Compositions and methods to control bacterial pathogens in monocot plants

Abstract

This application relates to the use of ascaroside compositions to mitigate the effects of bacterial pathogens in rice.

Description

[0001] COMPOSITIONS AND METHODS TO CONTROL BACTERIAL PATHOGENS IN MONOCOT PLANTS

[0002] CROSS-REFERENCE TO RELATED APPLICATIONS

[0003]

[0001] This application claims the benefit of priority to U.S. Provisional Appl. No. 63 / 763, 179, filed February 25, 2025, the entirety of which is hereby incorporated by reference.

[0004] FIELD OF THE INVENTION

[0005]

[0002] This application generally relates to agrichemical compounds, compositions, and methods of protecting crops from bacterial pathogens.

[0006] BACKGROUND OF THE INVENTION

[0007]

[0003] Ascaroside natural products are secondary metabolites produced by nematodes. A large number of structurally diverse ascarosides have been identified in nature and the molecules are believed to function as an evolutionanly conserved chemical language used by nematodes to control many aspects of their development. Ascarosides are also perceived by other organisms and have been demonstrated to have a range of effects on numerous organisms including bacteria, fungi, plants, and mammals including humans. Ascarosides hold potential as human medicines, agrichemicals and products for other diverse and valuable applications.

[0008]

[0004] Ascaroside treatments have been demonstrated to show efficacy in increasing plant resistance to certain pathogens and / or in inducing and priming plant defense responses (which can inhibit pathogen growth and / or infestation) when applied to the plant. By activating and / or priming plants’ innate defenses, ascarosides can thereby prevent proliferation of pathogens and / or protect crops from the damaging effects caused by diverse pathogens.

[0009]

[0005] Bacterial pathogens in monocot crop plants are a serious problem that can reduce agricultural yields and gram quality'. The control of bacterial pathogens in monocot. crop plants is more difficult since there are few bactericidal agents approved for use in field and those that are available have shortcomings. For example, copper is a common treatment for bacterial pathogens in some monocot crops, but it must be used frequently and at high rates. Additionally, copper is toxic to soil organisms such as earthworms and beneficial microbes and can accumulate in the soil after repeated use to levels that are toxic to the crop plants. Another common practice is to apply antibiotic compounds, such as streptomycin and tetracycline, that are also used as human medicines. Use of human antibiotics is problematic since it increases

[0010] 331652340 ASCB-018 / 01WO (360511-2180)the risk of widespread antibiotic resistance and risks accelerating the emergence of multidrug resistant bacterial infections in humans. The present invention addresses these issues and related problems.

[0011] SUMMARY OF THE INVENTION

[0012]

[0006] In one aspect, the present disclosure provides the recognition that ascarosides are effective in treating monocot plants infected with or exposed to bacterial pathogens, and / or preventing or reducing damage to monocot plants by bacterial pathogens. In another aspect, the present disclosure provides the recognition that the application of ascarosides can increase yields of monocot plants exposed to bacterial pathogens. While ascarosides’ ability to prime and / or activate plant defenses and thereby provide a useful means to protect certain plants from certain bacterial pathogens has been disclosed in laboratory settings, to date the specific protocols for using ascarosides to control bacterial pathogens in certain field settings where such protection is needed remain untested. In some embodiments, the present disclosure encompasses the recognition that application of ascarosides to monocot plants for control of bacterial pathogens is effective, even at low application rates. Additionally or alternatively, without wishing to be bound to a particular theory, it has been found that the treatments are more effective when performed at least twice in succession within particular treatment intervals — this is surprising given the plant-defense-priming mode of action of the molecules since it has been demonstrated that a single treatment is sufficient to prime plant defenses, with repeated treatments lacking significant increases in efficacy.

[0013]

[0007] In some embodiments, the present disclosure provides methods for treating monocot plants exposed to or infected with bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In certain embodiments, the present disclosure provides methods for preventing or reducing damage to monocot plants from bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In some embodiments, the present disclosure provides methods for increasing yields of monocot plants exposed to bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In some embodiments, the present disclosure provides methods of controlling pathogens of the genus Xanthomonas in rice, the method comprising applying one or more ascarosides to the foliage of the plant.

[0014]

[0008] In some embodiments, provided methods comprise applying one or more ascarosides to the plant at less than 250 mg per hectare (mg / ha). In some embodiments, provided methods

[0015] 331652340 ASCB-018 / 01WO (360511-2180)comprising applying the one or more ascarosides via foliar spray. In some embodiments, the concentration of the one or more ascarosides within the foliar spray is 0.5 mg / L or less.

