was further purified by prep- HPLC (column: Phenomenex luna C18 100x40mmx5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:40%-70% B over 8.0 minutes) to give crude product. The crude product was further purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150x40mmxl0pm;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:55%-75% B over 8.0 min) to give pure Compound S-190Y (47.8 mg, 39.4 pmol, 10.5% yield, 98.98% purity) as a white solid. MS: (M+H): 1200.6 ; ’H NMR: MeOD 400 MHz: 5 = ppm 8.59 (d, J= 8.4 Hz, 1 H), 8.16 (d, J= 8.4 Hz, 1 H), 7.50 (d, J= 8.4 Hz, 1 H), 7.28 - 7.21 (m, 2 H), 7.16 (dd, J = 7.6, 12.4 Hz, 5 H), 6.76 (d, J= 8.4 Hz, 2 H), 5.30 (s, 1 H), 5.14 - 5.07 (m, 1 H), 4.99 (d, J= 3.2 Hz, 1 H), 4.66 - 4.45 (m, 5 H), 4.43 - 4.34 (m, 2 H), 4.33 - 4.26 (m, 2 H), 4.24 (d, J= 3.2 Hz, 1 H), 4.21 - 4.16 (m, 1 H), 4.14 (dd, J= 6.0, 9.2 Hz, 1 H), 4.04 - 3.86 (m, 2 H), 3.77 (d, J = 9.6 Hz, 2 H), 2.80 (dd, J= 3.2, 15.2 Hz, 1 H), 2.73 - 2.63 (m, 3 H), 2.61 - 2.49 (m, 2 H), 2.49 - 2.38 (m, 2 H), 2.23 - 2.04 (m, 5 H), 2.03 - 1.80 (m, 5 H), 1.55 (d, J= 6.8 Hz, 2 H), 1.50 - 1.35 (m, 3 H), 1.35 - 1.19 (m, 13 H), 1.14 (d, J= 6.0 Hz, 3 H), 1.07 (d, J= 7.2, 14.0 Hz, 2 H), 0.97 - 0.78 (m, 10 H).

[0395] To a solution of pneumocandin bO (200 mg, 187 pmol, 1.00 eq) in DMSO (8 mL) were added 2-phenylethanol (2.29 g, 18.7 mmol, 100 eq) and [(lS,4R)-7,7-dimethyl-2-oxo- norboman-l-yl]methanesulfonic acid (43 mg, 187 pmol, 1.00 eq) in one portion at 20°C. The reaction mixture was heated to 30°C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD Ci8150 x 40mm x 10pm;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:45%-75% B over 8.0 min) to give crude product (90 mg). The crude product was further purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 um;mobile phase: [H20(0.04% HC1)- ACN];gradient:30%-60% B over 8.0 min) to give Compound S-190Q (54.4 mg, 46.5 pmol, 54.4% yield) as a white solid. MS (M+H): 1169.5 ;1H NMR: MeOD 400 MHz: 5 = ppm 8.70 (d, J= 8.4 Hz, 1 H), 8.29 (d, J= 92 Hz, 1 H), 7.78 (br d, J= 9.6 Hz, 1 H), 7.51 (d, J= 8.4 Hz, 1 H), 7.28 - 7.20 (m, 4 H), 7.19 - 7.11 (m, 3 H), 6.75 (d, J= 8.4 Hz, 2 H), 5.22 (dd, J = 2.4, 9.6 Hz, 1 H), 5.10 (dd, J= 4.0, 8.4 Hz, 1 H), 4.98 (dd, J= 3.2, 8.4 Hz, 1 H), 4.62 - 4.53 (m, 3 H), 4.47 (dd, J= 6.0, 11.2 Hz, 1 H), 4.40 - 4.31 (m, 2 H), 4.28 (s, 3 H), 4.13 - 4.05 (m, 1 H), 4.05 - 3.93 (m, 2 H), 3.83 - 3.63 (m, 4 H), 2.95 - 2.78 (m, 3 H), 2.54 - 2.39 (m, 2 H), 2.29 - 2.16 (m, 3 H), 2.11 - 1.91 (m, 4 H), 1.63 - 1.53 (m, 2 H), 1.47 - 1.03 (m, 21 H), 0.96 - 0.83 (m, 10 H).

[0396] To a solution of pneumocandin bO (200 mg, 188 pmol, 1 eq) in DMSO (8 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (43 mg, 188 pmol, 1 eq) and 3-phenylpropan-l-ol (18 mmol, 2.5 mL, 100 eq) in one portion at 15 °C, the reaction mixture was degassed and purged with N2for 3 times, then the reaction mixture was heated to 30 °C and stirred for 16 h under N2atmosphere. After cooling to room temperature, the solvent was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150x40mmxl0um;mobile phase: [H2O(10 mM NH4HC03)-ACN];gradient:50%-80% B over 8.0 min) to give Compound 190X (104.9 mg, 87 pmol, 46.6% yield, 98.8% purity) as a white solid. MS: (M+H):l 183.6 ; ’H NMR: MeOD 400 MHz: 5 = ppm 7.24 (d, J= 7.2 Hz, 2 H), 7.20 - 7.11 (m, 5 H), 6.75 (d, J= 8.4 Hz, 2 H), 5.14 (d, J= 2.0 Hz, 1 H), 5.09 (d, J= 3.6 Hz, 1 H), 4.98 (d, J= 2.8 Hz, 1H), 4.63 - 4.52 (m, 3 H), 4.46 (dd, J= 5.6, 11.6 Hz, 1 H), 4.40 - 4.34 (m, 1 H), 4.32 (s, 1 H), 4.28 (s, 3 H), 4.25 - 4.20 (m, 1 H), 4.15 - 4.07 (m, 1 H), 4.06 - 3.99 (m, 1 H), 3.95 (dd, J= 2.8, 10.8 Hz, 1 H), 3.83 - 3.73 (m, 2 H), 3.60 - 3.53 (m, 1 H), 3.48 (d, J= 6.4, 9.6 Hz, 1 H), 2.80 (dd, J= 3.6, 15.2 Hz, 1 H), 2.71 - 2.61 (m, 2 H), 2.54 - 2.38 (m, 2 H), 2.25 - 2.14 (m, 3 H), 2.11 - 1.92 (m, 4 H), 1.91 (s, 2 H), 1.56 (d, J = 6.4 Hz, 2 H), 1.51 - 1.35 (m, 3 H), 1.35 - 1.21 (m, 13 H), 1.17 (d, J= 6.0 Hz, 3 H), 1.12 - 1.02 (m, 2 H), 0.96 - 0.90 (m, 1 H), 0.89 (s, 1 H), 0.88 - 0.80 (m, 9 H).

[0397] To a solution of pneumocandin bO (500 mg, 469 pmol, 1 eq) in DMSO (20 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1 eq) and 2-(diethylamino)ethanol hydrochloride (8.9 g, 46.9 mmol, 100 eq, HC1) in one portion at 15°C, the mixture was degassed and purged with N2for 3 times, then the reaction mixture was heated to 30°C and stirred for 16 hours under N2atmosphere. After cooling to room temperature, the residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150x40mmxl0um;mobile phase: [H2O(10mM NH4HCO3)- ACN];gradient:35%-65% B over 8.0 min) to give Compound 190P (104.5 mg, 88.5 pmol, 18.8% yield, 98.6% purity) as a white solid. MS: (M+H): 1164.8 ; ’H NMR: MeOD 400 MHz: 5 = ppm 7.13 (d, J= 8.4 Hz, 2 H), 6.75 (d, J= 8.4 Hz, 2 H), 5.16 (d, J= 1.6 Hz, 1 H), 5.10 (d, J = 4.4 Hz, 1 H), 4.99 (d, J = 3.2 Hz, 1 H), 4.61 - 4.52 (m, 3 H), 4.50 - 4.41 (m, 1 H), 4.38 - 4.32 (m, 2 H), 4.31 - 4.22 (m, 4 H), 4.11 (t, J= 8.0 Hz, 1 H), 4.05 - 3.90 (m, 2 H), 3.85 - 3.76 (m, 2 H), 3.73 - 3.67 (m, 1 H), 3.55 (d, J= 5.2, 10.4 Hz, 1 H), 2.82 (dd, J= 3.2, 15.2 Hz, 1 H), 2.77 - 2.70 (m, 1 H), 2.68 - 2.58 (m, 5 H), 2.53 - 2.40 (m, 2 H), 2.28 - 2.15 (m, 3 H), 2.11 - 1.91 (m, 4 H), 1.58 (d, J= 6.8 Hz, 2 H), 1.50 - 1.33 (m, 4 H), 1.33 - 1.25 (m, 11 H), 1.23 (d, J= 6.8 Hz, 2 H), 1.18 - 1.13 (m, 3 H), 1.07 (t, J = 7.2 Hz, 7 H), 0.96 - 0.89 (m, 2 H), 0.88 - 0.83 (m, 9 H). Example 40 (Compound S-118):

[0398] To a mixture of Example 41 Intermediate 1 (500 mg, 470 pmol, 1 eq) and NH4COOH (297 mg, 4.7 mmol, 10 eq) in MeOH (5 mL) was added NaBH3CN (30 mg, 470 pmol, 1 eq) in one portion at 25°C under N2atmosphere. The reaction mixture was heated to 50°C and stirred for 16 hours. After cooling to room temperature, the mixture was filtered and the filter cake was washed with MeOH (5 mL x 2), then filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75*30mm*3pm; mobile phase: [H2O(0.1%TFA)- ACN];gradient:30%-60% B over 8.0 min) to give Compound S-118 (105.4 mg, 99 pmol, 21% yield) as a white solid. MS (M+H): 1064.7 ; ’H NMR: MeOD 400 MHz: 5 ppm 0.85 - 0.88 (m, 8 H) 0.89 - 0.91 (m, 1 H) 0.92 - 0.96 (m, 1 H) 1.07 (br s, 1 H) 1.09 - 1.14 (m, 1 H) 1.17 (br d, .7=6.0 Hz, 3 H) 1.24 - 1.35 (m, 14 H) 1.42 (br dd, J=12.0, 5.2 Hz, 1 H) 1.46 - 1.51 (m, 1 H) 1.58 (br d, J=6.0 Hz, 2 H) 1.94 - 2.07 (m, 4 H) 2.22 (br t, J=7.2 Hz, 2 H) 2.25 - 2.32 (m, 1 H) 2.50 - 2.60 (m, 1 H) 2.79 - 2.92 (m, 1 H) 3.55 (br dd, J=11.2, 3.0 Hz, l H) 3.70 (br d, .7=10.4 Hz, 1 H) 3.78 - 3.86 (m, 1 H) 3.98 - 4.07 (m, 2 H) 4.24 (br d, .7=2,4 Hz, 2 H) 4.32 - 4.38 (m, 3 H) 4.43 - 4.48 (m, 2 H) 4.52 - 4.61 (m, 1 H) 4.64 (d, J=1.6 Hz, 1 H) 4.72 (dd, .7=3.6, 1.6 Hz, 1 H) 4.91 - 4.93 (m, 1 H) 5.12 - 5.17 (m, 1 H) 5.25 - 5.29 (m, 1 H) 6.77 - 6.86 (m, 2 H) 7.18 (d, J=8.8 Hz, 1 H) 7.41 (d, J=8.8 Hz, 2 H) 7.52 - 7.62 (m, 1 H) 8.22 (br d, .7=7,6 Hz, 1 H) 8.45 (br d, J=8.8 Hz, 1 H) 8.75 (br d, J=8.0 Hz, 1 H).

[0399] To a solution of pneumocandin bO (1.00 g, 939 umol, 1.00 eq) in Toluene (5 mL) and DMF (5 mL) was added MnO2(816 mg, 9.39 mmol, 10.0 eq) in one portion at 25°C under N2atmosphere. The system was degassed and then charged with nitrogen three times. The reaction mixture was heated and stirred at 110°C for 16 hours. After cooling to room temperature, water (70 mL) was added to the reaction mixture and extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with brine (20 mL x 2), dried over anhydrous Na2SO4;filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna 80 x 30mm x 3um; mobile phase: [water (TFA)-ACN]; B%: 40%-65%, 8 min) to give Intermediate 1 (338.4 mg, 318 umol, 33.9% yield)) as a white solid.

[0400] To a mixture of Intermediate 1 (180 mg, 169 pmol, 1 eq) and O-methylhydroxylamine; hydrochloride (14 mg, 169 pmol, 1 eq) in EtOH (2 mL) was added NaOAc (42 mg, 507 pmol, 3 eq) in one portion at 25°C under N2atmosphere. The reaction mixture was heated to 70°C and stirred for 4 hr. 50 mg batch was combined with the batch to work up. After cooling to room temperature, the combined mixture was filtered and the filtrate was concentrated under reduced to dryness. The residue was purified by prep-HPLC (neutral condition: column: Waters Xbridge Prep OBD C18 150*40mm*10um;mobile phase: [water( NH4HCO3)-ACN];B%: 45%-65%,8min) to give Compound S-119 (41.7 mg, 38.2 pmol, 18.5% yield) as a white solid. MS (M+H): 1092.5 ; H NMR: MeOD 400 MHz: 5 ppm 0.84 - 0.88 (m, 8 H) 0.89 - 0.90 (m, 1 H) 0.91 - 0.96 (m, 1 H) 1.04 - 1.09 (m, 1 H) 1.09 - 1.15 (m, 1 H) 1.19 - 1.26 (m, 5 H) 1.26 - 1.40 (m, 13 H) 1.45 (br s, 1 H) 1.46 - 1.53 (m, 1 H) 1.55 - 1.64 (m, 2 H) 1.72 - 1.82 (m, 1 H) 1.92 - 2.03 (m, 2 H) 2.04 - 2.12 (m, 1 H) 2.15 - 2.29 (m, 4 H) 2.48 - 2.58 (m, 1 H) 2.58 - 2.74 (m, 1 H) 3.76 - 3.78 (m, 3 H) 3.80 (br s, 1 H) 3.84 - 3.99 (m, 3 H) 4.23 - 4.31 (m, 1 H) 4.36 (br d, .7=2,0 Hz, 1 H) 4.41 - 4.52 (m, 4 H) 4.54 - 4.63 (m, 2 H) 4.94 - 5.04 (m, 2 H) 5.76 (d, .7=2,4 Hz, 1 H) 6.87 (d, J=8.8 Hz, 2 H) 7.33 (d, .7=6,4 Hz, 1 H) 7.88 - 7.99 (m, 2 H).

[0401] Example 42:

[0402] To a solution of Example 50 (200 mg, 169 pmol) in THF (2 mL) was added NaIO4(144 mg, 676 pmol) in H2O (0.5 mL) at 25°C. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was filtered through Buchner funnel and the filtrate was used to next step directly as a tetrahydrofuran (THF) solution.

[0403] To the above solution of Example 50 (-200 mg) in mixed THF and H2O (-2.2 mL) was added 2-(Diethylamino)ethanethiol (222 mg, 1.67 mmol) in one portion at 20°C. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was filtered and washed with THF (10 mL x 3), and the filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (column: Phenomenex Luna Ci875 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 min) to give Example 42 (19.2 mg, 14.7 pmol, 8.81% yield, TFA salt) as a white solid. MS (M+H): 1192.6 ; *H NMR: DMSO 400 MHz 5 = ppm 9.19 - 9.07 (m, 1H), 8.56 (d, J= 9.2 Hz, 1H), 8.50 - 8.41 (m, 1H), 8.23 (d, J= 8.8 Hz, 1H), 7.98 - 7.91 (m, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.43 (d, J= 9.8 Hz, 1H), 7.28 - 7.17 (m, 2H), 7.13 (d, J= 7.8 Hz, 2H), 6.71 (s, 1H), 5.41 - 5.33 (m, 1H), 5.23 (d, J= 9.6 Hz, 1H), 5.19 - 5.09 (m, 3H), 4.92 - 4.83 (m, 3H), 4.42 (s, 2H), 4.34-4.38 (m, 2H), 4.26 (d, J= 11.6 Hz, 1H), 4.20 - 4.10 (m, 4H), 4.02 - 3.88 (m, 2H), 3.83 (d, .7= 8.0 Hz, 1H), 3.71 (d, J= 10.8 Hz, 1H), 3.67 - 3.57 (m, 2H), 3.17 - 3.07 (m, 4H), 2.26 - 2.04 (m, 6H), 1.90 (d, J= 6.4 Hz, 2H), 1.52 - 1.41 (m, 4H), 1.33 - 1.15 (m, 24H), 1.11 - 0.96 (m, 6H), 0.92 - 0.87 (m, 1H), 0.85 - 0.80 (m, 10H)

[0404] Example 43:

[0405] To a solution of pneumocandin bO (1 g, 939 pmol) in DMF (100 mL) was added 2,4,6-trichloro-l,3,5-triazine (Cyanuric chloride, 402 mg, 2.18 mmol) in one portion at 10°C under N2atmosphere. The reaction mixture was stirred at 10°C for 10 minutes and then quenched with aqueous NaOAc (2 M, 50 mL) quickly. After stirring for further 5 minutes, the mixture was concentrated directly under reduced pressure to give a residue. The residue was suspended in H2O (100 mL). Then the solid was filtered and collected to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex luna Cl 8 250 x 50mm x 10 pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 40%-70% B over 10.0 minutes) to give Intermediate 1 (510 mg, 488 pmol, 51.9% yield) as a white solid.

[0406] To a solution of Intermediate 1 (400 mg, 382 pmol) in mixed solution of isopropanol (i-PrOH) (8.5 mL), H2O (1.5 mL) and AcOH (1 mL) were added ammonium acetate (1.00 g, 13.0 mmol) and Pd / C (200 mg, 10% purity) under N2atmosphere. The suspension was degassed and purged with H2for 3 times. The reaction mixture was stirred under H2(15 Psi) at 40°C for 28 hours. After cooling to room temperature, the mixture was filtered through a pad of celite and the filter cake was washed with i-PrOH (10 mL x 3). The filtrate was concentrated under reduced pressure to give yellow gum, which was purified by prep-HPLC (TFA condition): column: Phenomenex Luna C18 75 x 3 0mm x 3 pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 35%-65% B over 8.0 min) to give Intermediate 2 (122.8 mg, 117 pmol, 30.6% yield) as a white solid.

[0407] To a solution of Intermediate 2 (200 mg, 190 pmol) in MeOH (5 mL) were added NaBH(OAc)3 (403 mg, 1.90 mmol) and 4-Formylphenylboronic acid (114 mg, 761 pmol) in one portion at 25°C under N2atmosphere. The reaction mixture was stirred at 25 °C for 16 hours. NH4C1 aqueous (20 mL) was added to the above mixture and stirred for 10 minutes, then the mixture was extracted with ethylacetate (EtOAc) (20 ml x 2). The combined solution was dried over Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (TFA condition): column: Phenomenex luna C18 75 x 30mm x 3 pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-50% B over 8.0 min to give Example 43 (52.2 mg, 44.1 pmol, 23.2% yield) as a white solid. MS (M+H): 1185.5 ; ’H NMR: CD3OD 400 MHz 5 = ppm 9.07 (d, J= 8.4 Hz, 1H), 8.55 (d, J= 8.8 Hz, 1H), 8.33 (d, J= 8.4 Hz, 1H), 7.86 - 7.80 (m, 1H), 7.76 - 7.69 (m, 1H), 7.54 - 7.47 (m, 2H), 7.24 - 7.14 (m, 1H), 7.12 (d, J= 8.4 Hz, 2H), 6.75 (d, J= 8.4 Hz, 2H), 5.24 - 5.20 (m, 1H), 4.98 (dd, J= 2.8, 8.4 Hz, 1H), 4.66 - 4.53 (m, 4H), 4.37 - 4.33 (m, 1H), 4.30 - 4.27 (m, 3H), 4.23 - 4.20 (m, 2H), 4.07 - 3.93 (m, 3H), 3.89 - 3.79 (m, 4H), 2.66 (s, 1H), 2.45 (dd, J= 7.6, 12.8 Hz, 1H), 2.30 - 2.24 (m, 2H), 2.19 - 1.93 (m, 8H), 1.64 (d, J= 6.8 Hz, 1H), 1.50 - 1.45 (m, 2H), 1.44 - 1.28 (m, 9H), 1.25 (br s, 6H), 1.18 (d, J= 6.0 Hz, 2H), 1.13 - 1.03 (m, 3H), 0.96 - 0.89 (m, 2H), 0.87 - 0.84 (m, 9H). Example 44:

[0408] To a solution of Example 43 Intermediate 2 (0.4 g, 380 pmol) in MeOH (4 mL) were added NaBH(OAc)3(1.61 g, 7.61 mmol) and (3-formylphenyl)boronic acid (228 mg, 1.52 mmol) in one portion at 25°C, the mixture was degassed and purged with N2for 3 times. The reaction mixture was stirred at 25°C for 12 hours under N2atmosphere. NH4C1 aqueous (20 mL) was added to the result mixture and stirred for 10 minutes, then the mixture was extracted with EtOAc (20 ml x 2). The combined solution was dried over Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD C18 150x40mmxl0um;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:35%-65% B over 8.0 min) to give Example 44 (47.2 mg, 39.3 pmol, 10.3% yield, 98.7% purity) as a white solid. MS: (M+H):l 185.4 ; ’H NMR: DMSO 400 MHz 5 = ppm 7.70 - 7.60 (m, 1H), 7.49 (s, 1H), 7.32 - 7.19 (m, 1H), 7.12 (s, 1H), 7.06 (d, J= 8.4 Hz, 2H), 6.69 (d, J= 8.4 Hz, 2H), 4.95 (s, 1H), 4.77 (s, 1H), 4.59 - 4.41 (m, 3H), 4.38 - 4.21 (m, 4H), 4.18 - 4.10 (m, 2H), 4.08 - 3.89 (m, 5H), 3.70 - 3.45 (m, 6H), 3.07 (s, 2H), 2.76 - 2.63 (m, 1H), 2.36 - 2.24 (m, 1H), 2.21 - 2.10 (m, 2H), 2.07 - 1.99 (m, 2H), 1.97 - 1.73 (m, 6H), 1.35 (d, J= 6.4 Hz, 6H), 1.28 - 1.10 (m, 17H), 1.09 - 0.88 (m, 9H), 0.86 - 0.66 (m, 14H)

[0409] Example 45:

[0410] To a solution of Example 43 Intermediate 2 (400 mg, 380 pmol) and 2-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)benzaldehyde (353 mg, 1.52 mmol) in MeOH (4 mL) was added NaBH(OAc)3(1.61 g, 7.61 mmol, 20 eq) in one portion at 25°C, the mixture was degassed and purged with N2for 3 times. The reaction mixture was stirred at 25°C for 12 hours under N2atmosphere. NH4C1 aqueous (20 mL) was added to the above mixture and stirred for 10 minutes, then the mixture was extracted with EtOAc (20 ml x 2). The combined solution was dried over Na2SO4, filtered and concentrated under reduced pressure to give yellow gum, which was purified by prep-HPLC (column: Phenomenex luna Cl 8 250x50mmxl0 um;mobile phase: [H2O(0.1% TFA)-ACN];gradient:30%-70% B over 10.0 minutes) to give Example 45 (33 mg, 25.6 pmol, 6.74% yield, 98.5% purity) as a white solid. MS: (M+H): 1149.5 ;1H NMR: DMSO 400 MHz 5 = ppm 9.71 - 9.59 (m, 1H), 8.76 - 8.54 (m, 1H), 8.49 - 8.30 (m, 1H), 8.26 - 8.18 (m, 1H), 8.02 - 7.81 (m, 2H), 7.62 - 7.56 (m, 1H), 7.51 - 7.44 (m, 1H), 7.13 (d, J= 8.4 Hz, 2H), 6.84 (d, J= 8.4 Hz, 1H), 6.66 (d, J= 8.8 Hz, 1H), 6.05 - 5.92 (m, 1H), 5.63 - 5.44 (m, 1H), 5.15 - 4.95 (m, 2H), 4.92 - 4.71 (m, 4H), 4.68 - 4.59 (m, 1H), 4.54 - 4.41 (m, 2H), 4.38 - 4.28 (m, 2H), 4.27 - 3.93 (m, 7H), 3.86 (dd, J= 4.4, 9.2 Hz, 2H), 3.79 - 3.62 (m, 5H), 3.07 - 2.78 (m, 2H), 2.35 - 2.23 (m, 1H), 2.19 - 2.03 (m, 3H), 2.01 - 1.63 (m, 6H), 1.53 - 1.34 (m, 5H), 1.31 - 1.12 (m, 14H), 1.10 - 0.96 (m, 3H), 0.95 - 0.86 (m, 3H), 0.86 - 0.76 (m, 10H)

[0411] Example 46:

[0412] To a mixture of Example 50 (300 mg, 253 pmol) and Diethylethanolamine (3.00 mL) in THF (3 mL) and H2O (0.6 mL) was added NaIO4(216 mg, 1.01 mmol) at 20°C. The reaction mixture was heated to 50°C and stirred at 50°C for 6 hours. After cooling to room temperature, the reaction mixture was filtered and the filtrate was diluted with more H2O (5 mL), and then extracted with ethyl acetate (10 mL x 3). The combined organic layers were washed with brine (5 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Waters Xbridge Prep OBD Ci8150 x 40mm x lOum; mobile phase: [H2O (lOmM NH4HCO3)-ACN]; gradient: 35%-65% B over 8.0 min) to give Example 46 (45.2 mg, 38.4 pmol, 15.0% yield) as a white solid. MS: (M-Et2NCH2CH2OH+H): 1059.5 ;1H NMR: DMSO 400 MHz 5 = ppm 8.36 - 8.13 (m, 1H), 7.96 - 7.90 (m, 2H), 7.67 (d, J= 7.6 Hz, 2H), 7.53 - 7.43 (m, 1H), 7.23 - 7.15 (m, 3H), 7.13 - 7.07 (m, 1H), 6.91 - 6.85 (m, 1H), 6.12 - 5.86 (m, 1H), 5.25 (d, J= 4.0 Hz, 1H), 5.22 - 5.09 (m, 4H), 4.72 - 4.59 (m, 2H), 4.56 - 4.47 (m, 2H), 4.45 - 4.35 (m, 2H), 4.33 - 4.26 (m, 1H), 4.24 - 4.10 (m, 4H), 3.97 (d, J= 2.8 Hz, 1H), 3.92 - 3.81 (m, 2H), 3.79 - 3.72 (m, 1H), 3.70 - 3.58 (m, 2H), 2.85 - 2.75 (m, 1H), 2.72 - 2.65 (m, 1H), 2.40 - 2.32 (m, 3H), 2.23 - 2.12 (m, 3H), 2.03 - 1.90 (m, 3H), 1.84 - 1.77 (m, 1H), 1.56 - 1.38 (m, 5H), 1.35 - 1.12 (m, 20H), 1.11 - 1.00 (m, 3H), 0.92 - 0.80 (m, 12H)

[0413] Example 47:

[0414] A mixture of Example 50 (0.2 g, 169 pmol) in A,A-Dimethylethylenediamine (2.5 mL, 22.9 mmol) was stirred at 25°C for 16 hours. The mixture was quenched with water (10 mL), and then the mixture was adjusted pH=8 with 4N aqueous HC1, solid was precipitated, and the solid was collected by filtration and purified by prep-HPLC (column: Phenomenex Luna Ci875 x 30 mm x 3 um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 25%-50% B over 8.0 minutes) to give Example 47 (57.5 mg, 50.1 pmol, 29.6% yield, 100% purity, TFA salt) as a white solid. MS (M+H+): 1147.6 ; ’H NMR: DMSO 400 MHz5 ppm 8.56 (s, 1H), 8.24 (s, 1H), 7.95 (s, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.44 (d, J= 10.0 Hz, 1H), 7.25-7.23 (m, 2H), 7.13 (d, J= 8.0 Hz, 2H), 6.71 (s, 1H), 5.38 (s, 1H), 5.19-5.13 (m, 1H), 5.06 (s, 1H), 4.94-4.84 (m, 4H), 4.67-4.57 (m, 1H), 4.42 (s, 2H), 4.34 (dd, J= 11.2 Hz, 7.2 Hz, 1H), 4.26- 4.13 (m, 6H), 3.98 (br s, 2H), 3.83-3.81 (m, 1H), 3.72-3.70 (m, 1H), 3.64-3.60 (m, 2H), 3.19 (br s, 2H), 2.76 (s, 6H), 2.60-2.55 (m, 2H), 2.26-2.17 (m, 2H), 2.13-2.05 (m, 4H), 1.92-1.85 (m, 3H), 1.46-1.37 (m, 4H), 1.27-1.18 (m, 12H), 1.02-0.99 (m, 3H), 0.85-0.81 (m, 10H).