[0016]

[0009] In some embodiments, the application of the one or more ascarides is performed at least two times during the growing season. In certain embodiments, the interval between two applications (e.g., the first and second application) is at least 7 days. In certain embodiments, the ascaroside is a glycoside of a Cs-4o co- 1 hydroxy fatty acid or an ester, amide, or salt thereof, or is a glycoside of a Cs-40 co-hydroxy fatty acid or an ester, amide, or salt thereof. In certain embodiments, the monocot plant comprises rice. In certain embodiments, the bacterial pathogen comprises a member of the genus Xanthomonas . In certain embodiments, a method is characterized in that the ascaroside is applied at a rate less than 100 mg / ha or 50 mg / ha. In certain embodiments, a method is characterized in that the damage from bacterial pathogens is reduced by at least 50%, at least 60%, at least 70%, or at least 80% as compared to a corresponding plant or population of plants not treated with the one or more ascarosides. In some embodiments, a method is characterized in that the yield is increased by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, or at least 40% as compared to a corresponding plant or population of plants not treated with the one or more ascarosides or ascaroside composition.

[0017]

[0010] In certain embodiments, the ascaroside is applied in combination with a fungicide. In certain embodiments, the ascaroside is applied in combination with a fungicide, wherein the fungicide is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, or a lower amount / hectare).

[0018] [OH] In certain embodiments, the ascaroside is applied in combination with a bactericide. In certain embodiments, the ascaroside is applied in combination with a bactericide, wherein the bactericide is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application).

[0019]

[0012] In certain embodiments, the ascaroside is applied in combination with a copper composition, wherein the copper composition is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application).

[0020]

[0013] In some embodiments, a lower than typical rate and / or amount is the rate or amount approved or recommended by a regulatory authority for a given fungicide or bactericide.

[0021]

[0014] These and other features, aspects, and advantages of the disclosure will be apparent from a reading of the following detailed description together with the accompanying drawings,

[0022] 331652340 ASCB-018 / 01WO (360511-2180)which are briefly described below. The invention includes any combination of two, three, four, or more of the above-noted embodiments as well as combinations of any two, three, four, or more features or elements set forth in this disclosure, regardless of whether such features or elements are expressly combined in a specific embodiment description herein. This disclosure is intended to be read holistically such that any separable features or elements of the disclosed invention, in any of its various aspects and embodiments, should be viewed as intended to be combinable unless the context clearly dictates otherwise. Other aspects and advantages of the present disclosure will become apparent from the following.

[0023] BRIEF DESCRIPTION OF THE DRAWINGS

[0024]

[0015] The present teachings described herein will be more fully understood from the following description of various illustrative embodiments, when read together with the accompanying drawings. It should be understood that each drawing described below is for illustration purposes only and is not intended to limit the scope of the present teachings in any way. The foregoing and other objects, aspects, features, and advantages of the disclosure will become more apparent and may be better understood by referring to the following description taken in conjunction with the accompanying drawings, in which:

[0025]

[0016] Figure 1 is a chart showing the reduction in bacterial leaf blight severity in rice plants treated with an ascaroside at different application rates.

[0026]

[0017] Figure 2 is a chart showing the reduction in bacterial leaf blight severity in rice plants treated with compositions containing ascaroside in combination with commercial fungicides.

[0027]

[0018] Figure 3 is a chart showing the yield obtained from rice treated with an ascaroside relative to the yield obtained from rice not treated with the ascaroside.

[0028] DEFINITIONS

[0029]

[0019] In order for the present disclosure to be more readily understood, certain terms are first defined below. Additional definitions for the following terms and other terms are set forth throughout the specification.

[0030]

[0020] In this application, unless otherwise clear from context, the term “a” may be understood to mean “at least one.” As used in this application, the term “or” may be understood to mean “and / or.” In this application, the terms “comprising” and “including” may be understood to encompass itemized components or steps whether presented by themselves or together with one or more additional components or steps. As used in this application, the term “comprise”

[0031] 331652340 ASCB-018 / 01WO (360511-2180)and variations of the term, such as “comprising” and “comprises,” are not intended to exclude other additives, components, integers or steps.

[0032]

[0021] As used herein, the terms “about” and “approximately” are used as equivalents. Unless otherwise stated, the terms “about” and “approximately” may be understood to permit standard variation as would be understood by those of ordinary skill in the art. Where ranges are provided herein, the endpoints are included. Any numerals used in this application with or without about / approximately are meant to cover any normal fluctuations appreciated by one of ordinary skill in the relevant art. In some embodiments, the term “approximately” or “about” refers to a range of values that fall within 25 %, 20 %, 19 %, 18 %, 17 %, 16 %, 15 %, 14 %, 13 %, 12 %, 11 %, 10 %, 9 %, 8 %, 7 %, 6 %, 5 %, 4 %, 3 %, 2 %, 1 %, or less in either direction (greater than or less than) of the stated reference value unless otherwise stated or otherwise evident from the context (except where such number would exceed 100 % of a possible value).

[0033]

[0022] Definitions of specific functional groups and chemical terms are described in more detail below. For purposes of this invention, the chemical elements are identified in accordance with the Periodic Table of the Elements, CAS version, Handbook of Chemistry and Physics, 75thEd., inside cover, and specific functional groups are generally defined as described therein. Additionally, general principles of organic chemistry, as well as specific functional moieties and reactivity, are described in Organic Chemistry, Thomas Sorrell, University Science Books, Sausalito, 1999; Smith and March March ’s Advanced Organic Chemistry, 5thEdition, John Wiley & Sons, Inc., New York, 2001; Larock, Comprehensive Organic Transformations, VCH Publishers, Inc., New York, 1989; Carruthers, Some Modern Methods of Organic Synthesis, 3rdEdition, Cambridge University Press, Cambridge, 1987; the entire contents of each of which are incorporated herein by reference.

[0034]

[0023] Certain compounds provided herein can comprise one or more asymmetric centers, and thus can exist in various stereoisomeric forms, e.g., enantiomers and / or diastereomers. Thus, inventive compounds and compositions thereof may be in the form of an individual enantiomer, diastereomer or geometric isomer, or may be in the form of a mixture of stereoisomers. In certain embodiments, compounds described herein are enantiopure compounds. In certain other embodiments, mixtures of enantiomers or diastereomers are provided.

[0035]

[0024] Furthermore, certain compounds as described herein may have one or more double bonds that can exist as either a Z or E isomer, unless otherwise indicated. The compounds can

[0036] 331652340 ASCB-018 / 01WO (360511-2180)be provided as individual isomers substantially free of other isomers and alternatively, as mixtures of various isomers, e.g., racemic mixtures of enantiomers.

[0037]

[0025] As used herein, the term “isomers” includes any and all geometric isomers and stereoisomers. For example, “isomers” include cis- and (ram-isomers. E- and Z- isomers, R-and S-enantiomers, diastereomers, (D)-isomers, (L)-isomers, racemic mixtures thereof, and other mixtures thereof, as falling within the scope of the disclosure. For instance, a compound may, in some embodiments, be provided substantially free of one or more corresponding stereoisomers, and may also be referred to as “stereochemically enriched.”

[0038]

[0026] Where a particular enantiomer is preferred, it may, in some embodiments be provided substantially free of the opposite enantiomer, and may also be referred to as “optically enriched.” “Optically enriched,” as used herein, means that the compound is made up of a significantly greater proportion of one enantiomer. In certain embodiments the compound is made up of at least about 90% by weight of an enantiomer. In some embodiments the compound is made up of at least about 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9% by weight of an enantiomer. In some embodiments the enantiomeric excess of provided compounds is at least about 90%, 95%, 97%, 98%, 99%, 99.5%, 99.7%, 99.8%, or 99.9%. In some embodiments, enantiomers may be isolated from racemic mixtures by any method known to those skilled in the art, including chiral high pressure liquid chromatography (HPLC) and the formation and crystallization of chiral salts or prepared by asymmetric syntheses. See, for example, Jacques, et al., Enantiomers, Racemates and Resolutions (Wiley Interscience, New York, 1981); Wilen, S.H., et al., Tetrahedron 33:2725 (1977); Eliel, E.L. Stereochemistry of Carbon Compounds (McGraw-Hill, NY, 1962); Wilen, S.H. Tables of Resolving Agents and Optical Resolutions p. 268 (E.L. Eliel, Ed., Univ, of Notre Dame Press, Notre Dame, IN 1972).

[0039]

[0027] The terms “halo” and “halogen” as used herein refer to an atom selected from fluorine (fluoro, -F), chlorine (chloro, -Cl), bromine (bromo, -Br), and iodine (iodo, -I).

[0040]

[0028] The term “aliphatic” or “aliphatic group”, as used herein, denotes a hydrocarbon moiety that may be straight-chain (i.e., unbranched), branched, or cyclic (including fused, bridging, and spiro-fused polycyclic) and may be completely saturated or may contain one or more units of unsaturation, but which is not aromatic. Unless otherwise specified, aliphatic groups contain 1-30 carbon atoms. In certain embodiments, aliphatic groups contain 1-12 carbon atoms. In certain embodiments, aliphatic groups contain 1-8 carbon atoms. In certain embodiments, aliphatic groups contain 1-6 carbon atoms. In some embodiments, aliphatic groups contain 1-5 carbon atoms, in some embodiments, aliphatic groups contain 1-4 carbon atoms, in yet other

[0041] 331652340 ASCB-018 / 01WO (360511-2180)embodiments aliphatic groups contain 1-3 carbon atoms, and in yet other embodiments aliphatic groups contain 1-2 carbon atoms. Suitable aliphatic groups include, but are not limited to, linear or branched, alkyl, alkenyl, and alkynyl groups, and hybrids thereof such as (cycloalkyl)alkyl, (cycloalkenyl)alkyl or (cycloalkyl)alkenyl.