[0415] Example 48A and 48B:

[0416] A mixture of Example 50 (180 mg, 142 pmol) and N',N'-dimethylpropane-l,3- diamine (6.00 mL, 4.90 g, 48.0 mmol) was stirred at 25°C for 16 hours under N2 atmosphere. The mixture was quenched with water (10 mL), and then the mixture was adjusted pH=8 with aq. HC1 (4 N), yellow solid was precipitated, and the solid was collected by filtration and purified by prep-HPLC (column: Phenomenex Luna C18 75 x 30 mm x 3 um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 25%-50% B over 8.0 min) to give Example 48A (21.3 mg, 18.28 pmol, 99.66% purity) as a white solid. MS (M+H+): 1161.7 ; ’H NMR: DMSO 400 MHzS ppm 9.28 (s, 1H), 8.38-8.23 (m, 3H), 7.43-7.38 (m, 2H), 7.18-7.13 (m, 3H), 7.08- 7.04 (m, 1H), 7.00 (d, J= 8.4 Hz, 2H), 6.69-6.65 (m, 2H), 5.39 (br d, J= 10.4 Hz, 1H), 5.16- 5.08 (m, 4H), 5.01 (d, J= 5.6 Hz, 1H), 4.90-4.78 (m, 4H), 4.41-4.27 (m, 3H), 4.15-4.13 (m, 2H), 4.09-4.03 (m, 3H), 3.98-3.92 (m, 2H), 3.76-3.69 (m, 2H), 3.48-3.41 (m, 1H), 2.36 (s, 3H), 2.25-2.20 (m, 1H), 2.16-2.10 (m, 1H), 2.04 (t, J= 7.2 Hz, 2H), 1.90-1.81 (m, 2H), 1.70 (br s, 2H), 1.45-1.36 (m, 4H), 1.25-1.17 (m, 12H), 1.08-0.99 (m, 2H), 0.97-0.95 (m, 2H), 0.91-0.80 (m, 10H). This also gave Example 48B (21.5 mg, 18.73 pmol, 98.7% purity) as a white solid. MS (M+H+): 1133.7. ’H NMR: DMSO 400 MHz 5 ppm 9.55-9.42 (m, 1H), 9.15 (s, 1H), 9.00-8.93 (m, 1H), 8.86-8.71 (m, 1H), 8.73-8.61 (m, 1H), 8.38-8.25 (m, 1H), 7.94 (s, 1H), 7.68 (d, J= 8.0 Hz, 1H), 7.43-7.35 (m, 1H), 7.24-7.13 (m, 2H), 6.94 (d, J= 8.4 Hz, 2H), 6.71 (br s, 1H), 6.64 (d, J= 8.4 Hz, 2H), 5.54-5.51 (m, 1H), 5.44-5.41 (m, 1H), 5.16 (br s, 1H), 5.12-4.97 (m, 2H), 4.93-4.78 (m, 4H), 4.42 (br s, 2H), 4.38-3.98 (m, 10H), 3.84- 3.62 (m, 3H), 3.11-3.01 (m, 2H), 2.76 (br s, 6H), 2.26-2.16 (m, 2H), 2.14-2.06 (m, 4H), 1.96- 1.84 (m, 4H), 1.49-1.39 (m, 4H), 1.28-1.16 (m, 14H), 0.99 (br d, J= 6.0 Hz, 3H), 0.85-0.80 (m, 10H). Example 49:

[0417] A mixture of Example 50 (200 mg, 158 pmol) and 2-aminoethanol (5.06 g, 82.8 mmol, 5 mL) was stirred at 25°C for 2 hours under N2atmosphere. The reaction was quenched by addition of water (10 mL) at 25°C, then the mixture was adjusted to pH= 4 with IN aqueous HC1, yellow solid was precipitated and the solid was collected by filtration. The solid was purified by prep-HPLC (column: Waters Xbridge BEH C18 100 * 30 mm * 10 pm; mobile phase: [H2O (10 mM NH4HCO3)-ACN]; gradient: 10%-50% B over 8.0 min) to give crude product, which was further purified by prep-HPLC (column: Phenomenex Luna C18 75 * 30 mm * 3 um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 35%-55% B over 8.0 min) to give pure Example 49 (61.7 mg, 54.79 pmol, 61.4% yield, 99.5% purity) as a white solid. MS [M+H]+: 1120.6 ; ’H NMR: DMSO-t / 6400 MHz 5 ppm 8.84-8.82 (m, 2H), 8.69-8.62 (m, 1H), 8.473-8.35 (m, 1H), 8.32 (d, J= 8.4 Hz, 1H), 7.94 (s, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.44-7.44 (m, 1H), 7.30-7.18 (m, 2H), 7.13 (d, J= 7.6 Hz, 2H), 6.71 (s, 1H), 5.44-5.36 (m, 2H), 5.16 (s, 1H), 5.12-5.04 (m, 2H), 5.00-4.80 (m, 5H), 4.46-4.39 (m, 2H), 4.37-4.00 (m, 10H), 3.85-3.77 (m, 1H), 3.71 (d, J= 10.8 Hz, 1H), 3.67-3.64 (m, 3H), 2.94-2.79 (m, 2H), 2.29-1.81 (m, 9H), 1.51-1.34 (m, 5H), 1.34-1.13 (m, 15H), 1.10-0.95 (m, 5H), 0.93-0.86 (m, 1H), 0.84-0.81 (m, 10H).

[0418] Example 50:

[0419] A mixture of pneumocandin bO (10.0 g, 9.39 mmol), 2-methylbenzenethiol (1.17 g, 9.39 mmol, 1.11 mL) and phenylboronic acid (1.80 g, 14.8 mmol) in MeCN (150 mL) was cooled to -30°C, then triflic acid TfOH (4.23 g, 28.2 mmol, 2.49 mL) was added drop-wise at -30°C. After addition, the reaction mixture was warmed and stirred at -20°C for 4 hours. The reaction mixture was poured onto ice-water (100 mL), and some white solid was precipitated. The mixture was filtered and the filter cake was washed with water (20 mL x 3), and the solid was collected and dried in vacuo to give Intermediate 1 (10.6 g, crude) as a white solid.

[0420] To a solution of Intermediate 1 (20 g, 17.1 mmol) in TFA (300 mL) was added triethylsilane (Et3SiH) (19.9 g, 171 mmol, 27.3 mL) carefully at 0°C. The reaction mixture was stirred at 0°C for 1 hour. The mixture was poured onto ice-water (500 mL), white solid was precipitated. The mixture was filtered and the filter cake was washed with water (50 mL x 3), and the solid was collected and dried in vacuo to give Intermediate 2 (18.0 g, crude) as a white solid.

[0421] To a solution of Intermediate 2 (18.0 g, 15.6 mmol) in DMF (50 mL) and THF (150 mL) were added Cs2CO3(10.2 g, 31.2 mmol) and then PhNTf2(8.35 g, 23.4 mmol) at -10°C. The reaction mixture was warmed to 20°C and stirred at 20°C for 3 hours. The reaction mixture was quenched by addition of water (100 mL) at 0°C, and then extracted with EtOAc (100 mL x 3). The combined organic solution was washed with brine (200 mL x 2), dried over Na2SO4, filtered and concentrated under reduced pressure to dress to give yellow gum, which was purified by prep-HPLC (column: Welch Xtimate Cl 8 250 x 100 mm x 10 pm; mobile phase: [H2O (lOmM NH4HCO3)-THF]; gradient:35%-70% B over 20.0 minutes). The eluent was lyophilized through lyophilizer to give Intermediate 3 (13.0 g, 64.8% yield) as a white solid.

[0422] A suspension of Intermediate 3 (1.5 g, 1.17 mmol), B2Pin2(880 mg, 3.50 mmol), potassium acetate (KOAc) (230 mg, 2.33 mmol) and Xphos-Pd-G2 (458 mg, 582 pmol) in dry 1,4-di oxane (25 mL) was degassed and purged with N2for 3 times, and then the reaction mixture was heated to 80°C and stirred at 80°C for 2 hour under N2atmosphere. After cooling, the mixture was filtered through a pad of Celite and the filter cake was washed with EtOAc (30 mL x 3). The filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (column: Phenomenex luna Cl 8 100 x 40 mm x 5 um; mobile phase: [H2O (0.2% FA)-ACN]; gradient: 45%-85% B over 8.0 min). The eluent was lyophilized through lyophilizer to give crude Example 50 (370 mg, -85% purity). MS [M+H]+: 1183.6. ; Hl NMR: DMSO-t / 6400 MHz 5 ppm 8.40-8.24 (m, 3H), 7.95 (s, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.48-7.43 (m, 2H), 7.21-7.05 (m, 7H), 6.71 (br.s, 1H), 5.41 (d, J= 10.0 Hz, 1H), 5.17-5.02 (m, 5H), 4.87-4.80 (m, 3H), 4.43- 4.10 (m, 9H), 3.97-3.94 (m, 1H), 3.82- 3.70 (m, 3H), 3.49-3.44 (m, 1H), 2.37 (s, 3H), 2.28-2.20 (m, 1H), 2.15-2.02 (m, 3H), 1.97- 1.81 (m, 3H), 1.75-1.67 (m, 2H), 1.48-1.13 (m, 20H), 1.09-0.96 (m, 5H), 0.92-0.86 (m, 1H), 0.86-0.80 (m, 10H).

[0423] Example 51:

[0424] To a solution of Example 58 (5 g, 421 pmol) in MeOH (4.5 mL) was added 3- phenylpropan-1 -amine (31.6 mmol, 4.5 mL) in one portion at 25°C, the reaction mixture was degassed and purged with N2for 3 times and stirred for 12 hours under N2atmosphere. The crude solution was purified directly by prep-HPLC (column: 3_Phenomenex Luna Cl 8 75x30mmx3um;mobile phase: [H2O(0.1%TFA)-ACN];gradient:35%-65% B over 8.0 minutes). The residue was purified by prep-HPLC (column: Phenomenex Luna Cl 8 75x30mmx3um;mobile phase: [H2O(0.1% TFA)-ACN];gradient:35%-65% B over 8.0 min) to give Example 51 (20.3 mg, 15.8 pmol, 3.76% yield, 94.5% purity) as a white solid. MS: (M+H): 1210.8 ; ’H NMR: DMSO Bruker_W_400MHz 5 = ppm 8.60 - 8.59 (m, 1H), 8.57 - 8.33 (m, 1H), 7.70 - 7.68 (m, 2H), 7.44 - 7.42 (m, 1H), 7.29 - 7.25 (m, 3H), 7.19 - 7.16 (m, 5H), 4.90 - 4.88 (m, 23H), 4.41 - 4.40 (m, 2H), 4.14 - 4.11 (m, 8H), 4.05 - 4.00 (m, 2H), 2.73 - 2.71 (m, 3H), 2.20 - 2.05 (m, 2H), 2.05 - 2.04 (m, 3H), 2.04 - 1.87 (m, 12H), 1.41 - 1.39 (m, 5H), 1.17 - 1.16 (m, 18H), 0.97 - 0.95 (m, 6H), 0.82 - 0.78 (m, 13H)

[0425] Example 52:

[0426] To a solution of Example 58 (350 mg, 295 pmol) in MeOH (3 mL) was added N,N- Dimethyl-l,4-butanediamine (0.86g, 7.3 mmol) in one portion at 25°C. Then mixture was stirred for 16 hours at 25°C. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient:30%-50% B over 8.0 minutes) to give Example 52 (18.5 mg, 14.17 pmol, 17.14% yield, TFA salt) as a white solid. MS (M+H): 1191.7 ; ’H NMR: MeOD 400MHz 5 = ppm 8.82 - 8.80 (m, 1H), 7.61 - 7.59 (m, 1H), 7.49 - 7.44 (m, 1H), 7.35 - 7.31 (m, 1H), 5.43 (s, 1H), 5.08 - 5.03 (m, 2H), 4.85 - 4.84 (m, 6H), 4.40 - 4.28 (m, 5H), 3.96 - 3.75 (m, 4H), 3.19 - 3.18 (m, 2H), 2.91 (s, 6H), 2.75 - 2.72 (m, 1H), 2.50 - 2.01 (m, 10H), 1.83 - 1.82 (m, 5H), 1.70 - 1.52 (m, 3H), 1.49 - 1.12 (m, 20H), 0.90 - 0.85 (m, 12H).

[0427] Example 53:

[0428] To a solution of Example 58 (350 mg, 295 pmol) in MeOH (3 mL) was added benzylamine (2.35 g, 21.9 mmol) in one portion at 25°C. Then mixture was stirred for 16 hours at 25°C. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (HC1 condition: column: Phenomenex Luna C18 100 x 30mm x 3um; mobile phase: [H2O (0.04% HC1)-ACN]; gradient: 15%-45% B over 8.0 min) to give Example 53 (21.3 mg, 17.4 pmol, 5.92% yield, HC1 salt) as a white solid. MS (M+H): 1182.6 ; ’H NMR: MeOD 400MHz 5 = ppm 9.11 - 9.08 (m, 1H), 9.02 - 8.82 (m, 1H), 8.16 - 7.99 (m, 1H), 7.88 - 7.69 (m, 1H), 7.68 - 7.62 (m, 1H), 7.62 - 7.56 (m, 1H), 7.54 - 7.44 (m, 3H), 7.43 - 7.31 (m, 1H), 7.16 (s, 1H), 5.46 - 5.38 (m, 1H), 5.27 - 5.10 (m, 1H), 5.09 - 5.01 (m, 1H), 4.97 (s, 1H), 4.69 - 4.56 (m, 2H), 4.54 - 4.36 (m, 4H), 4.35 - 4.26 (m, 2H), 4.23 (d, J= 7.6 Hz, 1H), 4.10 - 3.97 (m, 1H), 3.94 - 3.79 (m, 2H), 2.85-2.80 (m, 1H), 2.59 - 2.42 (m, 2H), 2.38 - 1.98 (m, 5H), 1.68 - 1.47 (m, 3H), 1.43 - 1.23 (m, 11H), 1.22 - 1.03 (m, 4H), 1.01 - 0.85 (m, 8H).

[0429] Example 54:

[0430] To a solution of Example 58 (500 mg, 422 pmol) in MeOH (5 mL) was added 2- amino-N,N-dimethyl-acetamide (302 mg, 2.95 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (HC1 condition: column: Phenom enex Luna Cl 8 100*30mm*3pm;mobile phase: [H20(0.04% HC1)- ACN];gradient: 15%-45% B over 8.0 minutes) to give Example 54 (28.2 mg, 23.9 pmol, 20.28% yield) as a white solid. MS (M+H): 1177.7 ; ’H NMR: MeOD 400 MHz 5 = ppm 9.07 - 8.91 (m, 2H), 8.19 (d, J= 9.2 Hz, 1H), 7.73 (t, J= 9.2 Hz, 1H), 7.60 (d, J= 8.0 Hz, 1H), 7.49 - 7.40 (m, 1H), 7.33 (d, J= 8.4 Hz, 1H), 7.13 (d, J = 8.4 Hz, 1H), 6.75 (d, J= 8.0 Hz, 1H), 5.33 - 5.27 (m, 1H), 5.19 - 5.06 (m, 2H), 5.05 - 4.96 (m, 1H), 4.65 - 4.48 (m, 3H), 4.48 - 4.38 (m, 2H), 4.36 - 4.20 (m, 4H), 4.04 - 3.97 (m, 1H), 3.94 (d, J= 6.4 Hz, 2H), 3.90 - 3.75 (m, 2H), 3.02 - 2.93 (m, 6H), 2.83 - 2.75 (m, 1H), 2.53 - 2.38 (m, 2H), 2.36 - 2.22 (m, 3H), 2.20 - 2.11 (m, 2H), 2.10 - 1.92 (m, 2H), 1.68 - 1.55 (m, 1H), 1.52 - 1.37 (m, 3H), 1.35 - 1.19 (m, 15H), 1.14 (d, J= 5.6 Hz, 3H), 1.11 (d, J= 6.8 Hz, 1H), 1.08 (d, J= 6.8 Hz, 1H), 0.97 - 0.92 (m, 1H), 0.90 (s, 1H), 0.86 (d, J= 6.4 Hz, 8H).

[0431] Example 55:

[0432] To a solution of Example 58 (500 mg, 422 pmol) in MeOH (5 mL) was added N',N'- dimethylpropane- 1,3 -diamine (3.12 g, 30.6 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The residue was purified by prep-HPLC (HC1 condition: column: Phenomenex Luna C18 100*30mm*3pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:5%-35% B over 8.0 min) to give Example 55 (31.5 mg, 26.8 pmol, 6.34% yield) as a white solid. MS (M+H): 1177.7 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.84-7.79 (m, 1H), 8.02 (d, J= 8.0 Hz, 1H), 7.93 - 7.87 (m, 1H), 7.71 (d, J= 8.0, 1H), 7.69- 7.59 (m, 2H), 7.49 - 7.32 (m, 2H), 5.49-4.58 (m, 4H), 4.42-4.30 (m, 9H), 4.00-3.81 (m, 3H), 3.31-2.95 (m, 5H), 2.95(d, J = 8.4 Hz, 6H), 2.45-2.30 (m, 11H), 1.71 (m, 3H), 1.55 - 1.21 (m, 17H), 1.21 - 1.02 (m, 7H), 1.00 - 0.81 (m, 8H).

[0433] Example 56:

[0434] To a solution of pneumocandin bO (500 mg, 469 pmol) in DMSO (1 mL) was added [(IS, 4R)-7, 7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (109 mg, 469 pmol) and 2-Bromobenzeneethanol (2.36 g, 11.7 mmol, 25 eq) in one portion at 25°C. The reaction was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: 3_Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 45%-75% B over 8.0 min) to give Intermediate 1 (170 mg, 136 pmol, 29.0% yield) as a white solid.

[0435] To a solution of Intermediate 1 (120 mg, 97.1 pmol) in DMA (2 mL) were added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (B2Pin2, 81.3 mg, 291 pmol), KO Ac (19.0 mg, 194 pmol) and [2-(2- aminophenyl)phenyl]palladium(l+);bis(l-adamantyl)-butyl-phosphane;methanesulfonate (Catacxium A-Pd-G3, 35.3 mg, 48.5 pmol) in one portion at 25°C under N2atmosphere. The system was degassed and purged with N2for 3 times. The reaction mixture was heated to 80°C and stirred for 1 hour under N2atmosphere. After cooling to room temperature, the mixture was filtered and the filter cake was washed with ethyl acetate (10 mL x 3), then filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (HC1 condition: column: Phenomenex luna C18 100 x 40mm x 5 um;mobile phase: [H20(0.04% HCl)-ACN];gradient:25%-65% B over 8.0 min) to afford pure Example 56 (16.1 mg, 12.4 pmol, 12.8% yield) as a white solid. MS (Fragment MS): 1177.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 7.76 - 7.17 (m, 10H), 6.76 - 6.74 (m, 2H), 5.10 - 4.98 (m, 4H), 4.85 - 4.56 (m, 4H), 4.55 - 4.34 (m, 7H), 4.28 - 3.80 (m, 4H), 3.78 - 3.55 (m, 4H), 2.92 - 2.75 (m, 3H), 2.59 - 2.46 (m, 3H), 2.24 - 2.20 (m, 3H), 2.02 - 1.96 (m, 4H), 1.68 - 1.18 (m, 27H), 0.89 - 0.85 (m, 10H). Example 57:

[0436] To a solution of Example 58 (500 mg, 421 pmol) in MeOH (4 mL) was added 2- phenylethanamine (3.83 g, 31 mmol) at 20°C. The reaction mixture was stirred at 20°C for 16 hours. The residue was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex Luna Ci875 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:35%-65% B over 8.0 minutes) to give crude product, which was further purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 um;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-55% B over 8.0 minutes) to give pure Example 57 (15.3 mg, 12.7 pmol, 3% yield, HC1 salt) as a white solid. MS (M+H): 1196.6 ; ’H NMR: DMSO 400 MHz 5 = ppm 8.58 (d, J= 8.0 Hz, 1H), 8.33 (d, J = 8.4 Hz, 1H), 7.69 (d, J= 8.0 Hz, 2H), 7.43 (d, J= 10.0 Hz, 1H), 7.34 - 7.27 (m, 2H), 7.27 - 7.16 (m, 5H), 5.02 (s, 1H), 4.89 - 4.87 (m, 1H), 4.81 - 4.79 (m, 1H), 4.42 (s, 2H), 4.23 - 4.15 (m, 5H), 4.15 - 4.08 (m, 2H), 4.08 - 3.99 (m, 2H), 3.68 - 3.57 (m, 2H), 2.96 - 2.93 (m, 5H), 2.27 - 1.93 (m, 6H), 1.91 - 1.78 (m, 2H), 1.46 - 1.30 (m, 5H), 1.30 - 1.08 (m, 14H), 1.07 - 0.91 (m, 6H), 0.80 - 0.76 (m, 10H).

[0437] Example 58:

[0438] To a solution of Example 77 (1.5 g, 1.37 mmol) in MeCN (50 mL) was added phenylboronic acid (334 mg, 2.74 mmol) in one portion at 25°C. Then benzenethiol (870 mg, 7.90 mmol,) was added dropwise to the reaction at -15 °C. The reaction mixture was stirred at -15°C for 0.5 hours. Then TfOH (617 mg, 4.12 mmol) was added to the reaction mixture. The resulting mixture was stirred at -15°C for 0.5 hours. Then the reaction mixture was warmed to 15°C and stirred for 3 hours. 10 mL of saturated aqueous sodium acetate solution was added to the reaction mixture and stirred for 10 min. Some white solid was precipitated and the solid was filtered and the filter cake was washed with MeCN (10 mL x 3). The solid was concentrated under reduced pressure to give a crude 17 (1.35 g, crude). 150 mg of the crude product was purified by prep-HPLC (FA condition: column: Phenomenex luna Cl 8 100 x 40mm x 3 pm;mobile phase: [H2O(0.2% FA)-ACN];gradient:60%-95% B over 8.0 minutes) to give pure Example 58 (31.2 mg, 26 pmol, 19.1% yield) as a white solid. MS (M+H): 1185.2 ; ’H NMR: DMSO 400MHz 5 = ppm 8.50 - 8.42 (m, 1H), 8.28 (d, J= 7.6 Hz, 2H), 7.84 - 7.75 (m, 1H), 7.73 - 7.64 (m, 1H), 7.39 (d, J = 7.6 Hz, 2H), 7.33 - 7.13 (m, 7H), 6.76 - 6.68 (m, 1H), 5.46 - 5.37 (m, 1H), 4.91 - 4.73 (m, 2H), 4.69 - 4.55 (m, 1H), 4.54 - 4.38 (m, 1H), 4.36 - 4.23 (m, 2H), 4.20 - 3.98 (m, 6H), 3.97 - 3.88 (m, 1H), 3.79 - 3.62 (m, 3H), 2.27 - 2.12 (m, 2H), 2.09 - 1.95 (m, 2H), 1.93 - 1.84 (m, 1H), 1.83 - 1.68 (m, 3H), 1.50 - 1.32 (m, 5H), 1.31 - 1.10 (m, 16H), 1.07 - 0.98 (m, 2H), 0.95 (d, J = 6.0 Hz, 1H), 0.91 - 0.88 (m, 1H), 0.86-0.85 (m, 1H), 0.79 (d, J = 6.8 Hz, 8H).

[0439] Example 59:

[0440] To a mixture of pneumocandin bO (500 mg, 469 pmol) and (2- bromophenyl)methanol ( 2.19 g, 11.7 mmol) in DMSO (5 mL) was added [(lS,4R)-7,7- dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex luna Cl 8 100 x 40mm x 3 pm;mobile phase: [H2O(0.1%TFA)-ACN];gradient:45%-75% B over 8.0 minutes) to Intermediate 1 (160 mg, 130 pmol, 27.1% yield) as a white solid.