[0042]

[0029] The term “heteroaliphatic” or “heteroaliphatic group”, as used herein, denotes an aliphatic group where one or more carbon or hydrogen atoms are replaced by a heteroatom (e.g. oxygen, nitrogen, sulfur, phosphorous, boron, etc.). In some embodiments, a heteroaliphatic group is a heterocyclyl group.

[0043]

[0030] The term "unsaturated", as used herein, means that a moiety has one or more double or triple bonds.

[0044]

[0031] The term “alkyl,” as used herein, refers to saturated, straight- or branched-chain hydrocarbon radicals derived from an aliphatic moiety containing between one and six carbon atoms by removal of a single hydrogen atom. Unless otherwise specified, alkyl groups contain 1-12 carbon atoms. In certain embodiments, alkyl groups contain 1-8 carbon atoms. In certain embodiments, alkyl groups contain 1-6 carbon atoms. In some embodiments, alkyl groups contain 1-5 carbon atoms, in some embodiments, alkyl groups contain 1-4 carbon atoms, in yet other embodiments alkyl groups contain 1-3 carbon atoms, and in yet other embodiments alkyl groups contain 1-2 carbon atoms. Examples of alkyl radicals include, but are not limited to, methyl, ethyl, n-propyl, isopropyl, n-butyl, iso-butyl, sec-butyl, sec-pentyl, iso-pentyl, tert-butyl, n-pentyl, neopentyl, n-hexyl, sec-hexyl, n-heptyl, n-octyl, n-decyl, n-undecyl, dodecyl, and the like.

[0045]

[0032] The term “alkenyl,” as used herein, denotes a monovalent group derived from a straight- or branched-chain aliphatic moiety having at least one carbon-carbon double bond by the removal of a single hydrogen atom. Unless otherwise specified, alkenyl groups contain 2-12 carbon atoms. In certain embodiments, alkenyl groups contain 2-8 carbon atoms. In certain embodiments, alkenyl groups contain 2-6 carbon atoms. In some embodiments, alkenyl groups contain 2-5 carbon atoms, in some embodiments, alkenyl groups contain 2-4 carbon atoms, in yet other embodiments alkenyl groups contain 2-3 carbon atoms, and in yet other embodiments alkenyl groups contain 2 carbon atoms. Alkenyl groups include, for example, ethenyl, propenyl, butenyl, l-methyl-2-buten-l-yl, and the like.

[0046]

[0033] The term “aryl” used alone or as part of a larger moiety as in “aralkyl”, “aralkoxy”, or “aryloxyalkyl”, refers to monocyclic and polycyclic ring systems having a total of five to 20 ring members, wherein at least one ring in the system is aromatic and wherein each ring in the

[0047] 331652340 ASCB-018 / 01WO (360511-2180)system contains three to twelve ring members. The term “aryl” may be used interchangeably with the term “aryl ring”. In certain embodiments, “aryl” refers to an aromatic ring system which includes, but is not limited to, phenyl, biphenyl, naphthyl, anthracyl and the like, which may bear one or more substituents. Also included within the scope of the term aryl”, as it is used herein, is a group in which an aromatic ring is fused to one or more additional rings, such as benzofuranyl, indanyl, phthalimidyl, naphthimidyl, phenantriidinyl, or tetrahydronaphthyl, and the like.

[0048]

[0034] The terms “heteroaryl” and “heteroar-,” used alone or as part of a larger moiety, e.g., “heteroaralkyl,” or “heteroaralkoxy,” refer to groups having 5 to 10 ring atoms, preferably 5, 6, or 9 ring atoms; having 6, 10, or 14 n electrons shared in a cyclic array; and having, in addition to carbon atoms, from one to five heteroatoms. The term “heteroatom” refers to nitrogen, oxygen, or sulfur, and includes any oxidized form of nitrogen or sulfur, and any quatemized form of a basic nitrogen. Heteroaryl groups include, without limitation, thienyl, furanyl, pyrrolyl, imidazolyl, pyrazolyl, triazolyl, tetrazolyl, oxazolyl, isoxazolyl, oxadiazolyl, thiazolyl, isothiazolyl, thiadiazolyl, pyridyl, pyridazinyl, pyrimidinyl, pyrazinyl, indolizinyl, purinyl, naphthyridinyl, and pteridinyl. The terms “heteroaryl” and “heteroar-”, as used herein, also include groups in which a heteroaromatic ring is fused to one or more aryl, cycloaliphatic, or heterocyclyl rings, where the radical or point of attachment is on the heteroaromatic ring. Nonlimiting examples include indolyl, isoindolyl, benzothienyl, benzofuranyl, dibenzofuranyl, indazolyl, benzimidazolyl, benzthiazolyl, quinolyl, isoquinolyl, cinnolinyl, phthalazinyl, quinazolinyl, quinoxalinyl, 4H-quinolizinyl, carbazolyl, acridinyl, phenazinyl, phenothiazinyl, phenoxazinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, and pyrido[2,3-b]-l,4-oxazin-3(4H)-one. A heteroaryl group may be monocyclic, bicyclic, bridged bicyclic, or spirocyclic. The term “heteroaryl” may be used interchangeably with the terms “heteroaryl ring,” “heteroaryl group,” or “heteroaromatic,” any of which terms include rings that are optionally substituted. The term “heteroaralkyl” refers to an alkyl group substituted by a heteroaryl, wherein the alkyl and heteroaryl portions independently are optionally substituted. The term “heteroarylenyl” refers to bivalent heteroaryl groups (e.g., pyridylenyl).