[0441] To a mixture of Intermediate 1 (160 mg, 129 pmol) and 4,4,5,5-tetramethyl-2- (4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (B2pin2, 65.8 mg, 259 pmol) in DMA (2 mL) were added KO Ac (25.4 mg, 259 pmol) and [2-(2- aminophenyl)phenyl]palladium(l+) ;bis(l-adamantyl)-butyl-phosphane;methanesulfonate (Catacxium A-Pd-G3, 47.1 mg, 64.8 pmol) in one portion at 25°C under N2atmosphere. The system was degassed and purged with N2for 3 times. The reaction mixture was heated to 80°C and stirred for 0.5 hour. After cooling to room temperature, the mixture was filtered and the filter cake was washed with ethyl acetate (5 mL x 3), then the filtrate was concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:50%-80% B over 8.0 min) to give Example 59 (16.3 mg, 10.9 pmol, 10.4% yield, 94.9% purity) as a white solid. MS (fragment MS): 1181.6 ;XH NMR: MeOD 400 MHz 5 ppm 0.83 - 0.88 (m, 8 H) 0.89 - 0.91 (m, 1 H) 0.92 - 0.97 (m, 1 H) 1.03 - 1.09 (m, 1 H) 1.12 (br d, J=6.0 Hz, 1 H) 1.17 (br d, J=6.0 Hz, 2 H) 1.21 - 1.37 (m, 15 H) 1.39 - 1.44 (m, 1 H) 1.44 - 1.52 (m, 2 H) 1.55 - 1.62 (m, 1 H) 2.01 (br s, 1 H) 2.02 - 2.10 (m, 3 H) 2.21 (br t, J=7.6 Hz, 1 H) 2.27 - 2.35 (m, 1 H) 2.43 (br dd, J=13.2, 7.6 Hz, 1 H) 2.52 (td, J=10.4, 4.8 Hz, 1 H) 2.83 (dd, J=15.6, 3.2 Hz, 1 H) 3.76 - 3.87 (m, 2 H) 3.92 - 3.99 (m, 1 H) 4.02 - 4.08 (m, 1 H) 4.18 - 4.25 (m, 1 H) 4.25 - 4.30 (m, 2 H) 4.31 - 4.39 (m, 4 H) 4.41 - 4.53 (m, 2 H) 4.54 - 4.61 (m, 3 H) 4.61 - 4.68 (m, 1 H) 4.68 - 4.74 (m, 1 H) 5.00 (br dd, J=8.8, 3.2 Hz, 1 H) 5.08 - 5.14 (m, 1 H) 5.22 - 5.35 (m, 1 H) 6.72 - 6.78 (m, 2 H) 7.06 (d, J=7.6 Hz, 1 H) 7.14 (dd, J=8.8, 2.0 Hz, 2 H) 7.22 - 7.26 (m, 1 H) 7.27 - 7.35 (m, 2 H) 7.40 - 7.47 (m, 1 H) 7.51 (br d, J=8.4 Hz, 1 H) 7.76 (br dd, J=12.8, 9.6 Hz, 1 H) 8.46 (br d, J=9.6 Hz, 1 H) 8.75 (br d, J=8.8 Hz, 1 H) 8.87 - 9.02 (m, 1 H).

[0442] Example 60:

[0443] To a mixture of Example 79 (350 mg, 292 pmol) and 2-aminoethanol;hydrochloride (2.85 g, 29.2 mmol) in DMSO (5 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l- yl]methanesulfonic acid (67.8 mg, 292 pmol) in one portion at 25°C. The reaction mixture was stirred at 25 °C for 16 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75x30mmx3pm;mobile phase: [H2O(0.1% TFA)- ACN];gradient:30%-60% B over 8.0 minutes) to give a crude product. The crude product was further purified by prep-HPLC (HC1 condition: column: Phenomenex luna C18 100x40mmx5 pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 minutes) to give pure Example 60 (38.5 mg, 30.9 pmol, 10.62% yield) as a white solid. MS (M+H): 1242.6 ; ’H NMR: MeOH400 MHz 5 ppm 0.85 (d, J=6.4 Hz, 8 H) 0.89 - 0.90 (m, 1 H) 0.91 - 0.96 (m, 1 H) 1.05 - 1.08 (m, 1 H) 1.09 - 1.14 (m, 1 H) 1.27 - 1.34 (m, 16 H) 1.40 - 1.44 (m, 1 H) 1.50 (br dd, J=6.4, 2.4 Hz, 1 H) 1.58 - 1.67 (m, 2 H) 1.94 - 2.01 (m, 1 H) 2.07 (td, J=9.2, 4.8 Hz, 1 H) 2.15 (br dd, J=8.4, 4.0 Hz, 1 H) 2.18 - 2.25 (m, 1 H) 2.34 - 2.40 (m, 2 H) 2.42 - 2.49 (m, 2 H) 2.51 - 2.63 (m, 2 H) 3.05 (td, J=8.4, 4.0 Hz, 1 H) 3.15 - 3.23 (m, 2 H) 3.81 - 3.86 (m, 3 H) 3.87 - 3.94 (m, 2 H) 3.95 - 4.04 (m, 1 H) 4.15 - 4.18 (m, 1 H) 4.24 (dd, J=14.8, 2.4 Hz, 1 H) 4.33 (br dd, J=4.4, 3.6 Hz, 3 H) 4.46 (br dd, J=8.6, 4.3 Hz, 1 H) 4.51 (br s, 1 H) 4.58 (br dd, J=6.8, 2.9 Hz, 1 H) 4.62 - 4.66 (m, 1 H) 4.71 (br t, J=8.8 Hz, 1 H) 4.76 - 4.79 (m, 1 H) 5.08 - 5.12 (m, 2 H) 5.17 - 5.24 (m, 1 H) 5.44 (s, 1 H) 6.93 - 6.98 (m, 2 H) 7.31 (br dd, J=8.4, 4.8 Hz, 2 H) 7.43 (br d, J=8.0 Hz, 2 H) 7.63 (d, J=8.0 Hz, 2 H).

[0444] Example 61:

[0445] To a solution of pneumocandin bO (700 mg, 657 pmol) in DMSO (7 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norboman-l-yl] methanesulfonic acid (152 mg, 657 pmol) and 4-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)benzeneethanol (1.63 g, 6.57 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure. The residue was purified by prep-HPLC (HC1 condition: column: Phenomenex luna C18 100 x 40mm x 5 pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 minutes] ;gradi ent: 35%-65% B over 8.0 min) to give Example 61 (31.3 mg, 25.8 pmol, 3.93% yield) as a white solid. MS (M+H): 1213.2 ; ’H NMR: MeOD 400 MHz 5 ppm 0.8 (dd, J=6.4, 3.6 Hz, 8 H) 0.9 (s, 1 H) 0.9 (br d, J=6.8 Hz, 1 H) 1.0 (br d, J=6.0 Hz, 1 H) 1.0 - 1.1 (m, 2 H) 1.1 (br d, J=6.0 Hz, 1 H) 1.2 (br d, J=6.4 Hz, 2 H) 1.2 - 1.2 (m, 3 H) 1.3 (br s, 13 H) 1.3 (br s, 1 H) 1.4 - 1.4 (m, 2 H) 1.5 (br d, J=2.4 Hz, 1 H) 1.5 - 1.6 (m, 2 H) 2.0 - 2.0 (m, 3 H) 2.1 (br d, J=3.2 Hz, 1 H) 2.2 - 2.2 (m, 3 H) 2.4 -

[0446] 2.5 (m, 1 H) 2.5 - 2.5 (m, 1 H) 2.8 (br s, 1 H) 2.9 - 2.9 (m, 1 H) 2.9 - 3.0 (m, 1 H) 3.4 - 3.5 (m, 1 H) 3.7 - 3.7 (m, 1 H) 3.8 (br d, J=9.6 Hz, 3 H) 3.9 - 4.1 (m, 3 H) 4.3 (s, 4 H) 4.3 (br s, 1 H) 4.3 - 4.4 (m, 1 H) 4.6 (br d, J=5.2 Hz, 2 H) 5.0 (br d, J=3.6 Hz, 1 H) 5.1 (br dd, J=8.4, 3.6 Hz, 2 H) 5.2 - 5.2 (m, 1 H) 6.8 (d, J=8.4 Hz, 2 H) 6.8 - 6.8 (m, 1 H) 7.1 (br d, J=8.4 Hz, 2 H)

[0447] 7.2 (br d, J=2.4 Hz, 1 H) 7.2 (br d, J=7.2 Hz, 2 H) 7.3 - 7.4 (m, 1 H) 7.5 - 7.5 (m, 1 H) 7.5 -

[0448] 7.6 (m, 2 H) 7.9 - 7.9 (m, 1 H) 8.3 (br d, J=9.6 Hz, 1 H) 8.7 (s, 1 H)

[0449] Example 62:

[0450] To a solution of pneumocandin bO (700 mg, 657 pmol) in DMSO (7 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norboman-l-yl] methanesulfonic acid (152 mg, 657 pmol) and 3-(4,4,5,5-Tetramethyl-l,3,2-dioxaborolan-2-yl)benzeneethanol (1.63 g, 6.57 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (HC1 condition: column: Phenomenex luna C18 100 x 40mm x 5 pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:35%-65% B over 8.0 minutes) to give Example 62 (40 mg, 32 pmol, 5.0% yield) as a white solid. MS (M+H): 1213.2 ; ’H NMR: MeOD 400 MHz 5 ppm 0.8 - 0.9 (m, 8 H) 0.9 (s, 1 H) 0.9 (br s, 1 H) 1.1 (td, J=12.8, 7.2 Hz, 3 H) 1.2 (br d, J=6.4 Hz, 2 H) 1.2 - 1.2 (m, 4 H) 1.3 (br d, J=6.4 Hz, 11 H) 1.3 (br s, 1 H) 1.4 - 1.4 (m, 1 H) 1.4 (br dd, J=12.4, 6.8 Hz, 2 H) 1.5 - 1.6 (m, 2 H) 2.0 - 2.0 (m, 3 H) 2.1 - 2.1 (m, 1 H) 2.2 -

[0451] 2.2 (m, 3 H) 2.4 - 2.5 (m, 1 H) 2.5 - 2.5 (m, 1 H) 2.8 - 2.9 (m, 2 H) 2.9 - 3.0 (m, 2 H) 3.7 - 3.7 (m, 1 H) 3.7 - 3.8 (m, 3 H) 4.0 (br dd, J=10.8, 3.2 Hz, 1 H) 4.0 - 4.0 (m, 1 H) 4.1 (br d, J=9.2 Hz, 1 H) 4.3 (s, 3 H) 4.3 (br d, J=3.2 Hz, 1 H) 4.3 (br d, J=3.6 Hz, 1 H) 4.5 (br dd, J=11.6, 6.0 Hz, 1 H) 4.6 (br d, J=3.6 Hz, 2 H) 5.0 - 5.0 (m, 1 H) 5.1 (br dd, J=8.4, 4.0 Hz, 1 H) 5.2 - 5.2 (m, 1 H) 6.7 (d, J=8.4 Hz, 2 H) 6.8 - 6.8 (m, 1 H) 7.1 (d, J=8.4 Hz, 2 H) 7.2 (br s, 1 H) 7.3 (br s, 2 H) 7.5 (br d, J=12.4 Hz, 2 H) 7.5 (br d, J=8.4 Hz, 1 H) 7.7 - 7.8 (m, 1 H) 8.3 (br d, J=9.2 Hz, 1 H) 8.7 (br d, J=8.0 Hz, 1 H).

[0452] Example 63:

[0453] To a mixture of pneumocandin bO (700 mg, 657 pmol) and [4-(4,4,5,5-tetramethyl- l,3,2-dioxaborolan-2-yl)phenyl]methanol (2.31 g, 9.86 mmol) in DMSO (5 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (153 mg, 657 pmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: column: Phenomenex Luna C18 75 x 30mm x 3um;mobile phase: [H2O(0.1% TFA)-ACN];gradient:35%-65% B over 8.0 min) to give Example 63 (42.7 mg, 33.3 pmol, 5.07% yield) as a white solid. MS (M+H): 1199.6 ; ’H NMR: MeOD 400 MHz 5 ppm 0.85 (dd, J=6.4, 3.6 Hz, 8 H) 0.89 (s, 1 H) 0.90 - 0.95 (m, 1 H) 1.00 - 1.04 (m, 1 H) 1.10 (br d, J=6.4 Hz, 1 H) 1.15 (br d, J=6.0 Hz, 3 H) 1.21 - 1.31 (m, 16 H) 1.42 (br dd, J=12.8, 6.4 Hz, 2 H) 1.50 - 1.56 (m, 2 H) 1.97 (br dd, J=6.8, 3.6 Hz, 1 H) 2.00 - 2.06 (m, 2 H) 2.09 - 2.14 (m, 2 H) 2.18 - 2.23 (m, 1 H) 2.41 - 2.46 (m, 1 H) 2.48 - 2.55 (m, 1 H) 2.82 (br dd, J=15.6, 3.2 Hz, 1 H) 3.77 - 3.82 (m, 2 H) 3.95 (br d, J=8.4 Hz, 1 H) 4.02 (br t, J=8.0 Hz, 1 H) 4.11 - 4.19 (m, 2 H) 4.28 (s, 2 H) 4.29 (br s, 1 H) 4.32 (br d, J=3.2 Hz, 1 H) 4.35 - 4.38 (m, 1 H) 4.41 - 4.47 (m, 1 H) 4.55 - 4.58 (m, 2 H) 4.60 - 4.65 (m, 2 H) 4.97 (br dd, J=9.2, 3.2 Hz, 1 H) 5.08 - 5.12 (m, 1 H) 5.21 - 5.30 (m, 1 H) 6.75 (d, J=8.4 Hz, 2 H) 6.77 - 6.82 (m, 1 H) 7.08 - 7.20 (m, 3 H) 7.32 - 7.39 (m, 2 H) 7.45 (br d, J=7.6 Hz, 1 H) 7.50 (br d, J=8.0 Hz, 1 H) 7.59 (br d, J=8.0 Hz, 1 H) 7.69 - 7.83 (m, 1 H) 7.86 - 7.96 (m, 1 H) 8.00 - 8.10 (m, 1 H) 8.14 - 8.21 (m, 1 H) 8.31 - 8.38 (m, 1 H) 8.70 (br d, J=8.8 Hz, 1 H).

[0454] Example 64:

[0455] To a mixture of pneumocandin bO (700 mg, 657 pmol) and (3- bromophenyl)methanol (2.31 g, 9.86 mmol) in DMSO (10 mL) was added [(lS,4R)-7,7- dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (153 mg, 657 pmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:35%-65% B over 8.0 minutes) to give Example 64 (66.1 mg, 51.6 pmol, 7.85% yield) as a white solid. MS (fragment MS): 1163.6 ;1H NMR: MeOD 400 MHz 5 ppm 0.83 - 0.86 (m, 8 H) 0.89 (s, 1 H) 0.92 (br s, 1 H) 1.04 - 1.11 (m, 2 H) 1.13 - 1.18 (m, 3 H) 1.27 (br s, 15 H) 1.43 (br dd, J=12.8, 6.4 Hz, 2 H) 1.49 - 1.58 (m, 3 H) 1.94 (br dd, J=12.0, 6.4 Hz, 2 H) 2.01 - 2.07 (m, 2 H) 2.12 (br t, J=7.2 Hz, 2 H) 2.16 - 2.21 (m, 1 H) 2.42 - 2.46 (m, 1 H) 2.55 (br s, 1 H) 2.78 - 2.86 (m, 1 H) 3.76 - 3.83 (m, 2 H) 3.92 - 3.98 (m, 1 H) 3.99 - 4.06 (m, 1 H) 4.09 - 4.19 (m, 3 H) 4.28 (s, 3 H) 4.35 - 4.39 (m, 1 H) 4.53 - 4.60 (m, 4 H) 4.63 - 4.74 (m, 2 H) 4.94 - 5.04 (m, 2 H) 5.07 - 5.16 (m, 2 H) 5.21 - 5.30 (m, 1 H) 6.75 (d, J=8.4 Hz, 2 H) 6.80 (br d, J=8.4 Hz, 1 H) 7.12 - 7.19 (m, 3 H) 7.32 (br t, J=7.6 Hz, 1 H) 7.43 (br d, J=6.8 Hz, 1 H) 7.51 (br t, J=8.8 Hz, 2 H) 7.61 (s, 1 H) 7.73 - 7.81 (m, 1 H) 7.82 - 7.88 (m, 1 H) 8.05 - 8.17 (m, 1 H) 8.33 - 8.45 (m, 1 H) 8.60 - 8.72 (m, 1 H)

[0456] Example 65:

[0457] To a solution of Example 79 (300 mg, 250 pmol) in DMSO (3 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norboman-l-yl] methanesulfonic acid (58.2 mg, 250 pmol) and Ethanaminium, 2-mercapto-A,A,A-trimethyl-, iodide (722 mg, 2.5 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN];gradient:35%-65% B over 8.0 minutes) to give Example 65 (11.1 mg, 8.54 pmol, 2.92% yield, TFA) as a white solid. MS (M+H): 1300.7 ; ’H NMR: MeOD 400 MHz 5 ppm 0.9 (br d, J=6.4 Hz, 8 H) 0.9 (br s, 1 H) 0.9 (br s, 1 H) 1.0 - 1.1 (m, 3 H) 1.2 (br s, 2 H) 1.3 (br s, 12 H) 1.4 (br s, 2 H) 1.5 (br d, J=6.0 Hz, 2 H) 1.6 (br d, J=6.8 Hz, 3 H) 2.0 - 2.0 (m, 1 H) 2.0 - 2.1 (m, 1 H) 2.1 (br dd, J=8.8, 4.4 Hz, 1 H) 2.2 (br d, J=7.6 Hz, 1 H) 2.3 - 2.4 (m, 4 H) 2.5 - 2.6 (m, 3 H) 3.0 - 3.1 (m, 9 H) 3.2 (br d, J=6.8 Hz, 4 H) 3.5 - 3.6 (m, 2 H) 3.7 - 3.7 (m, 2 H) 3.8 - 3.8 (m, 2 H) 3.9 (br s, 3 H) 4.2 - 4.2 (m, 3 H) 4.3 - 4.4 (m, 3 H) 4.4 (br dd, J=8.4, 4.4 Hz, 1 H) 4.5 (br d, J=2.4 Hz, 2 H) 4.6 (br d, J=7.6 Hz, 2 H) 4.6 - 4.7 (m, 2 H) 5.1 (br s, 3 H) 5.4 (br s, 1 H) 6.9 (br d, J=8.8 Hz, 2 H) 7.0 (br d, J=9.2 Hz, 1 H) 7.3 (br d, J=8.4 Hz, 2 H) 7.4 (br d, J=7.6 Hz, 2 H) 7.6 (br d, J=7.6 Hz, 2 H) 7.7 - 7.8 (m, 1 H) 7.8 - 7.9 (m, 1 H) Example 66:

[0458] To a mixture of Example 77 (500 mg, 457 pmol) and 2-aminoethanol;hydrochloride (4.46 g, 45.7 mmol) in DMSO (8 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l- yl]methanesulfonic acid (106 mg, 457 pmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 48 hours. The reaction mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75*30mm*3pm;mobile phase: [H2O(0.1% TFA)- ACN];gradient:30%-60% B over 8.0 minutes) to give a crude product. The crude product was further purified by prep-HPLC (HC1 condition: column: Phenomenex luna C18 100 x 40mm x 5 pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 minutes) to give pure Example 66 (41.5 mg, 36.5 pmol, 7.99% yield) as a white solid. MS (M+H): 1136.6 ; ’H NMR: DMSO 400 MHz 5 ppm 0.80 (br d, J=5.6 Hz, 8 H) 0.83 (br s, 1 H) 0.85 - 0.90 (m, 1 H) 0.97 - 1.02 (m, 2 H) 1.03 - 1.09 (m, 1 H) 1.12 - 1.30 (m, 14 H) 1.36 (br s, 1 H) 1.44 (br d, J=5.2 Hz, 3 H) 1.75 - 1.91 (m, 3 H) 1.99 - 2.14 (m, 3 H) 2.15 - 2.28 (m, 2 H) 2.95 (br d, J=4.0 Hz, 2 H) 3.65 - 3.78 (m, 2 H) 3.93 - 4.03 (m, 2 H) 4.03 - 4.10 (m, 1 H) 4.10 - 4.17 (m, 1 H) 4.17 - 4.29 (m, 3 H) 4.30 - 4.44 (m, 2 H) 4.48 - 4.72 (m, 1 H) 4.75 - 4.85 (m, 1 H) 4.86 - 4.94 (m, 1 H) 7.22 (br s, 2 H) 7.36 - 7.44 (m, 1 H) 7.59 - 7.91 (m, 2 H) 8.27 - 8.35 (m, 1 H) 8.40 (br d, J=8.4 Hz, 1 H).

[0459] Example 67:

[0460] To a mixture of Example 77 (500 mg, 457 pmol) and 2-aminoethanol;hydrochloride (4.46 g, 45.7 mmol) in DMSO (8 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l- yl]methanesulfonic acid (106 mg, 457 pmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 48 hours. The reaction mixture was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3um;mobile phase: [H2O(0.1% TFA)- ACN];gradient:30%-60% B over 8.0 min) to give a crude product. The crude product was further purified by prep-HPLC (HC1 condition: column: Phenomenex luna Cl 8 100x40mmx5 um;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 min) to give Example 67 (34.4 mg, 30.3 pmol, 6.62% yield) as a white solid. MS (M+H): 1136.6 ; ’H NMR: DMSO 400 MHz 5 ppm 0.81 (br d, J=6.4 Hz, 8 H) 0.83 (br s, 1 H) 0.87 - 0.92 (m, 1 H) 0.98 - 1.03 (m, 2 H) 1.04 - 1.08 (m, 1 H) 1.12 (br d, J=5.6 Hz, 2 H) 1.17 - 1.27 (m, 13 H) 1.28 - 1.32 (m, 2 H) 1.37 (br d, J=6.8 Hz, 1 H) 1.40 - 1.47 (m, 3 H) 1.78 - 1.94 (m, 3 H) 2.01 - 2.12 (m, 3 H) 2.15 - 2.28 (m, 3 H) 2.90 - 3.01 (m, 2 H) 3.57 (br d, J=7.6 Hz, 2 H) 3.62 - 3.67 (m, 1 H) 3.68 - 3.80 (m, 3 H) 3.90 - 4.01 (m, 2 H) 4.11 - 4.15 (m, 1 H) 4.16 - 4.25 (m, 2 H) 4.26 - 4.33 (m, 2 H) 4.33 - 4.45 (m, 3 H) 4.47 - 4.62 (m, 2 H) 4.75 - 4.85 (m, 1 H) 4.92 (br d, J=7.2 Hz, 1 H) 7.13 - 7.27 (m, 2 H) 7.60 - 7.78 (m, 2 H).

[0461] Example 68:

[0462] To a solution of Example 79 (350 mg, 291 pmol) in DMSO (3 mL) were added [(IS, 4R)-7, 7-dimethyl-2-oxo-norboman-l-yl] methanesulfonic acid (67.8 mg, 291 pmol) and 2- (Isopropylamino)ethanol hydrochloride (4.08 g, 29.1 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 min) to give Example 68 (65 mg, 50.6 pmol, 17.3% yield, TFA) as a white solid. MS: (M+H): 1284.7 ; ’H NMR: MeOD 400 MHz 5 ppm 0.8 - 0.9 (m, 8 H) 0.9 (s, 1 H) 0.9 (br d, J=6.4 Hz, 1 H) 1.0 - 1.1 (m, 1 H) 1.1 (br d, J=7.2 Hz, 1 H) 1.2 - 1.2 (m, 2 H) 1.3 (br s, 4 H) 1.3 (br s, 5 H) 1.3 (br d, J=1.2 Hz, 5 H) 1.3 (br s, 3 H) 1.4 - 1.4 (m, 1 H) 1.5 - 1.5 (m, 1 H) 1.6 - 1.7 (m, 2 H) 1.9 - 2.0 (m, 2 H) 2.0 - 2.1 (m, 1 H) 2.1 - 2.3 (m, 3 H) 2.3 - 2.4 (m, 1 H) 2.4 - 2.4 (m, 2 H) 2.4 - 2.5 (m, 1 H) 2.5 - 2.6 (m, 1 H) 3.1 - 3.2 (m, 1 H) 3.2 (br d, J=2.4 Hz, 1 H) 3.4 - 3.4 (m, 1 H) 3.7 - 3.8 (m, 1 H) 3.8 - 3.8 (m, 1 H) 3.9 - 4.0 (m, 4 H) 4.0 (br dd, J=7.6, 3.0 Hz, 1 H) 4.2 - 4.2 (m, 3 H) 4.3 - 4.4 (m, 3 H) 4.4 - 4.5 (m, 1 H) 4.5 - 4.6 (m, 2 H) 4.6 - 4.6 (m, 1 H) 4.8 - 4.8 (m, 2 H) 4.9 (br d, J=4.4 Hz, 1 H) 5.1 - 5.1 (m, 2 H) 5.2 (br s, 1 H) 5.4 - 5.4 (m, 1 H) 7.0 (br d, J=8.4 Hz, 2 H) 7.0 (br d, J=8.4 Hz, 1 H) 7.3 - 7.3 (m, 2 H) 7.4 (br d, J=7.2 Hz, 1 H) 7.4 (br d, J=7.6 Hz, 2 H) 7.5 (br d, J=8.0 Hz, 1 H) 7.6 (br d, J=8.4 Hz, 1 H) 7.6 (d, J=8.0 Hz, 2 H) 7.8 (br d, J=7.6 Hz, 1 H) 7.9 (br d, J=7.6 Hz, 1 H).