[0049]

[0035] As used herein, the terms “heterocycle,” “heterocyclyl,” “heterocyclic radical,” and “heterocyclic ring” are used interchangeably and refer to a stable 5- to 7-membered monocyclic or 7- 10-membered bicyclic heterocyclic moiety that is either saturated or partially unsaturated, and having, in addition to carbon atoms, one or more, preferably one to four, heteroatoms, as defined above. When used in reference to a ring atom of a heterocycle, the

[0050] 331652340 ASCB-018 / 01WO (360511-2180)term "nitrogen" includes a substituted nitrogen. As an example, in a saturated or partially unsaturated ring having 0-3 heteroatoms selected from oxygen, sulfur or nitrogen, the nitrogen may be N (as in 3,4-dihydro-2H-pyrrolyl), NH (as in pyrrolidinyl), or +NR (as in N- substituted pyrrolidinyl).

[0051]

[0036] A heterocyclic ring can be attached to its pendant group at any heteroatom or carbon atom that results in a stable structure and any of the ring atoms can be optionally substituted. Examples of such saturated or partially unsaturated heterocyclic radicals include, without limitation, tetrahydrofuranyl, tetrahydrothiophenyl pyrrolidinyl, piperidinyl, pyrrolinyl, tetrahydroquinolinyl, tetrahydroisoquinolinyl, decahydroquinolinyl, oxazolidinyl, piperazinyl, dioxanyl, dioxolanyl, diazepinyl, oxazepinyl, thiazepinyl, morpholinyl, and quinuclidinyl. The terms “heterocycle,” “heterocyclyl,” “heterocyclyl ring,” “heterocyclic group,” “heterocyclic moiety,” and “heterocyclic radical,” are used interchangeably herein, and also include groups in which a heterocyclyl ring is fused to one or more aryl, heteroaryl, or cycloaliphatic rings, such as indolinyl, 3H-indolyl, chromanyl, phenanthridinyl, or tetrahydroquinolinyl. In some embodiments, a heterocyclic ring may be a 5-12 membered bicyclic, bridged bicyclic, or spirocyclic ring. A heterocyclic ring may include one or more oxo (=0) or thioxo (=S) substituent. The term “heterocyclylalkyl” refers to an alkyl group substituted by a heterocyclyl, wherein the alkyl and heterocyclyl portions independently are optionally substituted.

[0052]

[0037] As used herein, the term “partially unsaturated” refers to a ring moiety that includes at least one double or triple bond. The term “partially unsaturated” is intended to encompass rings having multiple sites of unsaturation, but is not intended to include aryl or heteroaryl moieties, as herein defined.

[0053]

[0038] As described herein, compounds as provided herein may contain “optionally substituted” moieties. In general, the term “substituted”, whether preceded by the term “optionally” or not, means that one or more hydrogens of the designated moiety are replaced with a suitable substituent. Unless otherwise indicated, an “optionally substituted” group may have a suitable substituent at each substitutable position of the group, and when more than one position in any given structure may be substituted with more than one substituent selected from a specified group, the substituent may be either the same or different at every position. Combinations of substituents envisioned are preferably those that result in the formation of stable or chemically feasible compounds. The term “stable,” as used herein, refers to compounds that are not substantially altered when subjected to conditions to allow for their

[0054] 331652340 ASCB-018 / 01WO (360511-2180)production, detection, and, in certain embodiments, their recovery, purification, and use for one or more of the purposes disclosed herein.

[0055]

[0039] Suitable monovalent substituents on a substitutable carbon atom of an “optionally substituted” group are independently halogen; -(CH2)o4R°; -(CH2)o-4OR°; -0-(CH2)O-4C(0)OR°; -(CH2)O4CH(0RO)2; -(CH2)O4SRO; -(CH2)O4Ph, which may be substituted with R°; -(CH2)o40(CH2)o iPh which may be substituted with R°; -CH=CHPh, which may be substituted with R°; -NO2; -CN; -N3; -(CH2)o4N(R°)2; -(CH2)o-4N(RO)C(0)R°; -N(R°)C(S)R°; -(CH2)O-4N(R°)C(0)NR°2; -N(RO)C(S)NR°2; -(CH2)O4N(R°)C(O)OR°; -N(R°)N(R°)C(O)R°; -N(R°)N(R°)C(0)NRO2; -N(R°)N(R°)C(O)OR°; -(CH2)O4C(0)RO; -C(S)R°; -(CH2)O4C(O)OR°; -(CH2)O4C(0)N(RO)2; -(CH2)O4C(O)SR°; -(CH2)O4C(O)OSiR°3; -(CH2)o4OC(O)R°; -OC(0)(CH2)o4SR-, SC(S)SR°; -(CH2)o4SC(O)R°; -(CH2)O4C(0)NRO2; -C(S)NRO2; -C(S)SR°; -SC(S)SR°, -(CH2)O40C(0)NRO2; -C(O)N(OR°)R°; -C(O)C(O)R°; -C(O)CH2C(O)R°; -C(NOR°)R°; -(CH2)o4SSR°; -(CH2)o-4S(O)2R°; -(CH2)O4S(0)20RO; -(CH2)O40S(0)2RO; -S(0)2NRO2; -(CH2)O4S(O)R°; -N(R°)S(O)2NR°2; -N(R°)S(O)2R°; -N(OR°)R°; -C(NH)NRO2; -P(O)2R°; -P(O)R°2; -OP(O)R°2; -OP(O)(OR°)2; SiR°3; - (Ci-4straight or branched alkylene)O-N(R°)2; or -(Ci4straight or branched alkylene)C(O)O-N(R°)2, wherein each R° may be substituted as defined below and is independently hydrogen, C1-8 aliphatic, -CH2Ph, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R°, taken together with their intervening atom(s), form a 3-12-membered saturated, partially unsaturated, or aryl mono- or polycyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, which may be substituted as defined below.

[0056]

[0040] Suitable monovalent substituents on R° (or the ring formed by taking two independent occurrences of R° together with their intervening atoms), are independently halogen, -(CH2)o-2R*, -(haloR*), -(CH2)O2OH, -(CH2)O2OR*, -(CH2)O2CH(OR*)2; -O(haloR’), -CN, -N3, -(CH2)O2C(O)R*, -(CH2)O2C(O)OH, -(CH2)O2C(O)OR*, -(CH2)O-4C(0)N(R°)2; -(CH2)O2SR’, -(CH2)O2SH, -(CH2)O2NH2, -(CH2)O2NHR*, -(CH2)O-2NR*2, -NO2, -SiR*3, -OSiR*3, -C(O)SR* — (Ci-4straight or branched alkylene)C(O)OR*, or -SSR* wherein each R* is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently selected from Ci4aliphatic, -CH2Ph, -0(CH2)o iPh, or a 5-6-membered

[0057] 331652340 ASCB-018 / 01WO (360511-2180)saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents on a saturated carbon atom of R° include =0 and =S.

[0058]

[0041] Suitable divalent substituents on a saturated carbon atom of an “optionally substituted” group include the following: =0, =S, =NNR*2, =NNHC(0)R*, =NNHC(0)0R*, =NNHS(O)2R*, =NR*, =N0R*, - O(C(R*2))230- , or -S(C(R*2))2-3S-, wherein each independent occurrence of R* is selected from hydrogen, Ci-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. Suitable divalent substituents that are bound to vicinal substitutable carbons of an “optionally substituted” group include: -O(CR*2)2-3O-, wherein each independent occurrence of R* is selected from hydrogen, Ci-6 aliphatic which may be substituted as defined below, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0059]

[0042] Suitable substituents on the aliphatic group of R* include halogen, -R*, -(haloR*), -OH, -OR*, -O(haloR’), -CN, -C(O)OH, -C(O)OR’, -NH2, -NHR", -NR’2, or -NO2, wherein each R* is unsubstituted or where preceded by “halo” is substituted only with one or more halogens, and is independently C1-4 aliphatic, -CH2PI1, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0060]

[0043] Suitable substituents on a substitutable nitrogen of an “optionally substituted” group include -R\ -NR^, -C(O)R^, -C(O)OR^, -C(O)C(O)R^, -C(O)CH2C(O)R^, -S(O)2Rt, -S(O)2NRt2, -C(S)NRt2, -C( H)NR^2, or -N(Rt)S(O)2Rt; wherein each R’ is independently hydrogen, C1-6 aliphatic which may be substituted as defined below, unsubstituted -OPh, or an unsubstituted 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur, or, notwithstanding the definition above, two independent occurrences of R1', taken together with their intervening atom(s) form an unsubstituted 3-12-membered saturated, partially unsaturated, or aryl mono- or bicyclic ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0061]

[0044] Suitable substituents on the aliphatic group of R’ are independently halogen, -R*, -(haloR*), -OH, -OR*, -O(haloR’), -CN, -C(O)OH, -C(O)OR*, -NH2, -NHR", -NR*2, or -NO2, wherein each R* is unsubstituted or where preceded by “halo” is substituted only with

[0062] 331652340 ASCB-018 / 01WO (360511-2180)one or more halogens, and is independently Ci-4 aliphatic, -CH2PI1, -0(CH2)o iPh, or a 5-6-membered saturated, partially unsaturated, or aryl ring having 0-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0063]

[0045] As used herein, the term “substantially” refers to the qualitative condition of exhibiting total or near-total extent or degree of a characteristic or property of interest.