[0463] Example 69:

[0464] To a solution of Example 77 (500 mg, 457 pmol) in DMSO (10 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (106 mg, 457 pmol) and 3-phenylpropan-l-ol (45.7 mmol, 6.2 mL) in one portion at 15°C, the reaction mixture was degassed and purged with N2for 3 times. The reaction mixture was heated to 30°C and stirred for 16 hours under N2atmosphere. After cooling to room temperature, the crude solvent was purified by prep-HPLC (column: Waters Xbridge Prep OBD Cl 8 150x40mmxl0pm;mobile phase: [H2O(10mM NH4HCO3)-ACN];gradient:45%-75% B over 8.0 minutes) to give crude product. The crude product was purified by prep-HPLC (column: Phenomenex luna C18 100 x 40m x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:30%-60% B over 8.0 min) to give pure Example 69 (59.8 mg, 48.3 pmol, 10.5% yield, 97.9% purity) as a white solid. MS: (M+H): 1212.6 ; ’H NMR: DMSO 400 MHz 5 = ppm 8.37 - 8.33 (m, 1 H), 8.25 (d, J= 2.4 Hz, 2 H), 7.82 (s, 1 H), 7.69 (d, J= 7.6 Hz, 2 H), 7.41 (d, J= 9.6 Hz, 1 H), 7.29 (d, J= 7.6 Hz, 1 H), 7.22 (d, J= 7.2 Hz, 2 H), 7.17 (d, J= 8.0 Hz, 1 H), 7.14 (d, J= 5.6 Hz, 4 H), 4.99 - 4.79 (m, 4 H), 4.47 - 4.26 (m, 5 H), 4.23 - 4.09 (m, 5 H), 4.08 - 3.93 (m, 6 H), 3.45 - 3.19 (m, 4 H), 2.58 - 2.53 (m, 3 H), 2.50 (s, 5 H), 2.32 - 2.17 (m, 3 H), 2.10 - 1.96 (m, 4 H), 1.83 (d, J = 9.2 Hz, 4 H), 1.76 - 1.66 (m, 4 H), 1.38 (d, J= 17.6 Hz, 5 H), 1.16 (s, 15 H), 0.96 (d, J= 5.6 Hz, 3 H), 0.79 - 0.75 (m, 12 H).

[0465] Example 70:

[0466] To a solution of Example 77 (500 mg, 457 pmol) in DMSO (10 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (106 mg, 457 pmol) and 2-(diethylamino)ethanol;hydrochloride (8.9 g, 46.9 mmol) in one portion at 15°C, the mixture was degassed and purged with N2for 3 times. The reaction mixture was heated to 30°C and stirred for 16 hours under N2atmosphere. After cooling to room temperature, the crude solvent was purified by prep-HPLC (column: Waters Xbridge Prep OBD Cl 8 150x40mmxl0pm;mobile phase: [H2O(10mM NH4HC03)-ACN];gradient:40%-70% B over 8.0 minutes) to give crude product. The crude product was further purified by prep-HPLC (column: Phenomenex luna C18 100 x 40mm x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:20%-50% B over 8.0 minutes) to give pure Example 70 (20.9 mg, 17 pmol, 3.74% yield, 97.5% purity) as a white solid. MS: (M+H): 1192.6 ; Hl NMR: DMSO 400 MHz 5 = ppm 8.50 - 8.28 (m, 2 H), 7.68 (d, J= 7.6 Hz, 2 H), 7.17 (d, J= 7.6 Hz, 2 H), 5.00 - 4.92 (m, 1 H), 4.90 - 4.83 (m, 1 H), 4.81 - 4.75 (m, 1 H), 4.40 (s, 1 H), 4.38 - 4.32 (m, 1 H), 4.31 - 4.22 (m, 2 H), 4.22 - 4.18 (m, 2 H), 4.17 - 4.09 (m, 3 H), 4.07 - 3.95 (m, 3 H), 3.94 - 3.82 (m, 2 H), 3.66 - 3.52 (m, 5 H), 3.27 - 3.18 (m, 2 H), 3.15 - 2.99 (m, 6 H), 2.26 - 2.15 (m, 3 H), 2.08 (d, .7= 6.4 Hz, 3 H), 1.91 - 1.70 (m, 5 H), 1.51 - 1.31 (m, 6 H), 1.23 - 1.10 (m, 24 H), 1.03 - 0.93 (m, 5 H), 0.82 - 0.76 (m, 12 H).

[0467] Example 71:

[0468] To a solution of Example 77 (500 mg, 457 pmol) and [(IS, 4R)-7, 7-dimethyl-2-oxo- norboman-l-yl] methanesulfonic acid (106 mg, 457 pmol) in DMSO (5 mL) was added 2-(- (Isopropylamino)ethanol hydrochloride (6.39 g, 45.7 mmol). The reaction mixture was heated to 30°C and stirred for 40 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 minutes) to afford Example 71 (101.5 mg, 86.15 pmol, 18.8% yield, TFA) as a white solid. MS: (M+H): 1178.6 ; *H NMR: MeOD 400 MHzS ppm 0.8 - 0.9 (m, 8 H) 0.9 (s, 1 H) 0.9 (br d, .7=6,4 Hz, 1 H) 1.0 - 1.1 (m, 2 H) 1.1 (br d, J=6.8 Hz, 1 H) 1.2 (br d, J=6.0 Hz, 1 H) 1.2 - 1.3 (m, 2 H) 1.3 - 1.4 (m, 20 H) 1.4 - 1.5 (m, 2 H) 1.5 (br d, J=6.8 Hz, 1 H) 1.6 (br d, J=6.8 Hz, 2 H) 2.1 (br dd, J=10.4, 4.0 Hz, 1 H) 2.2 - 2.3 (m, 2 H) 2.3 (br d, 7=7.2 Hz, 1 H) 2.4 (br dd, 7=8.4, 4.8 Hz, 1 H) 2.5 - 2.5 (m, 1 H) 2.7 (br dd, 7=15.2, 3.6 Hz, 1 H) 3.2 (br d, 7=4.8 Hz, 2 H) 3.4 - 3.5 (m, 2 H) 3.7 - 3.8 (m, 3 H) 3.9 (br dd, 7=9.2, 6.4 Hz, 1 H) 3.9 - 4.0 (m, 2 H) 4.1 - 4.2 (m, 1 H) 4.2 (br d, 7=3.6 Hz, 1 H) 4.3 - 4.4 (m, 4 H) 4.4 (br d, 7=7.2 Hz, 1 H) 4.5 - 4.5 (m, 1 H) 4.6 (br d, 7=7.2 Hz, 2 H) 5.0 (br dd, 7=8.4, 3.2 Hz, 1 H) 5.1 - 5.1 (m, 1 H) 5.2 (br d, 7=3.6 Hz, 1 H) 5.3 - 5.3 (m, 1 H) 7.3 (br d, 7=8.0 Hz, 1 H) 7.4 (br s, 1 H) 7.5 (br d, 7=7.6 Hz, 1 H) 7.5 (br d, 7=8.4 Hz, 1 H)

[0469] 7.6 (br d, 7=7.6 Hz, 1 H) 7.7 (br d, 7=7.6 Hz, 1 H) 8.0 (br d, 7=8.0 Hz, 1 H) 8.1 - 8.2 (m, 1 H)

[0470] 8.6 - 8.8 (m, 1 H).

[0471] Example 72:

[0472] To a solution of Example 77 (400 mg, 365 pmol) and [(lS,4R)-7,7-dimethyl-2-oxo- norboman-l-yl] methanesulfonic acid (85 mg, 365 pmol) in DMSO (4 mL) was added 3- Pyridinemethanol (399 mg, 3.66 mmol) at 20°C. The reaction mixture was heated to 50°C and stirred for 96 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:30%-60% B over 8.0 minutes) to give Example 72 (21.1 mg, 17.8 pmol, 4.87% yield) as a white solid. MS: (M+H): 1184.6 ; ’H NMR: DMSO 400 MHz 5 ppm 0.8 (d, J=6.4 Hz, 8 H) 0.8 (s, 1 H) 0.9 - 0.9 (m, 1 H) 1.0 (br d, J=6.0 Hz, 1 H) 1.0 (br d, J=5.6 Hz, 3 H) 1.1 - 1.1 (m, 1 H) 1.2 (br s, 2 H) 1.2 (br s, 9 H) 1.3 - 1.3 (m, 2 H) 1.3 - 1.4 (m, 2 H) 1.4 (br s, 1 H) 1.5 (br s, 2 H) 1.8 - 1.9 (m, 2 H) 2.0 (br dd, J=12.4, 4.8 Hz, 2 H) 2.1 - 2.2 (m, 1 H) 2.2 (br d, J=6.8 Hz, 1 H) 2.2 (br s, 1 H) 2.3 (br d, J=7.2 Hz, 1 H) 2.4 (br dd, J=15.2, 3.6 Hz, 1 H) 3.7 (br d, J=9.6 Hz, 1 H) 3.8 (br s, 1 H) 3.9 - 3.9 (m, 1 H) 4.0 (br dd, J=7.6, 1.6 Hz, 1 H) 4.0 - 4.1 (m, 1 H) 4.1 (br dd, J=5.2, 2.8 Hz, 2 H) 4.1 (br s, 1 H) 4.3 (br d, J=7.6 Hz, 1 H) 4.3 (br s, 1 H) 4.4 (br d, J=2.4 Hz, 2 H) 4.5 (br d, J=13.2 Hz, 1 H) 4.6 - 4.6 (m, 1 H) 4.8 (s, 2 H) 4.8 - 4.9 (m, 2 H) 6.5 (br d, J=7.2 Hz, 1 H) 6.7 (d, J=8.4 Hz, 1 H) 7.0 (br d, J=8.4 Hz, 1 H) 7.2 - 7.2 (m, 3 H) 7.4 (br d, J=9.6 Hz, 1 H) 7.7 (d, J=8.0 Hz, 2 H) 8.1 - 8.2 (m, 1 H) 8.3 - 8.4 (m, 1 H) 8.5 - 8.6 (m, 2 H) 8.7 - 8.8 (m, 2 H) 9.9 (br d, J=7.2 Hz, 1 H).

[0473] Example 73:

[0474] To a solution of Example 77 (500 mg, 457.4 pmol) in DMSO (8 mL) were added phenylmethanol (989 mg, 9.15 mmol) and [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l- yl]methanesulfonic acid (106 mg, 457 pmol) at 20°C. The reaction mixture was heated to 30°C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (column: Phenomenex luna Ci8 100 x 40mm x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:35%-65% B over 8.0 minutes) to give Example 73 (119.9 mg, 101 pmol, 22.1% yield) as a white solid. MS (M+H): 1183.6 ;XH NMR: DMSO 400 MHz 5 = ppm 8.30 - 8.20 (m, 2 H), 7.68 (d, J= 8.0 Hz, 2 H), 7.22 (d, J= 7.2 Hz, 2 H), 7.18 - 7.12 (m, 5 H), 4.98 (d, J= 10.0 Hz, 1 H), 4.90 - 4.84 (m, 1 H), 4.78 (d, J= 8.4 Hz, 1 H), 4.41 (s, 1 H), 4.37 - 4.24 (m, 3 H), 4.19 (d, J= 8.0 Hz, 1 H), 4.16 - 4.08 (m, 4 H), 4.03 (t, J= 7.2 Hz, 2 H), 3.96 (d, J= 8.4 Hz, 1 H), 3.60 - 3.54 (m, 2 H), 2.77 - 2.70 (m, 2 H), 2.26 - 2.02 (m, 6 H), 1.91 - 1.77 (m, 4 H), 1.46 - 1.32 (m, 5 H), 1.24 - 1.12 (m, 15 H), 1.03 - 0.94 (m, 5 H), 0.80 - 0.75 (m, 10 H) Example 74:

[0475] To a solution of Example 77 (500 mg, 457 pmol) in DMSO (8 mL) were added 2- phenylethanol (1.12 g, 9.15 mmol) and [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l- yl]methanesulfonic acid (106 mg, 457 pmol) at 20°C. The reaction mixture was heated to 30°C and stirred for 16 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 pm;mobile phase: [H20(0.04% HC1)- ACN];gradient:35%-65% B over 8.0 minutes) to give Example 74 (81.9 mg, 68.4 pmol, 14.9% yield) as a white solid. MS (M+H): 1197.6 ; ’H NMR: DMSO 400 MHz 5 = ppm 8.30 - 8.20 (m, 2 H), 7.68 (d, J= 8.0 Hz, 2 H), 7.22 (d, J= 7.2 Hz, 2 H), 7.18 - 7.12 (m, 5 H), 4.98 (d, J= 10.0 Hz, 1 H), 4.90 - 4.84 (m, 1 H), 4.78 (d, J= 8.4 Hz, 1 H), 4.41 (s, 1 H), 4.37 - 4.24 (m, 3 H), 4.19 (d, J= 8.0 Hz, 1 H), 4.16 - 4.08 (m, 4 H), 4.03 (t, J= 7.2 Hz, 2 H), 3.96 (d, J= 8.4 Hz, 1 H), 3.60 - 3.54 (m, 2 H), 2.77 - 2.70 (m, 2 H), 2.26 - 2.02 (m, 6 H), 1.91 - 1.77 (m, 4 H), 1.46 - 1.32 (m, 5 H), 1.24 - 1.12 (m, 15 H), 1.03 - 0.94 (m, 5 H), 0.80 - 0.75 (m, 10 H).

[0476] Example 75:

[0477] To a mixture of Example 77 (500 mg, 457 pmol) and 2-pyridylmethanol (499 mg, 4.57 mmol) in DMSO (5 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l- yl]methanesulfonic acid (106 mg, 457 pmol) in one portion at 25°C. The reaction mixture was heated and stirred at 50°C for 96 hours. After cooling to room temperature, the mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (TFA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [H2O(0.1% TFA)-ACN];gradient:25%-55% B over 8.0 minutes) to give Example 75 (51.1 mg, 43.2 pmol, 9.43% yield) as a white solid. MS (M+H): 1184.6 ; ’H NMR: DMSO 400 MHz 5 ppm 0.74 - 0.81 (m, 8 H) 0.81 - 0.84 (m, 1 H) 0.84 - 0.90 (m, 1 H) 0.98 (br d, J=6.0 Hz, 3 H) 1.02 (br d, .7=6.0 Hz, 1 H) 1.04 - 1.26 (m, 14 H) 1.27 - 1.32 (m, 1 H) 1.33 - 1.45 (m, 4 H) 1.70 - 1.96 (m, 4 H) 1.96 - 2.11 (m, 3 H) 2.12 - 2.30 (m, 3 H) 3.64 - 3.80 (m, 2 H) 3.87 - 4.04 (m, 3 H) 4.05 - 4.18 (m, 3 H) 4.21 (br d, .7=2,0 Hz, 1 H) 4.25 - 4.31 (m, 1 H) 4.31 - 4.37 (m, 1 H) 4.40 (br s, 1 H) 4.56 - 4.71 (m, 2 H) 4.79 (br d, J=9.6 Hz, 1 H) 4.85 - 4.95 (m, 1 H) 5.08 (br d, J=8.8 Hz, 1 H) 7.18 (br d, J=8.0 Hz, 2 H) 7.35 - 7.45 (m, 1 H) 7.46 - 7.54 (m, 1 H) 7.59 - 7.73 (m, 2 H) 7.95 - 8.09 (m, 1 H) 8.32 - 8.43 (m, 1 H) 8.58 (br d, J=5.6 Hz, 1 H).

[0478] Example 76:

[0479] To a mixture of Example 77 (500 mg, 457 pmol) and phenylmethanethiol (1.89 g, 15.2 mmol) in DMSO (5 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l- yl]methanesulfonic acid (106 mg, 457 pmol, 1.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna C18 75x30mmx3pm;mobile phase: [H2O(0.1% TFA)- ACN];gradient:45%-75% B over 8.0 minutes) to give crude product. The crude product was further purified by prep-HPLC (HC1 condition: column: Phenomenex luna Cl 8 100 x 40mm x 5pm;mobile phase: [H20(0.04% HCl)-ACN];gradient:30%-60% B over 8.0 minutes) to give pure Example 76 (58.3 mg, 48.6 pmol, 10.6% yield) as a white solid. MS (M+H): 1199.6 ; ’H NMR: DMSO 400 MHz 5 ppm 0.79 (dd, J=6.4, 2.8 Hz, 8 H) 0.82 - 0.84 (m, 1 H) 0.84 - 0.90 (m, 1 H) 0.92 - 1.02 (m, 4 H) 1.03 - 1.08 (m, 1 H) 1.08 - 1.34 (m, 15 H) 1.35 - 1.48 (m, 4 H) 1.69 - 1.96 (m, 4 H) 1.97 - 2.11 (m, 3 H) 2.14 - 2.28 (m, 2 H) 3.51 - 3.60 (m, 1 H) 3.64 - 3.84 (m, 4 H) 3.86 - 4.04 (m, 3 H) 4.04 - 4.11 (m, 2 H) 4.13 - 4.22 (m, 3 H) 4.25 - 4.32 (m, 1 H) 4.33 - 4.44 (m, 2 H) 4.77 - 4.99 (m, 2 H) 5.13 - 5.26 (m, 1 H) 7.19 (br d, .7=7,6 Hz, 3 H) 7.23 - 7.35 (m, 5 H) 7.42 (br d, J=10.0 Hz, 1 H) 7.70 (d, J=8.0 Hz, 1 H) 7.80 - 7.87 (m, 1 H) 8.22 (br d, J=8.0 Hz, 1 H) 8.39 - 8.57 (m, 2 H).

[0480] Example 77:

[0481] To a solution of pneumocandin bO (5 g, 4.70 mmol) in THF(42 mL) and DMF (7 mL) was added Cs2CO3(3.05 g, 9.40 mmol) in one portion at 15°C under N2atmosphere. Then 1,1,1 -trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (Tf2NPh, 2.52 g, 7.05 mmol) was added to the reaction mixture in portions at -10°C. The reaction mixture was warmed to 15°C and stirred for 16 hours. This reaction was repeated and the two reactions were combined to work up. The combined mixture were quenched by addition of H2O (20 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic layers were washed with brine (30 mL x 3), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (neutral condition: column: Welch Xtimate C18 250 x 100mm#10pm;mobile phase: [water( NH4HC03)-ACN];gradient:40%-70% B over 20 minutes) to give Intermediate 1 (3.3 g, 2.76 mmol, 29.3% yield, 66% purity) as a white solid.

[0482] To a solution of crude Intermediate 1 (1 g, 835 pmol) in DMA (10 mL) were added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (B2Pin2, 636 mg, 2.51 mmol), KO Ac (163 mg, 1.67 mmol, 2 eq) and [2-(2- aminophenyl)phenyl]palladium(l+);bis(l-adamantyl)-butyl-phosphane;methanesulfonate (304 mg, 417 pmol) in one portion at 15°C under N2atmosphere. The system was degassed and purged with N23 times. The reaction mixture was heated to 80°C and stirred for 2 hr under N2atmosphere. After cooling to room temperature, the mixture was filtered and the filter cake was washed with ethyl acetate (10 mL x 3), then filtrate was concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (neutral condition: column: Waters Xbridge Prep OBD C18 150 x 40mm x 10pm;mobile phase: [water( NH4HCO3)-ACN];B%: 40%-60%, 8 minutes) to afford a crude product, which was further purified by prep-HPLC (neutral condition: column: Waters Xbridge Prep OBD C18 150 x 40mm x 10pm;mobile phase: [water( NH4HCO3)-ACN];B%: 40%-65%,8 minutes) to afford pure Example 77 (79.2 mg, 73.1 pmol, 8.67% yield) as a white solid. MS (M+H): 1093.6 ; ’H NMR: DMS0400 MHzS ppm 0.81 (br d, J=6.0 Hz, 11 H) 0.85 - 0.93 (m, 1 H) 1.06 (dt, .7=13.6, 6.8 Hz, 4 H) 1.17 (br d, J=7.6 Hz, 3 H) 1.23 (br s, 13 H) 1.33 - 1.40 (m, 2 H) 1.47 (br d, .7=13.2 Hz, 2 H) 1.81 (br s, 1 H) 1.93 - 2.02 (m, 2 H) 2.12 (br s, 3 H) 2.22 (br d, J=7.6 Hz, 1 H) 2.34 (br s, 2 H) 3.56 - 3.67 (m, 2 H) 3.73 (br d, J=4.8 Hz, 2 H) 3.92 - 4.02 (m, 3 H) 4.15 (br d, .7=14.8 Hz, 2 H) 4.23 - 4.38 (m, 3 H) 4.44 - 4.61 (m, 5 H) 4.64 (br s, 1 H) 4.73 (br s, 1 H) 5.11 (br s, 1 H) 5.40 - 5.75 (m, 1 H) 6.67 - 7.06 (m, 2 H) 7.21 (br s, 1 H) 7.24 - 7.36 (m, 2 H) 7.65 (br d, J=7.6 Hz, 1 H) 7.71 (br d, J=7.2 Hz, 1 H) 7.82 - 7.96 (m, 1 H).

[0483] Example 78:

[0484] To a solution of pneumocandin bO (4 g, 3.76 mmol) in HOAc (100 mL) and TFA (20 mL) was added NaBH3CN (2.48 g, 39.4 mmol) in one portion at 25°C under N2atmosphere. The reaction mixture was stirred at 25°C for 16 hours. This reaction was repeated and the two reactions were combined concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Welch Xtimate C18 250 x 70mm x 10pm; mobile phase: [water(TFA)-ACN];B%: 35%-65%, 8 minutes) to give Intermediate 1 (2.23 g, 2.12 mmol, 28.3% yield) as a white solid.

[0485] To a solution of Intermediate 1 (2.23 g, 2.12 mmol) in THF (20 mL) and DMF (3 mL) was added Cs2CO3(1.38 g, 4.24 mmol) in one portion at -10°C under N2atmosphere. Then l,l,l-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.14 g, 2.61 mmol) was added to the reaction mixture in portions at -10°C. The reaction mixture was warmed to 20°C and stirred for 16 hours. The mixture was quenched by addition of H2O (100 mL) and extracted with ethyl acetate (80 mL x 3). The combined organic phases were washed with brine (30 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC ((neutral condition: column: Waters Xbridge Prep OBD C18 150 x 40mm x 10pm;mobile phase: [water( NH4HCO3)-ACN];B%: 45%-65%, 8 minutes) to give Intermediate 2 (690 mg, 584 umol, 27.4% yield) as a white solid.

[0486] To a solution of Intermediate 2 (600 mg, 507 umol) in DMA (6 mL) were added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (412 mg, 1.62 mmol), KOAc (101 mg, 1.01 mmol) and Catacxium A-Pd-G3 (185 mg, 252 umol) in one portion at 25°C under N2atmosphere. The reaction mixture was degassed and purged with N2for 3 times. Then the reaction mixture was heated to 80°C and stirred for 2 hours under N2atmosphere. After cooling to room temperature, the mixture was quenched by addition of H2O (30 mL) and extracted with ethyl acetate (30 mL x 3). The combined organic phases were washed with brine (15 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (FA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [water(FA)-ACN];B%: 30%-70%, 8 minutes) to give Intermediate 3 (120 mg, 103 umol, 20.3% yield) as a white solid.

[0487] To a solution of Intermediate 3 (190 mg, 129 umol) in TFA (0.8 mL) and DCM (4 mL) was added MeB(OH)2(77 mg, 1.29 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 2 hours. The mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (FA condition: column: Phenomenex Luna C18 75 x 30mm x 3pm;mobile phase: [water(FA)-ACN];B%: 30%-70%, 8 minutes) to give Example 78 (69.3 mg, 64.3 pmol, 49.2% yield) as a white solid. MS (M+H): 1077.6 ; ’H NMR: DMS0400 MHz 5 ppm 0.79 (d, J=6.0 Hz, 8 H) 0.82 (br s, 1 H) 0.86 - 0.90 (m, 1 H) 0.97 (br d, J=6.0 Hz, 3 H) 1.03 - 1.07 (m, 1 H) 1.15 - 1.25 (m, 14 H) 1.28 (br s, 1 H) 1.36 - 1.46 (m, 4 H) 1.72 - 1.80 (m, 2 H) 1.81 - 1.89 (m, 2 H) 2.03 - 2.10 (m, 3 H) 2.16 - 2.25 (m, 2 H) 2.44 (br d, J=4.4 Hz, 1 H) 3.57 (br d, J=1.2 Hz, 1 H) 3.76 (br d, J=9.2 Hz, 1 H) 3.79 - 3.85 (m, 1 H) 3.88 - 3.94 (m, 1 H) 3.97 - 4.03 (m, 1 H) 4.09 (br d, J=1.2 Hz, 1 H) 4.11 - 4.18 (m, 4 H) 4.26 (br d, J=7.2 Hz, 1 H) 4.27 - 4.35 (m, 2 H) 4.39 (br s, 1 H) 4.74 - 4.82 (m, 1 H) 4.84 - 4.91 (m, 1 H) 4.94 - 5.03 (m, 1 H) 5.41 (s, 2 H) 7.16 (br d, J=8.8 Hz, 2 H) 7.24 - 7.29 (m, 2 H) 7.39 (dd, J=8.0, 1.6 Hz, 1 H) 7.46 (d, J=1.6 Hz, 1 H) 7.62 (d, J=7.6 Hz, 1 H) 8.13 - 8.36 (m, 2 H).