[0064]

[0046] The convention of naming ascarosides by a several-letter prefix followed by a pound sign (#) and a number is sometimes used (for example ascr#18). This convention is used in the scientific literature and the skilled artisan will understand that each such name is associated with a specific chemical structure of known composition and will readily apprehend the structure of the molecule referred to using this naming convention. Unless otherwise indicated, all compound identifiers of this format used herein conform to the definitions described in the C. elegans Small Molecule Identifier Database (SMID-DB) maintained at www.smid-db.org / .

[0065]

[0047] The term “pathogen” refers to any bacterium, fungus, oomecyte, virus, nematode (e.g., cyst or root knot nematode) or insect with pathogenic effects on a plant.

[0066] DETAILED DESCRIPTION OF THE INVENTION

[0067]

[0048] Compositions and methods for mitigating the crop damage and / or yield losses caused by bacterial pathogens are provided. This disclosure is directed to the treatment of plants with one or more ascarosides to prevent or lessen the effects of pathogens, particularly bacterial pathogens in monocot crops, and in certain embodiments, to lessen the effects of pathogens of the genus Xanthomonas in rice.

[0068]

[0049] In another aspect, the present disclosure provides compositions comprising an ascaroside, useful for treating crops to reduce damage or yield losses caused by bacterial pathogens.

[0069] Methods

[0070]

[0050] In some embodiments, the present disclosure provides methods for treating monocot plants exposed to or infected with bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In certain embodiments, the present disclosure provides methods for preventing or reducing damage to monocot plants from bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In some embodiments, the present disclosure provides methods for increasing yields of monocot plants exposed to bacterial pathogens, the method comprising applying one or more ascarosides to the plant. In some

[0071] 331652340 ASCB-018 / 01WO (360511-2180)embodiments, the present disclosure provides methods of controlling pathogens of the genus Xanthomonas in rice, the method comprising applying one or more ascarosides to the foliage of the plant.

[0072]

[0051] In certain embodiments, the one or more ascarosides are applied to monocot crop plants . In certain embodiments, the monocot crop plant is rice. In certain embodiments, the monocot crop plant belongs to the genus Oryza.

[0073]

[0052] The one or more ascarosides can be applied to the plant by various means, and the mode of application is not particularly limited. Non-limiting examples of suitable modes of ascaroside application include seed treatment, foliar spray or dusting, application by root dip or drench, application to soil, and application of time-release formulations. In certain embodiments, the one or more ascarosides are applied via foliar spray.

[0074]

[0053] In certain embodiments, provided methods comprise applying one or more ascarosides to the crop at least two times during a growing season (e.g. from 2 to about 6 times). In certain embodiments, the one or more ascarosides are applied to the crop two times. In some embodiments, the one or more ascarosides are applied three times. In some embodiments, the one or more ascarosides are applied four times. In some embodiments, the one or more ascarosides are applied between two and six times. In some embodiments, the one or more ascarosides are applied between two and four times.

[0075]

[0054] The timing and / or mode of each ascaroside application in such methods may vary. In certain embodiments an interval between ascaroside applications is between 5 days and 30 days. In certain embodiments an interval between ascaroside applications is between 5 and 20 days, between 5 and 15 days, between 5 and 10 days, between 6 and 12 days, between 7 and 14 days or between 10 and 20 days. In certain embodiments, the interval between ascaroside applications is about 5 days. In certain embodiments, the interval between ascaroside applications is about 7 days.

[0076]

[0077] certain embodiments, the interval between ascaroside applications is about 10 days. In certain embodiments, the interval between ascaroside applications is about 14 days.

[0078]

[0079] certain embodiments, the interval between ascaroside applications is about 21 days. In certain embodiments, the interval between ascaroside applications is about 28 days.

[0080]

[0055] In certain embodiments, an interval between the first and second ascaroside applications is between 5 days and 30 days. In certain embodiments, an interval between the first and second ascaroside applications is between 5 and 20 days, between 5 and 15 days, between 5 and 10 days, between 6 and 12 days, between 7 and 14 days or between 10 and 20

[0081] 331652340 ASCB-018 / 01WO (360511-2180)days. In certain embodiments, the interval between the first and second ascaroside applications is about 5 days. In certain embodiments, the interval between the first and second ascaroside applications is about 7 days. In certain embodiments, the interval between the first and second ascaroside applications is about 10 days. In certain embodiments, the interval between the first and second ascaroside applications is about 14 days. In certain embodiments, the interval between the first and ascaroside second applications is about 21 days. In certain embodiments, the interval between the first and second ascaroside applications is about 28 days.

[0082]

[0056] In some embodiments, provided methods comprise administering an ascaroside composition comprising one or more ascarosides.