[0488] Example 79:

[0489] To a solution of pneumocandin bO (200 mg, 188 umol) in DMF (2 mL) were added LiOH (5.40 mg, 225 umol) and 2-[4-(bromomethyl)phenyl]-4,4,5,5-tetramethyl-l,3,2- dioxaborolane (55.7 mg, 188 umol). The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched by addition of H2O (1 mL) at 25°C. This reaction was repeated a total of 10 times. The combined 10 reaction mixtures were purified directly by prep-HPLC (Phenomenex luna C18 (250 x 70mm, 15 pm); mobile phase: [water (FA)-ACN]; B%: 45%-75%, 20 minutes) to give crude product, which was further purified by prep-HPLC (TFA condition: column: column: Phenomenex Luna 80 x 30mm x 3 pm; mobile phase: [water (TFA)-ACN]; B%: 30%-60%, 8 minutes) to give Example 79 (200 mg, 167 umol, 8.88% yield) as a white solid. MS (fragment): 1163.6 ; ’H NMR: DMSO 400 MHz 5 = 0.8 (br d, J=5.6 Hz, 8 H) 0.88 (br d, J=6.4 Hz, 3 H) 0.96 - 1.08 (m, 4 H) 1.20 (br d, J=6.4 Hz, 17 H) 1.40 - 1.52 (m, 5 H) 1.84 - 1.96 (m, 3 H) 2.08 (br dd, J=14.8, 7.6 Hz, 2 H) 2.18 (br dd, J=14, 8.4 Hz, 3 H) 2.36 - 2.40 (m, 1 H) 3.68 - 3.76 (m, 3 H) 3.80 - 4.00 (m, 5 H) 4.12 (s, 1 H) 4.16 (br d, J=10.8 Hz, 2 H) 4.28 (br s, 1 H) 4.32 - 4.40 (m, 3 H) 4.48 (br dd, J=12.0, 7.0 Hz, 2 H) 4.60 (br d, J=7.6 Hz, 3 H) 4.72 (br d, J=6.0 Hz, 1 H) 5.04 - 5.12 (m, 3 H) 5.32 (br d, J=7.6 Hz, 1 H) 6.52 - 6.72 (m, 1 H) 6.76 (br d, J=7.0 Hz, 1 H) 6.84 - 6.88 (m, 1 H) 6.96 - 7.08 (m, 1 H) 7.12 - 7.20 (m, 2 H) 7.24 - 7.32 (m, 2 H) 7.40 (br d, J=7.2 Hz, 1 H) 7.52 (br s, 1 H) 7.68 - 7.88 (m, 3 H) 7.92 - 8.08 (m, 1 H) 8.20 - 8.40 (m, 1 H).

[0490] Example 80:

[0491] To a solution of pneumocandin bO (2.5 g, 2.35 mmol) in DMF (50 mL) was added DIEA (11.73 mmol, 2.04 mL) and (4-nitrophenyl) carbonochloridate (2.37 g, 11.73 mmol) in one portion at 0°C under N2atmosphere. The reaction mixture was stirred at 0°C and stirred for 2 hours. After warming to room temperature, the reaction mixture (as a DMF solution) was purified by prep-HPLC (TFA condition: column: Phenomenex Luna 80 x 30mm x 3pm;mobile phase: [water(TFA)-ACN];B%: 40%-70%, 8minutes) to give compound Intermediate 1 (750 mg, 705 umol, 25.9% yield) as a white solid.

[0492] To a solution of 5-Chloro-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)benzaldehyde (2.00 g, 7.50 mmol) in MeOH (20.0 mL) was added NaBH4(341 mg, 9.00 mmol) slowly in portions at 0°C under N2atmosphere. The system was degassed and then charged with nitrogen three times. The reaction mixture was warmed to 25°C and stirred for 2 hours. The reaction mixture was diluted with H2O (50 mL) and extracted with ethyl acetate (50 mL x 3). The combined organic layers were dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give Reagent 1 (1.70 g, crude) as a white solid, which was used without further purification.

[0493] To a solution of Reagent 1 (120 mg, 447 umol) in DMF (5 mL) was added DIEA (1.22 mmol, 212 uL) in one portion at 25°C. The reaction mixture was stirred at 25°C for 15 minutes. Then Intermediate 1 (500 mg, 406 umol) was added to the reaction and the reaction mixture was stirred at 25°C for 16 hours. The reaction was purified by prep-HPLC (FA condition: column: column: Phenomenex Luna Cl 8 200 x 40mm x 10pm; mobile phase: [water (FA)-ACN]; B%: 50%-90%, 8 minutes) to give Intermediate 2 (60.0 mg, 44.1 pmol, 10.8% yield) as a white solid.

[0494] To a solution of Intermediate 2 (240 mg, 176 umol) in TFA (0.2 mL) and DCM (3.8 mL) was added MeB(OH)2(105 mg, 1.76 mmol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 2 hours. The reaction mixture was concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Phenomenex Luna 80 x 30mm x 3pm; mobile phase: [water (TFA)-ACN]; B%: 30%-60%, 8 minutes) to give Example 80 (64.8 mg, 60.7 umol, 31.1% yield) as a white solid. MS (fragment MS): 1343.7 ; ’H NMR: DMSO 400 MHz 5 = 0.79 (d, .7=6,4 Hz, 8 H) 0.82 (br s, 1 H) 0.86 - 0.90 (m, 1 H) 0.97 (br d, J=6.0 Hz, 3 H) 1.03 - 1.07 (m, 1 H) 1.15 - 1.25 (m, 14 H) 1.28 (br s, 1 H) 1.36 - 1.46 (m, 4 H) 1.72 - 1.80 (m, 2 H) 1.81 - 1.89 (m, 2 H) 2.03 - 2.10 (m, 3 H) 2.16 - 2.25 (m, 2 H) 2.44 (br d, .7=4,4 Hz, 1 H) 3.57 (br d, J=1.2 Hz, 1 H) 3.76 (br d, .7=9,2 Hz, 1 H) 3.79 - 3.85 (m, 1 H) 3.88 - 3.94 (m, 1 H) 3.97 - 4.03 (m, 1 H) 4.09 (br d, J=1.2 Hz, 1 H) 4.11 - 4.18 (m, 4 H) 4.26 (br d, J=7.6 Hz, 1 H) 4.27 - 4.35 (m, 2 H) 4.39 (br s, 1 H) 4.74 - 4.82 (m, 1 H) 4.84 - 4.91 (m, 1 H) 4.94 - 5.03 (m, 1 H) 5.41 (s, 2 H) 7.16 (br d, 7=8.4 Hz, 2 H) 7.24 - 7.29 (m, 2 H) 7.39 (dd, 7=8.0, 1.6 Hz, 1 H) 7.46 (d, 7=1.6 Hz, 1 H) 7.62 (d, 7=7.6 Hz, 1 H) 8.13 - 8.36 (m, 2 H).

[0495] Example 81:

[0496] To a mixture of Example 80 Reagent 1 (1.00 g, 4.27 mmol) and bis(4-nitrophenyl) carbonate (1.56 g, 5.13 mmol) in DMF (10.0 mL) was added DIEA (17.1 mmol, 2.98 mL) in one portion at 20°C. The reaction mixture was stirred at 20°C for 4 hours. The reaction mixture was diluted with H2O 60 mL and extracted with ethyl acetate (50 mL x 3). The combined organic layers were washed with brine (40 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by column chromatography (SiO2, Petroleum ether / Ethyl acetate = 100 / 0 to 80 / 20) to give Reagent 2 (2.10 g, crude) as a white solid.

[0497] To a solution of pneumoncandin bO (500 mg, 469 umol, 1.00 eq) in DMF (5 mL) was added K2CO3(130 mg, 939 umol, 2.00 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 15 minutes. Then was added Reagent 2 (206 mg, 516 umol, 1.10 eq) and stirred at 25°C for 16 hours. The reaction was straightly purified by prep-HPLC (FA condition: column: Phenomenex Luna C18 200 x 40mm x 10pm; mobile phase: [water (FA)- ACN]; B%: 40%-65%, 8 minutes) to give Example 81 (201 mg, 161 umol, 34.3% yield) as a white solid. MS (fragment MS): 1225.4 ; ’H NMR: MeOD 400 MHz 5 = 0.80 - 0.83 (m, 8 H) 0.84 (br s, 1 H) 0.89 (br d, 7=6.4 Hz, 1 H) 0.97 - 1.09 (m, 4 H) 1.16 - 1.30 (m, 17 H) 1.36 - 1.49 (m, 5 H) 1.75 - 1.88 (m, 3 H) 2.07 (br t, 7=6.4 Hz, 3 H) 2.16 - 2.26 (m, 2 H) 2.29 - 2.40 (m, 1 H) 3.50 - 3.64 (m, 2 H) 3.72 (br s, 1 H) 3.74 - 3.87 (m, 2 H) 3.91 - 4.03 (m, 2 H) 4.08 - 4.13 (m, 1 H) 4.14 - 4.23 (m, 3 H) 4.32 (br d, 7=11.2 Hz, 2 H) 4.35 - 4.44 (m, 2 H) 4.49 (br dd, 7=7.6, 4.8 Hz, 1 H) 4.58 - 4.65 (m, 1 H) 4.71 (br d, 7=5.6 Hz, 1 H) 4.74 - 4.82 (m, 1 H) 4.86 - 4.98 (m, 2 H) 5.05 - 5.14 (m, 2 H) 5.17 (br dd, 7=9.2, 3.6 Hz, 1 H) 5.24 - 5.31 (m, 2 H) 5.34 (br s, 1 H) 5.41 (br dd, 7=8.8, 5.6 Hz, 1 H) 6.67 - 6.79 (m, 1 H) 6.80 - 6.96 (m, 1 H) 7.09 (br s, 1 H) 7.13 - 7.21 (m, 2 H) 7.26 - 7.32 (m, 2 H) 7.40 (br d, 7=7.6 Hz, 2 H) 7.51 (br d, 7=6.4 Hz, 1 H) 7.80 - 7.91 (m, 2 H) 8.03 - 8.15 (m, 2 H) 8.17 - 8.30 (m, 1 H). Example 82:

[0498] To a mixture of l,3-dihydro-l-hydroxy-2,l-benzoxaborol-6-ol (46.6 g, 310.79 mmol) in DMF (460 mL) was added TEA (94.35 g, 932.38 mmol) dropwise at 20°C. The mixture was cooled to 0°C. To the mixture was added bis(4-nitrophenyl) carbonate (179.64 g, 590.51 mmol) in portions at 0°C. Then the mixture was warmed to 20°C and stirred at 20°C for 2 hours. The reaction mixture was added water (1300 mL) at 20°C. The resulting solid was filtered under reduced pressure. The resulting solid was triturated with MeCN (40 mL) at 20°C for 10 minutes and filtered to give Reagent 1 (74 g, 234.89 mmol, 75.58% yield) as a white solid.

[0499] To the mixture of pneumocandin bO (72.13 g, 67.72 mmol) in DMF (1500 mL) was added DMAP (8.27 g, 67.72 mmol) and TEA (13.70 g, 135.43 mmol) in portions at 20°C. The mixture was cooled to 0°C and to the above mixture was added Reagent 1 (32 g, 101.57 mmol, 1.5 eq) in portions at 0°C. Then the mixture was warmed to 20°C and stirred at 20°C for 16 hours. The reaction mixture was added water (4500 mL) and adjusted pH=6 with 1 M HC1 at 0°C. The resulting solid was filtered under reduced pressure and the resulting solid was purified by Prep-HPLC(column: Phenomenex luna cl8 250mm x 100mm x 10pm;mobile phase: [H20(0.2%FA)-ACN];gradient:40%-62% B over 20.0 minutes) to give Example 82 (41.65 g, 33.56 mmol, 28.92% yield) as a white solid. MS: (M-OH): 1223.4 ; ’H NMR: DMSO 400 MHz 5 ppm 9.35 (s, 1H), 8.31 (d, J = 7.6 Hz, 1H), 8.27-8.20 (m, 1H), 8.10 (d, J = 8.8 Hz, 1H), 7.65 (d, J= 1.2 Hz, 1H), 7.53-7.47 (m, 2H), 7.46-7.42 (m, 1H), 7.33 (s, 4H), 7.30-7.26 (m, 2H), 6.75 (s, 1H), 5.43 (s, 1H), 5.20-5.06 (m, 2H), 5.01 (s, 4H), 4.91- 4.87 (m, 1H), 4.78 (d, J= 6.8 Hz, 1H), 4.40 (s, 1H), 4.36-4.30 (m, 3H), 4.21 (s, 1H), 4.17 (s, 3H), 4.15-4.07 (m, 2H), 4.04-3.95 (m, 2H), 3.83-3.77 (m, 1H), 3.72 (s, 2H), 3.62-3.54 (m, 2H), 2.25-2.16 (m, 2H), 2.10-2.05 (m, 3H), 1.89-1.81 (m, 2H), 1.80-1.72 (m, 2H), 1.49-1.39 (m, 4H), 1.27-1.17 (m, 15H), 1.08-0.99 (m, 6H), 0.92-0.86 (m, 1H), 0.84-0.80 (m, 10H).

[0500] Example 83:

[0501] To a solution of pneumocandin bO (2.5 g, 2.35 mmol) in DMF (50 mL) was added DIEA (11.73 mmol, 2.04 mL) and (4-nitrophenyl) carbonochloridate (2.37 g, 11.73 mmol) in one portion at 0°C under N2atmosphere. The reaction mixture was stirred at 0°C and stirred for 2 hours. After warming to room temperature, the reaction mixture was straightly (DMF solution) purified by prep-HPLC (TFA condition: column: Phenomenex Luna 80x30mmx3pm;mobile phase: [water(TFA)-ACN];B%: 40%-70%, 8 minutes) to give compound Intermediate 1 (750 mg, 705 umol, 25.9% yield) as a white solid.

[0502] To a solution of l,3-Dihydro-l-hydroxy-2,l-benzoxaborol-6-amine (72.6 mg, 488 umol) in DMF (5 mL) were added pyridine (1.22 mmol, 98.4 uL) and Intermediate 1 (500 mg, 406 umol) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched with 5 mg acetic acid and it was straightly purified by prep-HPLC (FA condition: column: Phenomenex Luna C18 75 x 30mm x 3um; mobile phase: [water(FA)-ACN]; B%: 45%-75%, 8 min) to give Example 83 (210 mg, 161 umol, 39.6% yield, 95% purity) as a white solid. MS (M-OH): 1222.4 ; DMSO 400 MHz 5 = 0.81 - 0.91 (m, 10 H) 0.92 - 1.11 (m, 6 H) 1.12 - 1.39 (m, 17 H) 1.42 (br d, J=10.8 Hz, 4 H) 1.73 - 1.89 (m, 4 H) 2.06 - 2.10 (m, 2 H) 2.16 - 2.26 (m, 2 H) 3.53 - 3.61 (m, 1 H) 3.69 - 3.82 (m, 3 H) 3.94 - 4.06 (m, 2 H) 4.07 - 4.28 (m, 6 H) 4.30 - 4.42 (m, 4 H) 4.78 - 5.14 (m, 9 H) 6.73 (br s, 1 H) 7.17 (d, J=8.4 Hz, 2 H) 7.27 - 7.31 (m, 3 H) 7.36 (d, J=8.4 Hz, 1 H) 7.45 (br d, J=9.2 Hz, 1 H) 7.55 - 7.62 (m, 1 H) 7.88 (d, J=0.8 Hz, 1 H) 8.06 (br d, J=8.8 Hz, 1 H) 8.19 (br d, J=8.0 Hz, 1 H) 8.29 (br d, J=8.4 Hz, 1 H) 9.22 (br s, 1 H) 10.24 (br s, 1 H).

[0503] Example 84:

[0504] To a solution of pneumocandin bO (2.5 g, 2.4 mmol) in DCM (40 mL) was added Et3SiH (145 mmol, 23 mL) in DCM (40 mL) drop-wise at 15°C under N2atmosphere. Then TFA (145 mmol, 10.7 mL) in DCM (20 mL) was added drop-wise to the above mixture at - 20°C. The reaction mixture was warmed and stirred at 15°C for 3 hours. The reaction mixture was concentrated under reduced pressure at 30°C. The residue was purified by prep- HPLC (HC1 condition: Phenomenex luna C18 (250 x 70mm x 15um);mobile phase: [water(HCl)-ACN];B%: 38%-68%,20min) to give Intermediate 1 (1.45 g, 1.40 mmol, 59.8% yield) as a white solid.

[0505] To a solution of Intermediate 1 (2.92 g, 2.83 mmol) in THF (40 mL) and DMF (5 mL) was added Cs2CO3(1.84 g, 5.66 mmol) in one portion at -10°C under N2atmosphere. Then l,l,l-trifluoro-N-phenyl-N-(trifluoromethylsulfonyl)methanesulfonamide (1.52 g, 4.24 mmol) was added to the reaction mixture at -10°C. The reaction mixture was stirred at -10 °C for 16 hours. The reaction mixture was quenched with H2O (100 mL) and the aqueous phase was extracted with ethyl acetate (80 mL x 3). The combined organic phases were washed with brine (30 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (HC1 condition: Phenomenex luna C18 (250 x 70mm x 15um);mobile phase: [water(HCl)-ACN];B%: 40%- 70%,20min) to give Intermediate 2 (2.7 g, 2.32 mmol, 81.9% yield) as a white solid.

[0506] To a solution of Intermediate 2 (2.6 g, 2.23 mmol) in dioxane (30 mL) was added 4,4,5,5-tetramethyl-2-(4,4,5,5-tetramethyl-l,3,2-dioxaborolan-2-yl)-l,3,2-dioxaborolane (737 mg, 2.90 mmol), KO Ac (547 mg, 5.58 mmol) and (1,1'- Bis(diphenylphosphino)ferrocene)palladium(II) dichloride (Pd(dppf)Cl2).CH2C12 (364 mg, 446 umol) in one portion at 20°C under N2atmosphere. The reaction mixture was degassed and purged with N23 times. Then the reaction mixture was heated and stirred at 110°C for 1.5 hours under N2atmosphere. The reaction mixture was quenched with H2O (80 mL) and the aqueous phase was extracted with ethyl acetate (70 mL x 3). The combined organic phases were washed with brine (30 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (HC1 condition: Phenomenex luna Cl 8 (250 x 70mm x 15pm);mobile phase: [water(HCl)- ACN];B%: 50%-80%, 20 minutes) to give Intermediate 3 (600 mg crude) as a white solid.

[0507] To a solution of Intermediate 3 (600 mg, 525 umol) in acetone (6 mL) and H2O (3 mL) was added NaIO4(337 mg, 1.57 mmol) and NH4OAc (121 mg, 1.57 mmol) in one portion at 20°C. The reaction mixture was heated to 40°C and stirred for 5 hours. After cooling to room temperature, the reaction mixture was quenched with H2O (30 mL) and the aqueous phase was extracted with ethyl acetate (50 mL x 3). The combined organic phases were washed with brine (15 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to dryness. The residue was purified by prep-HPLC (HC1 condition: Phenomenex Luna 80 x 30mm x 3pm;mobile phase: [water(HCl)-ACN];B%: 35%-60%, 8 minutes) to give Example 84 (320 mg, 302 pmol, 57.4% yield) as a white solid. MS (M+H): 1061.6 ; Hl NMR: DMS0400 MHz 5 ppm 0.78 - 0.85 (m, 11 H) 0.86 - 0.93 (m, 1 H) 0.96 - 1.11 (m, 6 H) 1.15 - 1.33 (m, 16 H) 1.34 - 1.50 (m, 5 H) 1.62 - 1.74 (m, 1 H) 1.81 - 1.96 (m, 3 H) 1.99 - 2.15 (m, 4 H) 2.16 - 2.28 (m, 2 H) 2.42 (br d, .7=4,4 Hz, 1 H) 2.53 - 2.66 (m, 2 H) 2.90 (br d, J=14.0 Hz, 1 H) 3.40 - 3.49 (m, 1 H) 3.54 - 3.62 (m, 1 H) 3.71 (br d, J=10.0 Hz, 1 H) 3.79 - 3.93 (m, 3 H) 4.13 (s, 2 H) 4.20 - 4.28 (m, 4 H) 4.35 - 4.42 (m, 3 H) 4.75 (br dd, J=8.0, 2.4 Hz, 1 H) 4.90 (br dd, J=8.4, 3.6 Hz, 1 H) 6.77 (br s, 1 H) 7.14 (br d, .7=7,6 Hz, 2 H) 7.22 (br s, 1 H) 7.36 (br d, J=8.8 Hz, 1 H) 7.57 (br dd, J=7.2, 1.6 Hz, 1 H) 7.68 (br d, J=7.6 Hz, 3 H) 8.07 (br d, J=8.0 Hz, 1 H) 8.21 (br s, 1 H). Example 85:

[0508] To a solution of Example 86 Intermediate 3 (150 mg, 145 pmol, 1.00 eq) in DMF (1 mL) were added 4-Aminophenylboronic acid (39 mg, 290 pmol, 2.00 eq), EDCI (55 mg, 290 pmol, 2.00 eq) and Py (46 pL, 580 pmol, 4.00 eq) at 25°C. The reaction mixture was stirred at 25°C for 1 hour, and was then quenched by addition of H2O (5 mL) and brine (2 mL x 2) at 25°C, a white solid was precipitated. The mixture was filtered and the filter cake was washed with H2O (3 mL x 3). The filter cake was dried in vacuum to give crude product, which was purified by prep-HPLC ( neutral condition; column: Waters Xbridge Prep OBD Ci8150 x 40mm x 10pm ; mobile phase: [H2O(10mM NH4HCO3)-CAN] ; gradient:40%-70% B over 8.0 min) to give Example 85 (82.2 mg, 56.9 pmol, 47.4% yield, 99.3% purity) as a white solid. MS (M + H): 1153.5 ; ’H NMR: DMSO 400MHz 5 = ppm 9.68 (s, 1H), 9.16 (s, 1H), 8.48 (d, J = 8.0 Hz, 1H), 8.29 (d, J = 8.0 Hz, 1H), 7.84 (s, 2H), 7.75 (d, J = 7.6 Hz, 1H), 7.69 (d, J = 8.4 Hz, 2H), 7.57 - 7.54 (m, 3H), 7.32 (d, J = 8.4 Hz, 1H), 6.96 (d, J = 8.4 Hz, 2H), 6.66 (d, J = 8.4 Hz, 2H), 5.26 (d, J = 4.8 Hz, 1H), 5.16 - 5.15 (m, 2H), 5.12 - 5.11 (m, 1H), 4.98 - 4.87 (m, 2H), 4.80 (d, J = 6.0 Hz, 2H), 4.43 - 4.25 (m, 5H), 4.24 - 4.08 (m, 4H), 4.03 - 3.86 (m, 2H), 3.83 - 3.68 (m, 2H), 3.66 - 3.49 (m, 2H), 3.17 (s, 1H), 2.87 (d, J = 14.8 Hz, 2H), 2.48 - 2.38 (m, 3H), 2.28 - 2.20 (m, 1H), 2.20 - 2.09 (m, 2H), 2.09 - 1.98 (m, 1H), 1.97 - 1.70 (m, 4H), 1.52 - 1.34 (m, 4H), 1.34 - 1.13 (m, 14H), 1.09 - 0.96 (m, 5H), 0.91 - 0.85 (m, 1H), 0.84 - 0.78 (m, 9H).

[0509] Example 86:

[0510] To a solution of Et3SiH (47.8 mL, 300 mmol, 8.00 eq) in TFA (251 mL, 3.38 mol, 90.0 eq) was added pneumocandin bO (40.0 g, 37.5 mmol, 1.00 eq) at 0°C under N2. The reaction mixture was stirred at 0°C for 6 hours. HPLC showed the starting material was consumed completely. The mixture was poured into a solution of K2CO3(280 g) in H2O (600 mL) at 0°C and stirred for 0.5 hour. The reaction mixture was filtered, the filter cake was washed with water (300 mL x 2) and dried in vacuum to give Intermediate 1 (4.00 g, 3.82 mmol, 10.6% yield) as a white solid, which was used to next step straightly and without further purified.

[0511] To a solution of Intermediate 1 (37.0 g, 35.8 mmol, 1.00 eq) in MeOH (370 mL) was added toluenesulfonic acid (TsOH) (12.3 g, 71.6 mmol, 2.00 eq) drop-wise at 25°C. The resulting mixture was heated to 49°C and stirred for 120 hours, and then cooled to room temperature, and quenched by addition H2O (200 mL) at 25°C, and then diluted with brine (30 mL). The reaction mixture was filtered, the filter cake was washed with water (50 mL x 2) and dried in vacuum. The residue was purified by prep-HPLC (TFA condition; column: Phenomenex luna Ci8250 x 150mm x 15um; mobile phase: [H2O (0.01%TFA)-ACN] ; gradient: 50%-75% B over 20.0 min) to give Intermediate 2 (4.00 g, 3.82 mmol, 10.6% yield) as a white solid.

[0512] To a solution of Intermediate 2 (3.00 g, 2.86 mmol, 1.00 eq) in MeOH (25 mL) and H2O (5 mL) was added LiOH (1.20 g, 28.6 mmol, 10.0 eq) at 25°C. The reaction mixture was stirred at 25°C for 1 hour, and was then quenched by addition of H2O (50 mL) at 25°C, and diluted with brine (20 mL). The mixture was acidified with aqueous HC1 (2 N) till pH = 4. And then the mixture was filtered and the filter cake was washed with H2O (20 mL x 3). The filter cake was dried in vacuum to give Intermediate 3 (3.5 g, crude) as a white solid, which was used to next step straightly and without further purified.

[0513] To a solution of Intermediate 3 (150 mg, 145 pmol, 1.00 eq) in DMF (1 mL) were added B-(2-Aminophenyl)boronic acid (39 mg, 290 pmol, 2.00 eq), EDCI (55 mg, 290 pmol, 2.00 eq) and Py (47 pL, 580 pmol, 4.00 eq) at 25°C. The reaction mixture was stirred at 25°C for 1 hour, and was then quenched by addition of H2O (5 mL) and brine (2 mL x 2) at 25°C, and some solid was precipitated. The mixture was filtered and the filter cake was washed with H2O (3 mL x 3). The filter cake was dried in vacuum to give crude product which was purified by prep-HPLC ( neutral condition; column: Waters Xbridge Prep OBD Cis 150 x 40mm x 10um;mobile phase: [H2O(10mM NH4HCO3)-ACN] ; gradient:40%-70% B over 8.0 min) to give Example 86 (33.2 mg, 28.4 pmol, 19.6% yield, 98.8% purity) as a white solid. MS (M - 2 H2O + H): 1117.5 ; *H NMR: DMSO 400MHz 5 = ppm 9.17 - 9.08 (m, 1H), 9.05 (s, 1H), 8.80 - 8.71 (m, 1H), 8.17 - 8.10 (m, 1H), 7.99 - 7.82 (m, 1H), 7.76 -

[0514] 7.53 (m, 1H), 7.48 - 6.91 (m, 5H), 6.81 - 6.40 (m, 4H), 5.61 - 5.88 (m, 1H), 5.22 - 5.14 (m, 2H), 5.13 (d, J = 2.4 Hz, 1H), 5.01 - 4.92 (m, 1H), 4.89 - 4.70 (m, 3H), 4.62 - 4.59 (m, 1H),

[0515] 4.54 - 4.46 (m, 1H), 4.42 - 4.37 (m, 2H), 4.32 - 4.19 (m, 3H), 4.14 - 4.08 (m, 1H), 3.98 - 3.94 (m, 1H), 3.87 - 3.60 (m, 4H), 3.55 - 3.46 (m, 1H), 3.27 - 3.11 (m, 2H), 3.08 - 2.98 (m, 1H), 2.90 - 2.72 (m, 1H), 2.42 - 2.22 (m, 3H), 2.19 - 2.08 (m, 2H), 1.95 - 1.76 (m, 3H), 1.67 - 1.55 (m, 1H), 1.51 - 1.33 (m, 4H), 1.31 - 1.14 (m, 12H), 1.13 - 1.00 (m, 4H), 0.98 - 0.94 (m, 1H), 0.93 - 0.86 (m, 1H), 0.84 - 0.73 (m, 9H). Example 87:

[0516] To a solution of Example 86 Intermediate 3 (90 mg, 87.0 pmol, 1.00 eq) in DMF (1 mL) was added 3-Aminophenylboronic acid (23 mg, 174 pmol, 2.00 eq), l-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDCI) (33 mg, 174 pmol, 2.00 eq) and Py (28 pL, 348 pmol, 4.00 eq) at 25°C. The reaction mixture was stirred at 25°C for 1 hour and then quenched by addition of H2O (5 mL) and brine (2 mL x 2) at 25 °C, and a white solid was precipitated. The mixture was filtered and the filter cake was washed with H2O (3 mL x 3). The filter cake was dried in vacuum to give crude product, which was purified by prep-HPLC (neutral condition; column: Waters Xbridge Prep OBD Ci8 150 x 40mm x lOum ; mobile phase: [H2O(10mM NH4HC03)-ACN];gradient:40%-70% B over 8.0 minutes) to give Example 87 (31 mg, 26.8 pmol, 30.8% yield) as a white solid. MS (M - H2O + H):l 135.5 ; ’H NMR: DMSO 400MHz 5 = ppm 9.66 (s, 1H), 9.15 (s, 1H), 8.45 (d, J = 8.4 Hz, 1H), 8.25 (d, J = 8.4 Hz, 1H), 7.92 (s, 1H), 7.87 (s, 1H), 7.74 - 7.70 (m, 2H), 7.48 - 7.52 (m, 1H), 7.45 (d, J = 7.4 Hz, 1H), 7.33 (d, J = 7.6 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 6.97 (d, J = 8.4 Hz, 2H), 6.66 (d, J = 8.4 Hz, 2H), 5.26 (d, J = 4.8 Hz, 1H), 5.15 (d, J = 3.2 Hz, 1H), 4.97 - 4.96 (m, 1H), 4.92 - 4.91 (m, 2H), 4.83-4.78 (m, 2H), 4.37 - 4.26 (m, 5H), 4.23 - 4.13 (m, 4H), 3.98 - 3.97 (m, 1H), 3.91 - 3.85 (m, 1H), 3.84-.3.79 (m, 1H), 3.73 (d, J = 10.4 Hz, 1H), 3.61 - 3.57 (m, 1H), 3.56 - 3.50 (m, 1H), 3.21 (s, 1H), 2.89 - 2.81 (m, 2H), 2.44 - 2.40 (m, 3H), 2.25 - 2.22 (m, 1H), 2.18 - 2.14 (m, 2H), 2.06 - 2.03 (m, 1H), 1.88 - 1.78 (m, 4H), 1.42 - 1.31 (m, 4H), 1.30 - 1.11 (m, 14H), 1.09 - 1.02 (m, 5H), 1.00 - 0.89 (m, 1H), 0.88 - 0.86 (m, 9H).

[0517] Example 88 and Example 168:

[0518] To a solution of Example 91 (180 mg, 149 pmol, 1 eq, TFA) and 3- (dimethylamino)propanal (75 mg, 351 pmol, 2.35 eq, TFA) in MeOH (2 mL) were added NaHCO3(125 mg, 1.49 mmol, 10 eq) and NaBH3CN (46.0 mg, 747 pmol, 5 eq) in portions at 25°C under N2. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was quenched by H2O (6 mL) at 0°C, yellow solid was precipitated, the mixture was filtered and the cake was washed by water (2 mL x 2). The cake was purified by prep-HPLC (column: 3_Phenomenex Luna Ci8 75 x 30mm x 3um; mobile phase: [H2O(0.1% TFA)- ACN]; gradient: 20%-50% B over 8.0 min) to give Example 168 and Example 88. Example 168 (9.40 mg, 7.95 pmol, 5.32% yield, 99.4% purity) as a white solid. MS: [M+H]+1175.7 ; ’H NMR: MeOD 400 MHz 5 = ppm 7.71 - 7.66 (m, 1H), 7.58 - 7.52 (m, 2H), 7.26 - 7.19 (m, 2H), 5.12 - 5.05 (m, 2H), 4.66 - 4.50 (m, 6H), 4.50 - 4.34 (m, 5H), 4.05 - 3.82 (m, 6H), 3.28 - 3.11 (m, 6H), 2.98 - 2.88 (m, 9H), 2.78 - 2.67 (m, 4H), 2.52 - 2.41 (m, 3H), 2.34 - 2.22 (m, 5H), 2.19 - 1.97 (m, 6H), 1.64 - 1.58 (m, 3H), 1.54 - 1.38 (m, 4H), 1.37 - 1.23 (m, 15H), 1.19 - 1.04 (m, 6H), 0.98 - 0.87 (m, 11H).

[0519] Example 88 (44.2 mg, 35.0 pmol, 23.4% yield, 99.8% purity) as a white solid. MS: [M+H]+1260.8 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.59 - 8.50 (m, 1H), 7.74 - 7.67 (m, 1H), 7.56 - 7.52 (m, 2H), 7.24 - 7.18 (m, 2H), 7.03 - 7.01 (m, 1H), 6.71 - 6.69 (m, 1H), 5.11 - 5.04 (m, 2H), 4.73 - 4.50 (m, 6H), 4.38 - 4.23 (m, 3H), 4.04 - 4.00 (m, 1H), 3.94 - 3.78 (m, 4H), 3.24 - 3.11 (m, 5H), 2.93 (s, 12H), 2.89 - 2.79 (m, 2H), 2.76 - 2.21 (m, 12H), 2.11 - 1.93 (m, 7H), 1.66 - 1.49 (m, 3H), 1.49 - 1.20 (m, 15H), 1.16 - 1.04 (m, 5H), 0.96 - 0.85 (m, 9H).

[0520] Example 89:

[0521] To a mixture of Example 123 Intermediate 4 (200 mg, 185 pmol, 1 eq) in TFA (2 mL) was added triethylsilane (TESH) (64.7 mg, 556 pmol, 3 eq) drop-wise at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was adjusted to pH =5~6 with K2CO3aqueous (15%, ~10 mL) and white solid precipitated, the mixture was filtered under reduce pressure to give a cake. The filter cake was washed with H2O (3 mL x 2) and purified by prep-HPLC (TFA condition, column: Welch Ultimate Ci8120 x 30mm x 5pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 40%-70% B over 8.0 minutes) to give Example 89 (70.0 mg, 59.5 pmol, 32.1% yield, TFA) as a white solid.

[0522] MS (M+H+): 1062.6 ; ’H NMR: (400 MHz, DMSO- d6) 5 9.16 (s, 1H), 8.71 (d, J= 8.8 Hz, 1H), 8.21 (d, J= 8.0 Hz, 1H), 8.08 (d, J= 7.6 Hz, 1H), 7.62 (br s, 2H), 7.42 (d, J= 10.0 Hz, 1H), 7.34 (br s, 1H), 7.22 (d, J= 8.8 Hz, 1H), 6.94 (d, J= 8.4 Hz, 2H), 6.70 (br s, 1H), 6.64 (d, J= 8.4 Hz, 2H), 5.23 - 5.10 (m, 2H), 4.99 - 4.88 (m, 3H), 4.86 - 4.68 (m, 3H), 4.44 - 4.36 (m, 3H), 4.36 - 4.30 (m, 1H), 4.23 - 4.19 (m, 2H), 4.15 (br s, 1H), 4.10 - 3.97 (m, 2H), 3.88 (d, J= 6.8 Hz, 2H), 3.84 - 3.77 (m, 1H), 3.70 (d, J= 10.4 Hz, 1H), 3.64 - 3.57 (m, 1H), 2.93 - 2.82 (m, 2H), 2.58 - 2.53 (m, 1H), 2.47 - 2.43 (m, 1H), 2.25 - 2.17 (m, 2H), 2.13 - 2.04 (m, 3H), 2.02 - 1.94 (m, 1H), 1.92 - 1.79 (m, 3H), 1.47 - 1.35 (m, 4H), 1.34 - 1.16 (m, 14H), 1.11 - 0.99 (m, 5H), 0.93 - 0.80 (m, 11H).

[0523] Example 90:

[0524] To a mixture of Example 91 (150 mg, 125 pmol, 1 eq, TFA) and 2- (dimethylamino)acetaldehyde hydrochloride (23.1 mg, 187 pmol, 1.5 eq) in MeOH (2.0 mL) was added triethylamine (TEA) (37.8 mg, 374 pmol, 3 eq) in one portion at 20°C, then the reaction mixture was stirred for 0.5 hour. After then NaBH3CN (39.1 mg, 623 pmol, 5 eq) was added to the above mixture in one portion at 20°C. The reaction mixture was stirred at 20°C for 48 hours. The reaction mixture was quenched by sat. NH4C1 (5 mL) and white solid was precipitated, the mixture was filtered under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition) column: Welch Ultimate Ci8(120 x 30 mm, 5 um); mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 35%-65% B over 8.0 min to give Example 90 (41.1 mg, 35.4 pmol, 28.4% yield, TFA) as a white solid. MS (M+H+):

[0525] 1161.6 ; ’H NMR: (400 MHz, DMSO-t / 6): 8 9.83 (br s, 1H), 8.68 (d, J= 7.2 Hz, 1H), 8.26 (d, J= 8.0 Hz, 1H), 8.24 - 8.17 (m, 1H), 7.96 (br s, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.44 (d, J=

[0526] 9.6 Hz, 1H), 7.29 - 7.20 (m, 2H), 7.13 (d, J= 7.6 Hz, 2H), 6.71 (br s, 1H), 5.16 (br s, 1H), 5.01 (br s, 1H), 4.95 - 4.82 (m, 4H), 4.42 (br s, 2H), 4.37 - 4.26 (m, 4H), 4.25 - 4.15 (m, 3H), 4.03 - 3.94 (m, 2H), 3.89 - 3.80 (m, 2H), 3.71 (d, J= 10.4 Hz, 1H), 3.62 (d, J= 8.4 Hz, 1H), 3.09 (br s, 3H), 2.80 (br s, 6H), 2.59 - 2.55 (m, 2H), 2.25 - 2.17 (m, 2H), 2.16 - 2.00 (m, 4H), 1.93 - 1.80 (m, 3H), 1.48 - 1.37 (m, 4H), 1.36 - 1.16 (m, 15H), 1.11 - 1.00 (m, 5H), 0.93 - 0.81 (m, 11H).

[0527] Example 91:

[0528] To a solution of Example 123 Intermediate 3A (100 mg, 93.0 pmol, 1 eq) in TFA (1 mL) was added TESH (108 mg, 930 pmol, 148 pL, 10 eq) in one portion at 0°C. The reaction mixture was warmed to 25°C and stirred for 1 hour. Desired peak was observed on HPLC. Brine 10 ml was added to the yellow solution and the mixture was extracted with EtOAc (10 ml x 3). The combined layers were washed by brine 10 ml, dried over Na2SO4, filtered and concentrated to give yellow solid which was purified by prep-HPLC(column: 3_Phenomenex Luna C18 75*30mm*3pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 30%-60% B over 8.0 minutes). Intermediate 1 (25.0 mg, 25.3% yield) was obtained as a white solid.

[0529] To a mixture of Intermediate 1 (2.50 g, 2.36 mmol, 1 eq) and K2CO3(1.96 g, 14.2 mmol, 6 eq) in THF (30 mL) and DMF (10 mL) was added Tf2NPh (5.06 g, 14.2 mmol, 6 eq) in one portion at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was quenched with H2O (90 mL) and light yellow solid precipitated, the mixture was filtered under reduce pressure to give a cake. The filter cake was washed with MeCN (50 mL x 2) to give crude Intermediate 2 (2.80 g, -80% HPLC purity) as a light-yellow solid.

[0530] To a mixture of Intermediate 2 (2.80 g, 2.35 mmol, 1 eq) and B2neop2(562 mg, 2.49 mmol, 3 eq) in DMA (28 mL) were added KOAc (461 mg, 4.70 mmol, 2 eq) and Mesylate[(di(l- adamantyl)-n-butylphosphine)-2-(2 '-amino- 1, 1 '-biphenyl)]palladium(II), [(Di(l-adamantyl)- butylphosphine)-2-(2 '-amino- 1, 1 '-biphenyl)]palladium(II) methanesulfonate (cataCXiumAPdG3) (171 mg, 235 pmol, 0.1 eq) in one portion at 25°C under N2atmosphere, the reaction mixture was degassed and purged with N2for 3 times. The reaction mixture was heated to 80°C and stirred for 10 minutes under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with brine 50 mL and off-white solid was precipitated, the mixture was filtered under reduce pressure to give a residue. The residue was washed with MTBE: EtOAc =1 : 1 (30 mL x 2) to give Intermediate 3 (2.50 g, -70% HPLC purity) as an off white solid.

[0531] To a mixture of Intermediate 3 (2.50 g, 2.16 pmol, 1 eq) and CoCl2(675 mg, 5.20 mmol, 2 eq) in MeOH (30 mL) was added NaBH4(3.98 g, 105 mmol, 40.5 eq) in portions at 0°C under N2atmosphere. The reaction mixture was stirred at 0°C for 1 hour. LCMS showed the starting material was consumed completely and desired MS was observed. The reaction mixture was adjusted to pH = 4-5 with HC1 (2N) and freeze drying to give a residue. The residue was purified by prep-HPLC (TFA condition, column: Phenomenex luna Ci8250 x 70mm x 15pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 25%-55% B over 20.0 minutes) to give Example 91 (500 mg, 415 pmol, 16.0% yield, TFA) as a white solid. MS (M+H+): 1090.7 ; Hl NMR: (400 MHz, DMSO-t / 6): 8 8.72 (d, J= 8.4 Hz, 1H), 8.21 (d, J= 8.4 Hz, 1H), 8.09 (d, J= 7.2 Hz, 1H), 7.96 (br s, 2H), 7.68 (d, J= 7.6 Hz, 2H), 7.64 (br s, 2H), 7.45 (d, J= 10.0 Hz, 1H), 7.34 (br s, 1H), 7.24 (d, J= 8.4 Hz, 1H), 7.13 (d, J= 7.6 Hz, 2H), 6.71 (br s, 1H), 5.31 - 5.08 (m, 2H), 4.97 (br s, 1H), 4.93 - 4.89 (m, 1H), 4.86 - 4.82 (m, 1H), 4.74 (br s, 1H), 4.43 - 4.30 (m, 4H), 4.28 - 4.20 (m, 3H), 4.19 - 4.13 (m, 2H), 4.04 - 3.97 (m, 1H), 3.89 (d, J = 6.4 Hz, 2H), 3.84 - 3.78 (m, 1H), 3.70 (d, J= 11.2 Hz, 1H), 3.64 - 3.56 (m, 2H), 2.88 (br s, 2H), 2.58 (br d, J= 4.0 Hz, 2H), 2.26 - 2.17 (m, 2H), 2.14 - 2.06 (m, 3H), 2.03 - 1.95 (m, 1H), 1.93 - 1.80 (m, 3H), 1.47 - 1.35 (m, 4H), 1.35 - 1.15 (m, 15H), 1.09 - 0.99 (m, 5H), 0.93 - 0.81 (m, 11H). Example 92:

[0532] To a mixture of Example 91 (100 mg, 83.1 pmol, 1 eq, TFA) and dimethylglycine (17.1 mg, 166 pmol, 2 eq) in DMF (1 mL) were added l-Ethyl-3-(3- dimethylaminopropyl)carbodiimide (EDCI) (31.8 mg, 166 pmol, 2eq) and Pyridine (52.6 mg, 664 pmol, 8 eq) in one portion at 20°C. The reaction mixture was stirred at 20°C for 3 hours. The reaction mixture was quenched by H2O (5 mL) and white solid was precipitated; the mixture was filtered under reduce pressure to give a cake. The cake was purified by prep- HPLC (TFA condition, column: Welch Ultimate Ci8120 x 30mm x 5pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 30%-60% B over 8.0 minutes) to give Example 92 (40.6 mg, 31.5 pmol, 37.9% yield, TFA) as a white solid. MS (M+H+): 1175.6 ;1H NMR: (400 MHz, DMSO-d6) 8 9.63 (br s, 1H), 8.62 (d, J= 8.0 Hz, 1H), 8.42 (br s, 1H), 8.20 (d, J= 8.0 Hz, 1H), 7.95 (br s, 2H), 7.79 (d, J= 8.8 Hz, 1H), 7.68 (d, J= 7.6 Hz, 2H), 7.48 (d, J= 9.6 Hz, 1H), 7.36 (br s, 1H), 7.23 (d, J= 8.0 Hz, 1H), 7.13 (d, J= 7.6 Hz, 2H), 6.69 (br s, 1H), 5.16 (br s, 2H), 4.97 - 4.81 (m, 4H), 4.77 - 4.62 (m, 2H), 4.41 (br s, 2H), 4.37 - 4.32 (m, 1H), 4.25 - 4.15 (m, 5H), 4.02 (br s, 1H), 3.93 - 3.78 (m, 3H), 3.73 - 3.67 (m, 2H), 3.64 - 3.57 (m, 1H), 3.26 (br s, 1H), 3.20 - 3.13 (m, 1H), 2.77 (br s, 6H), 2.57 - 2.53 (m, 2H), 2.26 - 2.16 (m, 2H), 2.11 - 2.01 (m, 3H), 1.91 - 1.82 (m, 3H), 1.47 - 1.35 (m, 4H), 1.34 - 1.14 (m, 15H), 1.10 - 0.98 (m, 5H), 0.93 - 0.81 (m, 11H).

[0533] Example 93:

[0534] To a mixture of Example 123 Intermediate 3B (5.00 g, 4.65 mmol, 1 eq) and K2CO2(3.86 g, 27.9 mmol, 6 eq) in THF (45 mL) and DMF (15 mL) was added N-Phenyl- bis(trifluoromethanesulfonimide) (Tf2NPh) (9.98 g, 27.9 mmol, 6 eq) in one portion at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was quenched with H2O (60 mL) and white solid precipitated, which was filtered under reduced pressure to get the filter cake. The filter cake was washed with acetonitrile (MeCN) (100 mL x 2) and concentrated to give Intermediate 1(3.70 g, crude) as a white solid.

[0535] To a mixture of Intermediate 1 (1.00 g, 829 pmol, 1 eq) and 5,5,5',5'-Tetramethyl- 2,2'-bi-l,3,2-dioxaborinane (Bis(neopentyl glycolato)diboron, B2neop2) (562 mg, 2.49 mmol, 3 eq) in dimethylacetamide (DMA) (10 mL) were added KO Ac (163 mg, 1.66 mmol, 2 eq) and cataCXiumAPdG3 (60.4 mg, 82.9 pmol, 0.10 eq) in one portion under N2atmosphere, the reaction mixture was degassed and purged with N23 times. The reaction mixture was heated to 80°C and stirred for 10 minutes under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with brine 30 mL and off white solid precipitated, which was filtered under reduce pressure to give filter cake. The filter cake was washed with methyl-tert-butyl ether (MTBE): EtOAc =1 : 1 (30 mL x 2) to give the mixture of Intermediate 2a and Intermediate 2b (900 mg, crude) as an off white solid.

[0536] To a mixture of Intermediate 2a and Intermediate 2b (900 mg, 769 pmol, 1 eq) in THF (10.0 mL) were added CoCl2(212 mg, 1.63 mmol, 2 eq) and NaBH4(738 mg, 19.5 mmol, 25.4 eq) in portions at 0°C under N2atmosphere. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was adjusted to pH = 4~5 with HC1 (2N) and freeze- dryed to give a residue. The residue was purified by prep-HPLC (TFA condition, column: Welch Xtimate Ci8250 x 70mm # 10pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient:25%-65% B over 20.0 minutes) to give Intermediate 3a (240 mg, 197 pmol, 25.6% yield, TFA) as a white solid. MS (M+H): 1106.5 ;1H NMR: DMSO-t / 6400 MHz 5 = ppm 8.03 (br s, 2H), 7.85 - 7.77 (m, 1H), 7.72 (d, J= 8.0 Hz, 2H), 7.69 - 7.49 (m, 5H), 7.45 - 7.36 (m, 1H), 7.34 - 7.27 (m, 1H), 7.21 (d, J= 7.6 Hz, 2H), 7.04 - 6.82 (m, 2H), 5.60 - 5.12 (m, 5H), 5.10 - 4.95 (m, 1H), 4.92 (d, J= 10.0 Hz, 1H), 4.80 - 4.64 (m, 1H), 4.57 (br s, 1H), 4.47 - 4.27 (m, 6H), 4.21 - 4.10 (m, 2H), 4.08 - 4.03 (m, 1H), 3.95 (br s, 1H), 3.77 - 3.69 (m, 2H), 3.62 (br s, 2H), 3.09 - 2.98 (m, 1H), 2.88 - 2.76 (m, 1H), 2.35 - 2.27 (m, 1H), 2.24 - 2.05 (m, 5H), 1.87 - 1.69 (m, 3H), 1.46 - 1.35 (m, 4H), 1.34 - 1.11 (m, 17H), 1.10 - 0.95 (m, 3H), 0.93 - 0.80 (m, 11H).

[0537] To a mixture of Intermediate 3a (200 mg, 166 pmol, 1 eq, TFA) and dimethylglycine (34.2 mg, 332 pmol, 2 eq) in DMF (2 mL) were added EDCI (63.6 mg, 332 pmol, 2eq) and Pyridine (105 mg, 1.33 mmol, 8 eq) in one portion at 20°C. The reaction mixture was stirred at 20°C for 3 hours. The reaction mixture was quenched by H2O 6 mL and white solid was precipitated; the mixture was filtered under reduce pressure to give the filter cake. The filter cake was washed with H2O (2 mL x 2) and purified by prep-HPLC (TFA condition, column: Welch Ultimate Ci8120 x 30mm x 5pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 35%-65% B over 8.0 minutes) to give Example 93 (50.9 mg, 42.7 pmol, 25.7% yield, TFA) as a white solid. MS (M+H+): 1191.6 ; ’H NMR: (400 MHz, DMSO-t / 6) 8 9.67 (br s, 1H), 8.37 (br s, 1H), 8.05 (br s, 1H), 7.86 - 7.78 (m, 1H), 7.72 (d, J = 7.6 Hz, 2H), 7.63 - 7.51 (m, 2H), 7.34 - 7.26 (m, 1H), 7.21 (d, J= 7.6 Hz, 2H), 6.98 - 6.81 (m, 2H), 5.41 - 5.12 (m, 4H), 4.99 - 4.85 (m, 2H), 4.63 - 4.54 (m, 1H), 4.42 - 4.34 (m, 3H), 4.31 (d, J= 7.6 Hz, 1H), 4.25 - 4.11 (m, 3H), 4.02 (br s, 1H), 3.94 (br s, 1H), 3.84 - 3.65 (m, 5H), 3.60 - 3.46 (m, 3H), 3.14 - 3.02 (m, 1H), 2.79 (s, 6H), 2.32 - 2.04 (m, 6H), 1.91 - 1.60 (m, 4H), 1.54 - 1.35 (m, 5H), 1.34 - 1.12 (m, 17H), 1.09 - 0.95 (m, 3H), 0.92 - 0.80 (m, 11H).

[0538] Example 94:

[0539] To a solution of Example 123 Intermediate 3A (7.00 g, 6.51 mmol, 1 eq) and NaHCO3(2.69 g, 32.5 mmol, 905 pL, 5 eq) in DMF (12.5 mL) and THF (37.5 mL) was added Tf2NPh (11.6 g, 32.5 mmol, 5 eq) in one portion at 25°C. The reaction mixture was stirred at 20°C for 1 hour. Parallel reactions were combined for work-up. The reaction mixture was quenched by H2O (30 mL) at 25°C. The reaction mixture was filtered, the filter cake was collected and dried in vacuum. The crude product was purified by reversed-phase HPLC (0.1% TFA condition) to give Intermediate 1 (4.50 g, 3.73 mmol, 57.0% yield) as a white solid.

[0540] A mixture of Intermediate 1 (2.50 g, 2.07 mmol, 1 eq), B2neop2(1.40 g, 6.22 mmol, 3 eq), cataCXiumAPdG3 (151 mg, 207 pmol, 0.1 eq) in DMA (25.0 mL) was degassed and purged with N2for 3 times. The reaction mixture was added KO Ac (813 mg, 8.29 mmol, 4 eq) in one portion at 20°C under N2, the reaction mixture was degassed and purged with N2for 3 times at 20°C. Then the reaction mixture was heated to 80°C and stirred for 10 minutes under N2atmosphere. After cooling to room temperature, the reaction mixture was quenched with sat. brine (100 mL). The mixture was filtered and the filter cake was washed with MTBE: EtOAc =1 : 1 (100 mL x 2) to give the mixture (3.50 g, crude) of the two stereoisomers Intermediate 2a and Intermediate 2b as an off white solid.

[0541] To a mixture of Intermediate 2a and Intermediate 2b (3.20 g, 2.73 mmol, 1 eq) and CoCl2(710 mg, 5.47 mmol, 2 eq) in THF (30 mL) was added NaBH4(2.49 g, 65.8 mmol, 24.0 eq) in portions at 0°C under N2atmosphere. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was adjusted to pH =4~5 with HC1 (2N), filtered and the collected filter cake was concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna Ci8(250 * 70mm, 15 pm); mobile phase: [H2O (0.1%TFA)-ACN]; gradient:25%-55% B over 20.0 minutes) to give pure isomer Intermediate 3a (330 mg, 298 pmol, 10.9% yield, TFA) as a white solid.

[0542] To a mixture of Intermediate 3a (120 mg, 98.4 pmol, 1 eq, TFA) and 2- (dimethylamino)acetaldehyde hydrochloride (18.2 mg, 148 pmol, 1.5 eq, HC1) in MeOH (2 mL) was added TEA (29.9 mg, 295 pmol, 3 eq) in one portion at 20°C, the reaction mixture was stirred for 0.5 hour at 20°C. Then NaBH3CN (30.9 mg, 492 pmol, 5 eq) was added the above reaction mixture in one portion at 20°C. The reaction mixture was stirred at 20°C for 36 hours. The reaction mixture was quenched by sat. NH4C1 (5 mL) at 20°C and white solid precipitated, the mixture was filtered under reduce pressure to give a cake. The filter cake was washed with H2O (2 mL x 2) and purified by prep-HPLC (TFA condition) column: Welch Ultimate Ci8(120 x 30 mm, 5 pm); mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 35%-65% B over 8.0 minutes to give Example 94 (20.0 mg, 17.0 pmol, 17.3% yield, TFA) as a white solid. MS (M+H+): 1177.7 ; ’H NMR: (400 MHz, DMSO-t / 6+ D2O) 5 8.61 (d, J = 7.6 Hz, 1H), 8.51 (d, J= 8.8 Hz, 1H), 7.70 (d, J= 8.0 Hz, 2H), 7.40 (d, J= 9.6 Hz, 1H), 7.18 (d, J= 8.0 Hz, 2H), 7.00 (d, J= 8.8 Hz, 1H), 6.67 (d, J= 8.4 Hz, 1H), 4.93 - 4.79 (m, 2H), 4.40 (br s, 2H), 4.33 - 4.23 (m, 4H), 4.17 - 4.12 (m, 1H), 4.08 - 4.03 (m, 1H), 3.99 - 3.92 (m, 2H), 3.89 - 3.82 (m, 1H), 3.63 - 3.57 (m, 1H), 3.80 - 3.55 (m, 2H), 3.36 - 3.19 (m, 3H), 3.11 - 3.03 (m, 2H), 2.78 (br s, 6H), 2.26 - 2.17 (m, 2H), 2.16 - 1.97 (m, 4H), 1.90 - 1.76 (m, 3H), 1.46 - 1.34 (m, 4H), 1.33 - 1.13 (m, 15H), 1.09 - 0.97 (m, 5H), 0.92 - 0.79 (m, 11H).

[0543] Example 95:

[0544] To a mixture of (3-hydroxypropyl)triphenylphosphonium bromide (20.6 g, 51.5 mmol, 1 eq) in THF (100 mL) was added n-BuLi (2.5 M, 47.4 mL, 2.3 eq) drop-wise at - 10°C under N2. The reaction mixture was stirred at -10°C for 2 hours under N2. Then to the above mixture was added oxazole-5-carbaldehyde (5.00 g, 51.5 mmol, 1 eq) in portions at 0°C. The resulting mixture was stirred for 12 hours under N2. The reaction mixture was quenched by NH4C1 aqueous (300 ml) at 0°C and extracted with EtOAc (200 mL x 3). The combined organic layers were washed with brine (100 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by flash silica gel chromatography (ISCO®; 40 g SepaFlash® Silica Flash Column, Eluent of 0-40% Ethyl acetate / Petroleum ether gradient @ 80 mL / minutes) to give Reagent 1 (5.00 g, 35.9 mmol, 69.7% yield) as yellow gum. MS: [M+H]+140.1.

[0545] To a mixture of Reagent 1 (494 mg, 2.82 mmol, 10 eq) in DMSO (5 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (65.4 mg, 281 pmol, 1 eq) and pneumocandin bO (300 mg, 282 pmol, 1 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 15 hours. The reaction mixture was quenched by water (0.5 mL), after then the resulting solution was purified by prep-HPLC (column: CD09-Phenomenex Gemini Ci8150 x 30mm x 5 pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 35%-65% B over 10.0 min) to give Example 95 (35.0 mg, 28.4 pmol, 10.0% yield, 96.1% purity ) as a white solid. MS (M+H): 1186.5 ; ’H NMR: MeOD 400 MHzS = ppm 9.03 - 9.02 (d, J= 1.6 Hz, 1H), 7.32 (d, J= 1.6 Hz, 1H), 7.22 (d, J= 8.4 Hz, 2H), 6.81 (d, J= 8.4 Hz, 2H), 5.68 (s, 1H), 5.20 (s, 1H), 5.13 (s, 1H), 4.84 (s, 2H), 4.77 - 4.72 (m, 2H), 4.65 (s, 1H), 4.61 - 4.51 (m, 3H), 4.42 (d, J= 9.2 Hz, 1H), 4.30 - 4.21 (m, 1H), 4.18 (d, J= 2.4 Hz, 1H), 4.02 - 3.90 (m, 2H), 3.90 - 3.78 (m, 3H), 3.66 - 3.58 (m, 1H), 3.30 - 3.24 (m, 1H), 3.21 - 3.14 (m, 1H), 2.84 - 2.76 (m, 2H), 2.54 - 2.22 (m, 7H), 2.20 - 2.02 (m, 4H), 1.77 - 1.41 (m, 9H), 1.39 - 1.19 (m, 18H), 0.95 - 0.86 (m, 10H).

[0546] Example 96:

[0547] To a mixture of Example 108 (1.00 g, 880 pmol, 1 eq) in i-PrOH (10.0 mL) and THF (5.0 mL) was added butanal (317 mg, 4.40 mmol, 5 eq) in one portion at 25°C, the reaction mixture was stirred for 1 hour at 25°C. Then AcOH (5.28 mg, 88.0 pmol, 0.1 eq) and NaBH(OAc)3(933 mg, 4.40 mmol, 5 eq) were added to the above mixture at 25°C. The reaction mixture was stirred at 25°C for 3 hours. The reaction mixture was quenched with H2O (30 mL) and extracted with EtOAc(20 mL x 2), the combined organic layer was dried over Na2SO4and concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition) column: Phenomenex luna Ci8(250 x 70mm, 15 um); mobile phase: [H2O (0.1% TFA)-ACN];gradient: 30%-65% B over 8.0 min to give Intermediate 1 (200 mg, 128 pmol, 14.6% yield, TFA) as a white solid.

[0548] To a solution of Intermediate 1 (200 mg, 160 pmol, 1 eq) in TFA (2 mL) was added Et3SiH (801 pmol, 128 pL, 5 eq) drop-wise at 0°C. The reaction mixture was stirred at 0°C for 1 hour. The reaction mixture was adjusted to pH =7~8 with sat.aq. KOAc and concentrated under reduce pressure to give a residue. The residue was purified by prep- HPLC (TFA condition) column: WePure Biotech XP t Ci8(100 x 30mm, 10 pm); mobile phase: [H2O (0.1% TFA)-ACN];gradient: 35%-65% B over 8.0 minutes, to give Example 96 (47.9 mg, 38.9 pmol, 24.3% yield, TFA) as a white solid. MS (M+H): 1232.7 ; ’H NMR: DMSO-t / 6400 MHz 5 = ppm 9.17 (s, 1H), 9.02 (br s, 1H), 8.35 - 8.22 (m, 2H), 8.07 (d, J= 9.2 Hz, 1H), 7.43 (d, J= 9.6 Hz, 1H), 7.29 - 7.20 (m, 2H), 6.94 (d, J= 8.4 Hz, 2H), 6.74 (br s, 1H), 6.64 (d, J= 8.4 Hz, 2H), 5.28 - 5.13 (m, 2H), 5.00 (d, J= 4.4 Hz, 1H), 4.94 - 4.77 (m, 6H), 4.42 - 4.32 (m, 3H), 4.24 - 4.18 (m, 3H), 4.17 - 4.11 (m, 3H), 4.00 - 3.89 (m, 2H), 3.84 - 3.78 (m, 1H), 3.70 (d, J= 10.4 Hz, 1H), 3.65 - 3.57 (m, 1H), 3.45 - 3.40 (m, 1H), 3.06 - 2.98 (m, 6H), 2.26 - 2.05 (m, 5H), 1.91 - 1.75 (m, 4H), 1.64 - 1.38 (m, 13H), 1.36 - 1.15 (m, 20H), 1.09 - 1.00 (m, 5H), 0.91 (t, J= 7.2 Hz, 6H), 0.84 - 0.81 (m, 9H).

[0549] Example 97:

[0550] To a mixture of Example 103 (160 mg, 133 pmol, 1 eq) in TFA(5 ml) was added triethylsilane (TESH) (154 mg, 1.33 mmol, 10 eq) at 0°C. The mixture was stirred at 0°C for 1 hour. The reaction mixture was quenched by addition 40% NaOAc 30 mL at 0°C to pH = 7, filtered and concentrated under reduced pressure to give a residue. The residue was purified by preparative HPLC (CD18-Welch Utimate C18 150*40*7pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 24%-54% B over 10.0 minutes) to afford Example 97 (63.9 mg, 52.5 pmol, 39.5% yield, 97.6% purity) as a white solid. MS (M+H): 1188.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.52 (d, J= 8.4 Hz, 1H), 8.29 - 8.09 (m, 2H), 7.73 (br d, J= 10.0 Hz, 1H), 7.55 (d, J= 8.4 Hz, 1H), 7.02 (d, J= 8.4 Hz, 2H), 6.73 - 6.66 (m, 2H), 5.19 - 5.14 (m, 1H), 5.13 - 5.08 (m, 1H), 5.02 - 4.96 (m, 1H), 4.67 - 4.60 (m, 1H), 4.58 - 4.49 (m, 3H), 4.48 - 4.37 (m, 3H), 4.33 - 4.26 (m, 2H), 4.07 - 3.94 (m, 3H), 3.85 - 3.77 (m, 2H), 3.58 - 3.46 (m, 2H), 3.36 (br d, J= 12.8 Hz, 2H), 2.96 (br t, J= 12.8 Hz, 2H), 2.72 - 2.65 (m, 1H), 2.62 - 2.41 (m, 4H), 2.27 - 2.20 (m, 3H), 2.10 - 1.90 (m, 7H), 1.64 - 1.56 (m, 5H), 1.36 - 1.26 (m, 18H), 1.16 (d, J= 6.4 Hz, 3H), 1.15 - 1.01 (m, 2H), 0.90 - 0.84 (m, 10H).

[0551] Example 98:

[0552] To a solution of Example 104 (90.0 mg, 76.4 pmol, 1 eq, TFA salt) in TFA (1.0 mL) was added triethylsilane (TESH) (88.0 mg, 764 pmol, 10 eq) in one portion at 0°C. The reaction mixture was stirred at 0°C for 2 hours. The reaction mixture was adjusted to pH =7~8 with sat.aq K2CO3at 0°C, yellow solid was precipitated, the mixture was filtered and the cake was washed by water 5 ml x 2. The cake was purified by prep-HPLC (column: Phenomenex Luna Ci8 75 x 30mm x 3pm; mobile phase: [H2O(0.1%TFA)-ACN]; gradient:25%-55% B over 8.0 minutes) to give Example 98 (39.6 mg, 99.2% purity, TFA salt) as a white solid. MS: [M+H]+: 1162.6. ;1H NMR: DMSO 400 MHz 5 = ppm 9.13 - 9.21 (m, 1 H) 8.20 - 8.34 (m, 2 H) 8.16 (d, J= 1.6 Hz, 2 H) 8.08 (d, J= 92 Hz, 1 H) 7.43 (d, J= 9.2 Hz, 1 H) 7.16 - 7.31 (m, 2 H) 6.94 (d, J= 8.4 Hz, 2 H) 6.74 (s, 1 H) 6.64 (d, J= 8.4 Hz, 2 H) 5.24 (d, J= 4.8 Hz, 1 H) 5.16 (d, J= 2.8 Hz, 1 H) 4.99 (d, J= 4.8 Hz, 1 H) 4.82 - 4.96 (m, 4 H) 4.79 (d, J= 6.0 Hz, 2 H) 4.32 - 4.45 (m, 3 H) 4.10 - 4.26 (m, 6 H) 3.95 - 4.03 (m, 1 H) 3.91 (d, J= 6.0 Hz, 1 H) 3.81 (d, J= 8.0 Hz, 1 H) 3.70 (d, J= 10.8 Hz, 1 H) 3.55 - 3.65 (m, 1 H) 3.40 - 3.45 (m, 1 H) 3.26 (m, 1 H) 2.87 (s, 2 H) 2.39 - 2.45 (m, 1 H) 2.13 - 2.26 (m, 2 H) 2.00 - 2.11 (m, 3 H) 1.80 - 1.94 (m, 3 H) 1.69 - 1.79 (m, 1 H) 1.51 - 1.62 (m, 4 H) 1.38 - 1.49 (m, 4 H) 1.14 - 1.34 (m, 20 H) 0.99 - 1.10 (m, 5 H) 0.68 - 0.98 (m, 11 H).

[0553] Example 99:

[0554] To a mixture of (3-hydroxypropyl)triphenylphosphonium bromide (17.7 g, 44.2 mmol, 1 eq) in THF (150 mL) was added n-butyllithium (n-BuLi) (2.5 M, 40.7 mL, 2.3 eq) at 0°C under N2. The reaction mixture was stirred at 0°C for 2 hours under N2. Then thiazole- 4-carbaldehyde (5.00 g, 44.2 mmol, 1 eq) was added at 0°C and the reaction mixture was stirred for 1 hour under N2at 0°C. The mixture was warmed to 25°C and stirred for 12 hours under N2. The reaction mixture was quenched by aqueous NH4C1 (200 ml) at 0°C under N2. The mixture was extracted with ethyl acetate (200 mL x 2). The combined organic phases were washed with brine (200 mL x 2) and water (100 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by preparative HPLC (column: CD24-WePure Biotech XPT C18 150*25*7um; mobile phase: [H2O (0.1%TFA) - ACN]; gradient: 25% - 55% B over 12.0 min) to afford Reagent 1 (4.20 g, 27.1 mmol, 61.2% yield) as yellow oil.

[0555] To a mixture of Reagent 1 (874 mg, 4.56 mmol, 8.10 eq, HC1 salt) in DMSO (5 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (131 mg, 563 pmol, 1 eq) and pneumocandin bO (0.60 g, 563 pmol, 1 eq) at 25°C. The mixture was stirred at 25°C for 15 hours. Liquid Chromatography -Mass Spectrometry (LCMS) showed the reaction was completed and the desired m / z was detected. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (column: CD24-WePure Biotech XPT C18 150*25*7pm; mobile phase: [H2O (lOmM NH4HCO3) - ACN]; gradient: 40% - 70% B over 15.0 minutes) to afford Example 99 (40.0 mg, 32.1 pmol, 5.70% yield, 96.5% purity) as a white solid. MS (M+H): 1202.7 ;1H NMR: MeOD 400 MHz 5 = ppm 8.98 - 8.93 (m, 1H), 7.35 (d, J= 2.0 Hz, 1H), 7.16 (d, J= 8.4 Hz, 2H), 6.80 - 6.75 (m, 2H), 6.62 - 6.55 (m, 2H), 5.21 (d, J= 2.4 Hz, 1H), 5.11 (d, J= 4.0 Hz, 1H), 5.00 (d, J= 3.6 Hz, 1H), 4.62 - 4.54 (m, 3H), 4.52 - 4.47 (m, 1H), 4.41 - 4.32 (m, 3H), 4.32 - 4.28 (m, 3H), 4.16 - 4.09 (m, 1H), 4.05 - 3.94 (m, 2H), 3.81 (d, J= 11.2 Hz, 2H), 3.78 - 3.70 (m, 1H), 3.70 - 3.62 (m, 1H), 2.85 - 2.79 (m, 1H), 2.57 - 2.39 (m, 4H), 2.29 - 2.19 (m, 3H), 2.13 - 1.94 (m, 4H), 1.60 (t, J = 6.8 Hz, 2H), 1.50 - 1.34 (m, 4H), 1.33 - 1.22 (m, 13H), 1.21 - 1.17 (m, 3H), 1.16 - 1.01 (m, 3H), 0.97 - 0.83 (m, 11H).

[0556] Example 100:

[0557] To a mixture of 4-methylpyridazine (2.00 g, 21.3 mmol, 1.95 mL, 1 eq) in THF (20 mL) was added LDA (2 M, 10.6 mL, 1 eq) at -78°C under N2. The mixture was stirred at - 78°C for 2 hours under N2. Then 2-(3 -bromopropoxy) tetrahydropyran (4.98 g, 22.3 mmol, 1.05 eq) was added at -78°C under N2. The mixture was warmed to 25°C and stirred for 2 hours under N2. The reaction was quenched with IM HC1 to pH ~ 7 and extracted with dichloromethane (50 mL). The combined organic phase was washed with brine (50mL), dried over anhydrous Na2SO4, filtered and concentrated in vacuum. The residue was purified by preparative HPLC (column: CD27-Phenomenex luna Cl 8 250*70mm*10pm; mobile phase: [H2O (10mm NH4HCO3) - ACN]; gradient: 20% - 50% B over 30.0 minutes) to a mixture of this material (3.50 g, 14.8 mmol, 1 eq) in CH2C12(5 mL) was added TFA (2 mL) at 0°C under N2. The mixture was warmed to 25 °C and stirred for 15 hours under N2. LCMS showed the reaction was completed. The mixture was concentrated in vacuum to afford Reagent 1 (1.60 g, 6.01 mmol, 40.58% yield, TFA) as brown oil. MS (2M+H): 305.1 To a mixture of Reagent 1 (1.37 g, 5.16 mmol, 10 eq, TFA salt) in DMSO (5 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (120 mg, 516 pmol, 1 eq) and pneumocandin bO (0.55 g, 516 pmol, 1 eq) at 25°C under N2. The mixture was stirred at 25°C for 15 hours under N2. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (column: CD18-Welch Utimate Cl 8 150*40*7pm; mobile phase: [H2O (0.1%TFA) - ACN]; gradient: 25% - 55% B over 10.0 minutes) to afford Intermediate 1 (240 mg, 36.8% yield, 94.9% purity) as a white solid.

[0558] To a mixture of Intermediate 1 (80 mg, 66.7 pmol, 1 eq) in TFA (2 mL) was added Et3SiH (77.6 mg, 667 pmol, 107 pL, 10 eq) at 0°C. The mixture was stirred at 0°C for 1 hour. The reaction mixture was diluted with aqueous NaOAc solution (10 mL) at -5°C. The mixture was freeze-dried. The residue was purified by preparative HPLC (column: CD24- WePure Biotech XPT C18 150*25*7pm; mobile phase: [H2O (lOmM NH4HCO3) - ACN]; gradient: 40% - 70% B over 13.0 minutes) to afford Example 100 (50.0 mg, 41.1 pmol, 61.7% yield, 97.4% purity) as a white solid. MS (M+H): 1183.6 ; Hl NMR: MeOD 400 MHz 5 = ppm 9.04 (s, 1H), 8.66 (d, J= 5.2 Hz, 1H), 7.50 - 7.44 (m, 1H), 7.04 (d, J= 8.4 Hz, 2H), 6.76 - 6.69 (m, 2H), 5.19 (s, 1H), 5.12 (d, J= 2.8 Hz, 1H), 5.01 (d, J= 2.8 Hz, 1H), 4.71 - 4.63 (m, 2H), 4.62 - 4.57 (m, 5H), 4.55 (s, 2H), 4.51 - 4.43 (m, 2H), 4.41 - 4.33 (m, 2H), 4.30 (d, J= 3.6 Hz, 1H), 4.12 - 4.06 (m, 1H), 4.05 - 3.98 (m, 2H), 3.82 (d, J= 10.8 Hz, 2H), 3.68 - 3.62 (m, 1H), 3.56 - 3.50 (m, 1H), 2.84 (t, J= 7.6 Hz, 2H), 2.76 - 2.69 (m, 1H), 2.66 - 2.55 (m, 2H), 2.51 - 2.41 (m, 2H), 2.29 - 2.20 (m, 3H), 2.09 - 1.95 (m, 4H), 1.89 - 1.81 (m, 2H), 1.68 - 1.57 (m, 4H), 1.38 - 1.24 (m, 15H), 1.18 (d, J= 6.0 Hz, 3H), 1.14 - 1.05 (m, 2H), 0.96 - 0.84 (m, 12H).

[0559] Example 101:

[0560] To a mixture of 4-(lH-imidazol-l-yl)butan-l-ol (829 mg, 4.69 mmol, 10 eq, HC1 salt) in DMSO (1 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l-yl]methanesulfonic acid (109 mg, 469 pmol, 1 eq) and pneumocandin bO (0.50 g, 469 pmol, 1 eq) at 25°C. The mixture was stirred at 25°C for 15 hours. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (column: CD24-WePure Biotech XPT Cl 8 150*25*7um; mobile phase: [H2O (0.1%TFA) - ACN]; gradient: 30%-50% B over 14.0 min) to afford Example 101 (140 mg, 111 pmol, 23.6% yield, 94.0% purity) as a white solid. MS (M+H): 1187.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 9.06 - 8.97 (m, 1H), 8.69 - 8.55 (m, 1H), 8.29 (d, J= 9.2 Hz, 1H), 7.80 - 7.63 (m, 2H), 7.62 - 7.50 (m, 2H), 7.16 (d, J= 8.4 Hz, 2H), 6.82 - 6.73 (m, 2H), 5.22 - 5.08 (m, 3H), 5.02 - 4.98 (m, 2H), 4.62 - 4.55 (m, 3H), 4.55 - 4.48 (m, 1H), 4.41 - 4.37 (m, 1H), 4.34 - 4.26 (m, 6H), 4.09 - 4.02 (m, 1H), 4.01 - 3.94 (m, 2H), 3.87 - 3.79 (m, 2H), 3.65 - 3.57 (m, 2H), 2.81 - 2.74 (m, 1H), 2.55 - 2.41 (m, 2H), 2.24 (t, .7= 7.2 Hz, 3H), 2.13 - 1.94 (m, 7H), 1.65 - 1.57 (m, 4H), 1.53 - 1.39 (m, 4H), 1.36 - 1.27 (m, 12H), 1.23 - 1.18 (m, 3H), 1.14 - 1.05 (m, 2H), 0.95 - 0.86 (m, 10H).

[0561] Example 102:

[0562] To a solution of Example 126 (200 mg, 156 pmol, 1 eq) in dioxane (2 mL) were added Xphos-Pd-G2 (12.0 mg, 15.6 pmol, 0.1 eq), KOAc (30.0 mg, 313 pmol, 2 eq) and bis(pinacolato)diboron BPD (106 mg, 470 pmol, 3 eq) in one portion at 25°C under N2. The reaction mixture was degassed and purged with N25 times. The reaction mixture was heated to 100°C and stirred for 2 hours. After cooling to 20°C, the reaction mixture was quenched by H2O (10 mL) and extracted with EtOAc (10 mL x 2). The combined organic layers were washed with brine (10 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep-HPLC (column: Phenomenex luna Ci8100 x 40mm x 5 pm; mobile phase: [H20(0.04% HC1)-ACN]; gradient:35%-85% B over 8.0 minutes) to give Example 102 (32.3 mg, 23.6 pmol, 15.1% yield, 91.0% purity) as a white solid. MS: [M+H]+: 1241.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.64 - 8.62 (m, 1H), 8.25 - 8.15 (m, 2H), 8.03 - 8.00 (m, 1H), 7.81 - 7.78 (m, 1H), 7.55 - 7.53 (m, 1H), 7.44 - 7.41 (m, 1H), 7.30 - 7.15 (m, 6H), 6.85 - 6.76 (m, 2H), 5.15 - 5.11 (m, 2H), 5.00 - 4.97 (m, 2H), 4.62 - 4.44 (m, 5H), 4.40 - 4.28 (m, 5H), 4.10 - 3.94 (m, 3H), 3.87 - 3.78 (m, 2H), 3.63 - 3.51 (m, 2H), 2.83 - 2.77 (m, 1H), 2.64 - 2.61 (m, 1H), 2.54 - 2.43 (m, 2H), 2.30 - 2.19 (m, 3H), 2.11 - 1.93 (m, 4H), 1.69 - 1.55 (m, 7H), 1.52 - 1.37 (m, 4H), 1.36 - 1.24 (m, 13H), 1.19 (d, J = 6.0 Hz, 2H), 1.16 - 0.97 (m, 3H), 0.91 - 0.85 (m, 10H).

[0563] Example 103:

[0564] A mixture of pneumocandin bO (800 mg, 751 pmol, 1 eq), 4-(piperidin-4-yl)butan-l- ol hydrochloride (1.89 g, 9.76 mmol, 13 eq, HC1) and [(lS,4R)-7,7-dimethyl-2-oxo- norboman-l-yl]methanesulfonic acid (174 mg, 751 pmol, 1 eq) in DMSO (8 mL) was degassed and purged with N2for 3 times, and then the mixture was stirred at 25°C for 12 hours under N2atmosphere. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (CD18-Welch Utimate C18 150*40*7um; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 18%-48% B over 10.0 mi) to afford Example 103 (0.120 g, 96.9 pmol, 12.9% yield, 97.3% purity) as a white solid. MS (M+H): 1204.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.58 (br d, J= 8.4 Hz, 1H), 8.27 - 8.11 (m, 2H), 7.53 (br d, J= 8.4 Hz, 1H), 7.14 (d, J= 8.4 Hz, 2H), 6.75 (d, J= 8.4 Hz, 2H), 5.20 - 5.04 (m, 3H), 5.01 - 4.95 (m, 2H), 4.61 - 4.53 (m, 3H), 4.51 - 4.43 (m, 1H), 4.40 - 4.34 (m, 1H), 4.33 - 4.24 (m, 5H), 4.08 - 3.92 (m, 3H), 3.79 (br d, J = 10.0 Hz, 2H), 3.60 - 3.46 (m, 3H), 3.01 - 2.91 (m, 2H), 2.80 - 2.71 (m, 1H), 2.52 - 2.38 (m, 2H), 2.28 - 2.17 (m, 3H), 2.11 - 1.89 (m, 7H), 1.66 - 1.54 (m, 5H), 1.43 - 1.27 (m, 19H), 1.17 (br d, J = 6.0 Hz, 3H), 1.12 - 1.05 (m, 2H), 0.91 - 0.82 (m, 9H).

[0565] Example 104:

[0566] A solution of 4-(isopropylamino)butan-l-ol (2.00 g, 15.2 mmol, 1 eq) in HCl / di oxane (19 mL, 4 M) was stirred at 25°C for 1 hour. The reaction mixture was concentrated in vacuum to give Reagent 1 (3.00 g, crude, HC1 salt) as yellow gum, which was used in the next step directly without purification.

[0567] To a solution of Reagent 1 (3.00 g, 12.5 mmol, 19 eq, HC1 salt) in DMSO (15 mL) were added S-018 (700 mg, 657 pmol, 1 eq) and [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l- yl]methanesulfonic acid (153 mg, 657 pmol, 1 eq) at 25°C under N2. The reaction mixture was stirred at 25°C for 2 hour. The mixture was quenched by sodium bicarbonate aqueous solution (5%, 40 mL) at 25°C and extracted with EtOAc (30 mL x 3). The combined organic layers were washed with brine (30 mL x 2), dried over anhydrous Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (column: Phenomenex luna Ci8250 x 50mm x 15pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient:40%-60% B over 10.0 minutes) to give Example 104 (250 mg, 189 pmol, 28.8% yield, 98% purity, TFA salt) as a white solid. MS: [M+H]+1178.6. ;1H NMR: DMSO-t / 6400 MHz 5 = ppm 9.31 (s, 1 H) 8.15 - 8.32 (m, 4 H) 8.07 (d, J= 9.2 Hz, 1 H) 7.36 (d, J= 8.4 Hz, 1 H) 7.16 - 7.29 (m, 2 H) 7.01 (d, J= 8.4 Hz, 2 H) 6.74 (s, 1 H) 6.67 (d, J= 8.4 Hz, 2 H) 5.23 (d, J = 2.2 Hz, 1 H) 5.18 (s, 2 H) 4.92 - 5.01 (m, 2 H) 4.83 - 4.91 (m, 3 H) 4.81 (d, J= 5.4 Hz, 1 H) 4.77 (d, J= 5.8 Hz, 1 H) 4.41 (s, 1 H) 4.35 (d, J= 1.6 Hz, 1 H) 4.30 (m, 1 H) 4.10 - 4.25 (m, 5 H) 3.92 - 4.02 (m, 3 H) 3.87 (m, 1 H) 3.68 - 3.78 (m, 2 H) 3.55 - 3.61 (m, 1 H) 3.42 (d, J= 9.6 Hz, 1 H) 3.25 (m, 1 H) 2.87 (s, 2 H) 2.20 (m, 2 H) 2.01 - 2.11 (m, 3 H) 1.85 (m, 3 H) 1.69 - 1.77 (m, 1 H) 1.51 - 1.62 (m, 4 H) 1.39 - 1.49 (m, 4 H) 1.15 - 1.31 (m, 20 H) 0.99 - 1.09 (m, 5 H) 0.74 - 0.98 (m, 11 H).

[0568] Example 105:

[0569] To a mixture of Example 120 (0.10 g, 83.0 pmol, 1 eq) in TFA (1 mL) was added Et3SiH (96.5 mg, 830 pmol, 133 pL, 10 eq) at 0°C. The mixture was stirred at 0°C for 0.5 hour. After warming to room temperature, the reaction mixture was diluted with aq. NaOAc solution (10 mL) at -5°C. The mixture was freeze-dried. The residue was purified by preparative HPLC (column: CD24-WePure Biotech XPT C18 150*25 *7pm; mobile phase: [H2O (0.1%TFA) - ACN]; gradient: 25% - 55% B over 12.0 minutes) to afford Example 105 (46.0 mg, 38.1 pmol, 45.9% yield, 98.4% purity) as a white solid. MS (M+H): 1188.6 ; ’H NMR: MeOD 400 MHz 3 = ppm 8.60 - 8.49 (m, 1H), 8.32 - 8.22 (m, 1H), 8.21 - 8.15 (m, 1H), 7.79 - 7.71 (m, 1H), 7.57 (d, J= 8.4 Hz, 1H), 7.04 (d, J= 8.4 Hz, 2H), 6.72 (d, J= 8.4 Hz, 2H), 5.20 (d, J= 8.4 Hz, 1H), 5.15 - 5.11 (m, 1H), 5.04 - 5.00 (m, 2H), 4.70 - 4.62 (m, 2H), 4.61 - 4.48 (m, 5H), 4.47 - 4.28 (m, 5H), 4.07 - 3.95 (m, 3H), 3.87 - 3.80 (m, 2H), 3.63 - 3.49 (m, 3H), 3.43 - 3.38 (m, 2H), 3.11 - 2.95 (m, 2H), 2.72 - 2.40 (m, 6H), 2.30 - 2.23 (m, 3H), 2.12 - 1.95 (m, 6H), 1.92 (d, J = 11.6 Hz, 2H), 1.65 - 1.58 (m, 6H), 1.54 - 1.41 (m, 6H), 1.35 - 1.29 (m, 10H), 1.18 (d, J= 6.4 Hz, 3H), 1.15 - 1.06 (m, 2H), 0.96 - 0.86 (m, 11H).

[0570] Example 106:

[0571] To a mixture of Example 107 (0.10 g, 83.9 pmol, 1 eq) in TFA (1 mL) was added Et3SiH (97.5 mg, 839 pmol, 1345 pL, 10 eq) at 0°C. The mixture was stirred at 0°C for 1 hour. After warming to room temperature, the reaction mixture was diluted with aq. NaOAc solution (10 mL) at -5°C. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (column: CD18-Welch Utimate Cl 8 150*40*7pm; mobile phase: [H2O (0.1%TFA)-ACN]; gradient: 23% - 53% B over 10.0 minutes) to afford the desired product Example 106 (36.1 mg, 29.6 pmol, 35.3% yield, 96.6% purity) as a white solid. MS (M+H): 1176.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 8.57 (d, J= 8.4 Hz, 1H), 8.30 (d, J= 9.2 Hz, 1H), 8.16 (d, J= 8.0 Hz, 1H), 7.73 (d, J= 9.2 Hz, 1H), 7.56 (d, J= 8.4 Hz, 1H), 7.04 (d, J= 8.4 Hz, 2H), 6.72 (d, J= 8.4 Hz, 2H), 5.26 - 5.19 (m, 1H), 5.14 - 5.10 (m, 1H), 5.04 - 5.01 (m, 1H), 4.66 - 4.55 (m, 6H), 4.45 - 4.34 (m, 4H), 4.28 (d, J= 4.4 Hz, 1H), 4.14 - 3.92 (m, 5H), 3.83 (d, J= 11.2 Hz, 2H), 3.62 - 3.56 (m, 2H), 3.27 - 3.22 (m, 4H), 3.18 - 3.14 (m, 2H), 2.71 - 2.45 (m, 6H), 2.31 - 2.21 (m, 4H), 2.09 - 1.99 (m, 4H), 1.83 - 1.77 (m, 2H), 1.74 - 1.69 (m, 2H), 1.63 - 1.59 (m, 2H), 1.36 - 1.30 (m, 17H), 1.18 (d, J= 6.4 Hz, 3H), 1.10 (s, 1H), 0.92 - 0.85 (m, 11H).

[0572] Example 107:

[0573] To a mixture of 4-(diethylamino)butan-l-ol hydrochloride (1.11 g, 6.10 mmol, 10.0 eq, HC1 salt) in DMSO (3 mL) were added [(lS,4R)-7,7-dimethyl-2-oxo-norbornan-l- yl]methanesulfonic acid (142 mg, 610 pmol, 1 eq) and pneumocandin bO (650 mg, 610 pmol, 1 eq) at 25°C under N2. The mixture was stirred at 25°C for 15 hours under N2. The mixture was concentrated in vacuum. The residue was purified by preparative HPLC (column: CD 18-Welch Utimate C18 150*40*7pm; mobile phase: [H2O (0.1%TFA) - ACN]; gradient: 22% - 52% B over 10.0 min) to afford Example 107 (240 mg, 188 pmol, 30.8% yield, 93.5% purity) as a white solid. MS (M+H): 1192.3 ; ’H NMR: MeOD 400 MHz 3 = ppm 8.66 (d, J= 4.0 Hz, 1H), 8.31 (d, J= 9.2 Hz, 1H), 7.76 (d, J= 9.6 Hz, 1H), 7.54 (d, J = 8.4 Hz, 1H), 7.16 (d, J= 8.4 Hz, 2H), 6.77 (d, J= 8.4 Hz, 2H), 5.18 (d, J= 8.4 Hz, 1H), 5.14 - 5.09 (m, 1H), 5.02 - 4.99 (m, 1H), 4.61 - 4.56 (m, 3H), 4.54 - 4.48 (m, 1H), 4.42 - 4.29 (m, 6H), 4.29 - 4.26 (m, 1H), 4.12 - 4.05 (m, 1H), 3.98 (d, J= 9.6 Hz, 2H), 3.85 - 3.78 (m, 2H),

[0574] 3.60 (s, 2H), 3.26 - 3.21 (m, 4H), 3.17 (t, J= 7.6 Hz, 2H), 2.83 - 2.75 (m, 1H), 2.52 - 2.42 (m, 2H), 2.25 (t, J= 7.6 Hz, 3H), 2.10 - 1.97 (m, 4H), 1.85 - 1.77 (m, 2H), 1.72 - 1.66 (m, 2H),

[0575] 1.61 (s, 2H), 1.43 - 1.27 (m, 23H), 1.19 (d, J= 5.6 Hz, 3H), 1.14 - 1.09 (m, 1H), 0.95 - 0.86 (m, 11H).

[0576] Example 108:

[0577] To a mixture of pneumocandin bO (5.00 g, 4.69 mmol, 1 eq) and benzyl N-(4- hydroxybutyl)carbamate (15.0 g, 67.2 mmol, 14.3 eq) in DMSO (30 mL) was added [(lS,4R)-7,7-dimethyl-2-oxo-norboman-l-yl]methanesulfonic acid (1.09 g, 4.69 mmol, 1 eq) in one portion at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched with saturated Na2CO3(70 mL) and concentrated under reduce pressure to give a residue. The residue product was purified by reversed-phase HPLC (0.1% TFA condition) to give Intermediate 1 (4.00 g, 2.33 mmol, 49.6% yield, 74.0% purity) as a white solid.

[0578] To a solution Intermediate 1 (3.50 g, 2.75 mmol, 1 eq) in MeOH (40 mL) was added Pd / C (900 mg, 10% purity) at 25°C under Ar atmosphere. The suspension was degassed and purged with H2for 3 times. The reaction mixture was stirred under H2atmosphere (15 Psi) at 25°C for 1 hour. The reaction mixture was filtered and concentrated under reduce pressure to give Example 108 (2.8 g, crude) as a white solid. MS (M+H): 1136.5 ; ’H NMR: DMSO-t / 6400 MHz 5 = ppm 9.30 (s, 1H), 8.21 (d, J= 8.0 Hz, 2H), 8.06 (d, J= 92 Hz, 1H), 7.63 (br s, 3H), 7.36 (d, J= 92 Hz, 1H), 7.26 - 7.17 (m, 2H), 7.01 (d, J= 8.4 Hz, 2H), 6.74 (br s, 1H), 6.67 (d, .7= 8.4 Hz, 2H), 5.22 (d, J = 4.8 Hz, 1H), 5.18 - 5.16 m, 2H), 4.96 - 4.84 (m, 5H), 4.81 (d, J= 6.0 Hz, 1H), 4.79 - 4.75 (m, 1H), 4.42 (br s, 1H), 4.38 - 4.27 (m, 2H), 4.26 - 4.20 (m, 2H), 4.19 - 4.15 (m, 2H), 4.14 - 4.10 (m, 1H), 4.03 - 3.92 (m, 3H), 3.87 (d, J= 6.4 Hz, 1H), 3.78 - 3.68 (m, 2H), 3.62 - 3.54 (m, 1H), 3.45 - 3.38 (m, 1H), 2.77 (br s, 2H), 2.25 - 2.14 (m, 2H), 2.12 - 2.02 (m, 3H), 1.90 - 1.80 (m, 3H), 1.52 (br s, 3H), 1.47 - 1.35 (m, 4H), 1.34 - 1.16 (m, 15H), 1.11 - 1.01 (m, 5H), 0.93 - 0.80 (m, 11H). Example 109:

[0579] To a solution of Example 170 (26.0 mg, 22.3 pmol, 1 eq, TFA) in TFA (0.50 mL) was added triethylsilane (TESH) (25.0 mg, 223 pmol, 10 eq) in one portion at 25°C under N2. The reaction mixture was stirred at 25°C for 1 hour. The reaction mixture was quenched by H2O (1 mL) at 25°C. The mixture was dried by lyophilization to give Example 109 (17.1 mg, 13.2 pmol, 59.7% yield, 98.5% purity, TFA) as a white solid. MS: [M+H+] 1147.6 ;1H NMR: MeOD 400 MHz 5 = ppm 7.66 - 7.62 (m, 1H), 7.54 - 7.49 (m, 1H), 7.01 (d, J= 8.4 Hz, 2H), 6.82 (d, J= 8.8 Hz, 2H), 5.09 - 5.01 (m, 4H), 4.66 - 4.51 (m, 6H), 4.43 - 4.35 (m, 4H), 4.04 - 3.81 (m, 6H), 3.31 - 3.20 (m, 4H), 2.92 (s, 6H), 2.67 - 2.32 (m, 6H), 2.31 - 1.97 (m, 10H), 1.61 - 1.57 (m, 2H), 1.51 - 1.36 (m, 4H), 1.34 - 1.22 (m, 15H), 1.16 - 1.13 (m, 4H), 1.10 - 0.92 (m, 4H), 0.90 - 0.85 (m, 10H).

[0580] Example 110:

[0581] To a mixture of Example 169 (250 mg, 231 pmol, 1 eq) and 2-(4-(4, 4,5,5- tetramethyl-l,3,2-dioxaborolan-2-yl)phenyl)acetaldehyde (85.0 mg, 347 pmol, 1.5 eq) in MeOH (3 mL) was added AcOH (14.0 mg, 231 pmol, 1 eq) at 20°C under N2. The mixture was stirred at 20°C for 1 hour. Then triacetoxysodiumborohydride (NaBH(OAc)3) (196 mg, 927 pmol, 4 eq) was added at 20°C. The mixture was stirred at 20 °C for 12 hours. The reaction mixture was quenched by H2O (5 mL) and extracted with EtOAc (5 mL x 3). The combined organic layers were washed with brine (5 mL x 3), dried over Na2SO4, filtered and concentrated under reduced pressure to give a residue. The residue was purified by prep- HPLC (column: Phenomenex Luna Ci8 75 x 30mm x 3pm; mobile phase: [H2O (0.1% TFA)- ACN]; gradient: 25%-55% B over 8.0 minutes) to give Example 110 (23.6 mg, 17.6 pmol, 7.59% yield, TFA) as a white solid. MS (M+H): 1226.6 ; ’H NMR: MeOD 400 MHz 5 = ppm 7.75 (d, J= 6.8 Hz, 2H), 7.26 (d, J= 7.2 Hz, 2H), 7.15 (d, J= 8.4 Hz, 2H), 6.76 (d, J = 8.4 Hz, 2H), 5.05 (d, J= 3.6 Hz, 1H), 4.63 - 4.59 (m, 4H), 4.52 - 4.47 (m, 2H), 4.39 - 4.30 (m, 3H), 4.19 - 4.09 (m, 2H), 4.02 - 3.75 (m, 5H), 3.54 - 3.47 (m, 1H), 3.42 (d, J= 4.4 Hz, 1H), 3.28 (d, J= 2.0 Hz, 1H), 3.07 - 2.96 (m, 2H), 2.65 - 2.38 (m, 3H), 2.26 - 1.90 (m, 6H), 1.83 - 1.71 (m, 1H), 1.67 - 1.56 (m, 2H), 1.55 - 1.00 (m, 22H), 0.97 - 0.81 (m, 10H).

[0582] Example 111:

[0583] To a mixture of Echinocandin B, l-[(4R,5R)-4,5-dihydroxy-L-ornithine]- (100 mg, 120 pmol, 1 eq, HC1) and tetradecanal (25.5 mg, 120 pmol, 1 eq) in MeOH (1 mL) was added a drop of AcOH at 25°C and stirred for 1 hour. Then NaBH(OAc)3(127 mg, 599 pmol, 5 eq) was added at 25°C. The reaction mixture was stirred at 25°C for 16 hours. The reaction mixture was quenched with H2O 5 mL, filtered and concentrated under reduce pressure to give a residue. The residue was purified by prep-HPLC (TFA condition: column: Welch Ultimate Ci8 120 x 30mm x 5pm; mobile phase: [H2O (0.1% TFA)-ACN]; gradient: 35%- 75% B over 20.0 minutes) to give Example 111 (31.1 mg, 28.0 pmol, 23.4% yield, TFA) as a white solid. MS (M+H): 994.5 ; ’H NMR: DMSO-t / 6400 MHz 5 = ppm 9.33 (s, 1H), 8.99 - 8.84 (m, 1H), 8.58 (br s, 1H), 8.17 (d, J= 6.0 Hz, 1H), 8.09 (d, J= 8.8 Hz, 1H), 7.50 (d, J = 9.2 Hz, 1H), 7.03 (d, J= 8.4 Hz, 2H), 6.69 (d, J= 8.4 Hz, 2H), 5.92 (d, J= 2.8 Hz, 1H), 5.38 - 5.22 (m, 3H), 5.16 (br s, 1H), 5.09 (t, J= 4.4 Hz, 2H), 4.87 (br s, 1H), 4.69 - 4.61 (m, 2H), 4.47 - 4.40 (m, 2H), 4.33 (s, 1H), 4.26 - 4.17 (m, 3H), 4.11 - 4.01 (m, 3H), 3.81 - 3.72 (m, 4H), 3.18 (br t, J= 10.0 Hz, 1H), 2.82 - 2.66 (m, 2H), 2.33 - 2.19 (m, 2H), 2.05 - 1.97 (m, 1H), 1.95 - 1.87 (m, 1H), 1.79 - 1.70 (m, 1H), 1.61 - 1.50 (m, 2H), 1.24 (s, 25H), 1.03 (d, J=

[0584] 6.4 Hz, 3H), 0.96 (d, J= 6.4 Hz, 3H), 0.86 (t, J= 6.4 Hz, 3H).

[0585] Example 112:

[0586] To a mixture of Example 157 (140 m...

Claims

WHAT IS CLAIMED IS:

1. A composition, comprising at least one antifungal compound having the structure set forth in Formula I and an agriculturally suitable adjuvant:Formula I wherein:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, CH2Q, N3, NO2, Cl, F, Br, and I;X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and OC(O)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; andeach of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

2. The composition according to claim 1, further comprising one or more additional fungicidal compounds.

3. A composition, comprising at least one antifungal compound having the structure set forth in Formula II and an agriculturally suitable adjuvant:wherein:U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;T is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and C(O)OR; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof.

4. The composition according to claim 3, wherein T is selected from the group consisting of C(O)Me, C(O)OMe, CH2CH2NH2, and CH2CO2Me.

5. The composition according to claim 3 or 4, further comprising one or more additional fungicidal compounds.

6. A composition, comprising at least one antifungal compound having the structure set forth in Formula III and an agriculturally suitable adjuvant,Formula ill wherein:U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof.

7. The composition according to claim 6, wherein X is selected from a group consisting of iodine, SO3H, NHC(O)CH2CH2COOH, and C=CH.

8. The composition according to claim 6 or 7, further comprising one or more additional fungicidal compounds.

9. A composition comprising at least one antifungal compound having the structure set forth in Formula IV and an agriculturally suitable adjuvant:Formula IV wherein:U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, and (N)OR; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and, each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof.

10. The composition according to claim 9, further comprising one or more additional fungicidal compounds.

11. A composition, comprising at least one antifungal compound having the structure set forth in Formula V and an agriculturally suitable adjuvant:Formula V wherein:U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;W is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(O)M, C(S)M, C(N)R”M, S(O)2M, P(O)MM, CH2Q and CV each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, aryl, and heteroaryl; and salts thereof.

12. The composition according to claim 11, wherein W is selected from a group consisting of C(O)NH2, C(O)OCH2CH3, CH2NH2, and cyano.

13. The composition according to claim 11 or 12, further comprising one or more additional fungicidal compounds.

14. At least one antifungal compound having the structure set forth in Formula VI and an agriculturally suitable adjuvant:Formula VI wherein:U is selected from the group consisting of n-alkyl, branched alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

15. The composition according to claim 14, further comprising one or more additional fungicidal compounds.

16. The composition according to any of claims 1-15, wherein a hemi-aminal functional group of the at least one antifungal compound is replaced by a hemiaminal ether, a thioaminal or an aminal, wherein the composition gains greater aqueous stability and has greater whole plant activity relative to pneumocandin.

17. A method for controlling or treating a disease in a plant, comprising: applying to the plant at least one antifungal compound, wherein the at least one antifungal compound is selected from a lipophilic cyclic hexapeptidal candin / fungin derivative (echinocandin) having the structure set forth in one of Formulas I- VI.

18. A composition comprising at least one antifungal compound having the structure set forth in Formula VII and an agriculturally suitable adjuvant:Formula VII wherein:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’,NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, heteroaryl; and salts thereof.

19. The composition of claim 18, further comprising one or more additional fungicidal compounds.

20. A composition comprising at least one antifungal compound having the structure set forth in Formula VIII and an agriculturally suitable adjuvant:Formula VIII wherein:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’,NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

21. The composition of claim 20, further comprising one or more additional fungicidal compounds.

22. A composition comprising at least one antifungal compound having the structure set forth in Formula IX and an agriculturally suitable adjuvant:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;A is N or O; n is 0-3;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is independently selected from the group consisting of OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

23. The composition according to claim 22, further comprising one or more additional fungicidal compounds.

24. A composition comprising at least one antifungal compound having the structure set forth in Formula X and an agriculturally suitable adjuvant:wherein:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl;A is N or O; n is 0-3;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM,0C(0)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

25. The composition of claim 24, further comprising one or more additional fungicidal compounds.

26. A composition comprising at least one antifungal compound having the structure set forth in Formula XI and an agriculturally suitable adjuvant:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

27. The composition according to claim 26, further comprising one or more additional fungicidal compounds.

28. A composition comprising at least one antifungal compound having the structure set forth in Formula XII and an agriculturally suitable adjuvant:U is selected from the group consisting of alkyl, aryl, heteroalkyl, and heteroaryl;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;W is carbonyl or CH2;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(O)M, C(S)M, C(N)R”M, S(O)2M, and P(O)MM,OC(O)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’, NS(O2)R, or taken together with an adjacent hydroxyl to form a 6-8-membered heterocycle; and each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

29. The composition of claim 28, further comprising one or more additional fungicidal compounds.

30. The composition of any one of claims 18-29, wherein a hemi-aminal functional group of the antifungal compound is replaced by an amide, methylamide, a hemiaminal ether, a thioaminal, aminoaminal methylamino, or an aminal, wherein the composition gains greater aqueous stability and has greater whole plant activity relative to pneumocandin.

31. A method for controlling or treating a disease in a plant, comprising: applying to the plant at least one antifungal compound, wherein the at least one antifungal compound is selected from a lipophilic cyclic candin / fungin derivative (echinocandin) having the structure set forth in one of Formulas VII - XII.

32. The method of claim 31, where the lipophilic cyclin candin / fungin derivative is hexapeptidal.

33. A compound for controlling or treating a disease in a plant, wherein said compound comprises the structure set forth in one of Formulas VII - XII.

34. A composition comprising at least one antifungal compound having the structure set forth in Formula XIII and an agriculturally suitable adjuvant:Formula XIII wherein:U is selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl,C(O)alkyl, C(O)aryl, C(O)heteroalkyl, and C(O)heteroaryl or a group consisting of:K is either H or -OH;V is selected from the group consisting of H, methyl, and hydroxyl; n is 0-3;L is -OH, -B(OH)2, -B(OR)2or selected from a group consisting of:is independently alkyl and joined as ring or alkyl-substituted ring and n is 0-3;A is O or NH;W is alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, C(O)M, C(S)M,substituted ring and n is 0-3;X is selected from the group consisting of H, alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, and P(0)MM;Y is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, OR, SR, NRR’, (O), F, Cl, Br, I, C(0)M, C(S)M, C(N)R”M, S(O)2M, P(0)MM, and OC(O)R;Z is selected from the group consisting of H, alkyl, heteroalkyl, aryl, heteroaryl, OH, CN OR, SR, NRR’, (O), F, Cl, Br, I, and CH2Q; each M is independently selected from the group consisting of alkyl, aryl, heteroalkyl, heteroaryl, cycloalkyl, heterocycloalkyl, OR’, SR’, NR’R”, and N(+)RR’R”;Q is OR, SR, NRR’, N(+)RR’R”, N3, NO2, Cl, F, Br, I, NR(CO)R’ or NS(O2)R, or taken together with K to form a 6-8-membered heterocycle; each of R, R’, and R” is independently selected from the group consisting of H, alkyl, alkenyl, alkynyl, heteroalkyl, (CH2)n-heteroalkyl, aryl, and heteroaryl; and salts thereof.

35. A method for controlling or treating a disease in a plant, comprising: applying to the plant at least one antifungal compound, wherein the at least one antifungal compound is selected from a lipophilic cyclic candin / fungin derivative (echinocandin) having the structure set forth in one of Formulas XIII.

36. The composition of claim 34, further comprising one or more additional fungicidal compounds.

37. The method of claim 34, where the lipophilic cyclin candin / fungin derivative is hexapeptidal.

38. A compound for controlling or treating a disease in a plant, wherein said compound comprises the structure set forth in one of Formulas XIII.

39. The composition of any one of claims 34-38, wherein a hemi-aminal functional group of the antifungal compound is replaced by an amide, methylamide, a hemiaminal ether, a thioaminal, aminoaminal methylamino, or an aminal, wherein the composition gains greater aqueous stability and has greater whole plant activity relative to pneumocandin.

40. A method for controlling or treating a disease in a plant, comprising: applying to the plant an antifungal compound selected from the group consisting of the following compounds:

Images