[0083]

[0057] In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of 500 mg of ascaroside per hectare or less. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of 250 mg of ascaroside per hectare or less. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of 100 mg of ascaroside per hectare or less. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of 50 mg of ascaroside per hectare or less. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 1 and about 250 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 1 and about 100 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 10 and about 100 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 10 and about 50 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 10 and about 25 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 20 and about 80 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 10 and about 30 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 30 and about 50 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 50 and about 80 mg of ascaroside per hectare.

[0084] 331652340 ASCB-018 / 01WO (360511-2180)In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of between about 60 and about 100 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of about 12.5 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of about 25 mg of ascaroside per hectare. In certain embodiments, the one or more ascarosides or ascaroside composition is applied to the plants at a rate of about 50 mg of ascaroside per hectare.

[0085]

[0058] In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains 1 mg or less of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains 0.5 mg or less of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains 0.2 mg or less of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains 0.1 mg or less of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.01 and 0.05 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.02 and 0.06 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.04 and 0.08 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.05 and 0.1 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.08 and 0.12 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.10 and 0.20 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.10 and 0.15 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.2 and 0.4 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.4 and 0.8 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.6 and 1.0 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.01 and 0.5 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or

[0086] 331652340 ASCB-018 / 01WO (360511-2180)ascaroside composition applied to the plants contains between 0.01 and 0.25 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains between 0.01 and 0.15 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains about 0.03 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains about 0.07 mg of ascaroside per liter. In certain embodiments, the one or more ascarosides or ascaroside composition applied to the plants contains about 0.13 mg of ascaroside per liter.

[0087]

[0059] In certain embodiments, a provided method comprises applying one or more ascarosides or an ascaroside composition to rice plants, wherein: the one or more ascarosides or an ascaroside composition at is applied to the plants least two times and an ascaroside composition contains 1 mg of ascaroside per liter or less; the amount of ascaroside applied in each application is 250 mg per hectare or less; and an interval between the two applications is between 5 and 30 days.

[0088]

[0060] In certain embodiments, a provided method comprises applying one or more ascarosides or an ascaroside composition to rice plants, wherein: the one or more ascarosides or an ascaroside composition at is applied to the plants least two times and an ascaroside composition contains 1 mg of ascaroside per liter or less; the amount of ascaroside applied in each application is 100 mg per hectare or less; and an interval between the two applications is between 5 and 30 days.

[0089]

[0061] In certain embodiments, a provided method comprises applying one or more ascarosides or an ascaroside composition to rice plants, wherein: the one or more ascarosides or an ascaroside composition is applied to the plants least two times and an ascaroside composition contains 0.5 mg of ascaroside per liter or less; the amount of ascaroside applied in each application is 50 mg per hectare or less; and an interval between the two applications is between 5 and 20 days.

[0090]

[0062] In certain embodiments, a provided method comprises applying one or more ascarosides or an ascaroside composition to rice plants, wherein: the one or more ascarosides or an ascaroside composition at is applied to the plants least two times and an ascaroside composition contains between 0.05 and 0.15 mg of ascaroside per liter; the amount of ascaroside applied in each application is between 10 and 75 mg per hectare; and an interval between the two applications is between 5 and 15 days.

[0091] 331652340 ASCB-018 / 01WO (360511-2180)

[0063] In certain embodiments, provided methods are characterized in that the plants subjected to application with the one or more ascarosides or ascaroside composition suffer less pathogen damage (e.g. a lower incidence and / or severity of pathogens or symptoms caused by pathogens) as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants have a lower severity of bacterial disease caused by Xanthomonas oryzae as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants have a lower severity of Bacterial Leaf Blight symptoms as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants have a lower severity of Bacterial Leaf Streak symptoms as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants have a lower severity of Bacterial Sheath Blight symptoms as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants have a lower severity of Bacterial Rice Blast symptoms as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, the severity of disease symptoms is at least 20% lower than corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, the severity of disease symptoms is at least 30% lower, at least 40% lower, at least 50% lower, at least 60% lower, at least 70% lower, or at least 80% lower than corresponding plants grown under the same conditions but lacking the ascaroside application.

[0092]

[0064] In certain embodiments, the damage by bacterial pathogens is at least 20% lower than corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, the damage by bacterial pathogens is at least 30% lower, at least 40% lower, at least 50% lower, at least 60% lower, at least 70% lower, or at least 80% lower than corresponding plants grown under the same conditions but lacking the ascaroside application.

[0093]

[0065] In certain embodiments, provided methods are characterized in that the plants subjected to application of the one or more ascarosides or ascaroside composition provide higher yields as compared to corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the plants provide yields that are at least 5% higher than corresponding plants grown under the same conditions but lacking the ascaroside application. In certain embodiments, where the plants are rice, the

[0094] 331652340 ASCB-018 / 01WO (360511-2180)plants provide yields that are at least 10% higher, at least 15% higher, at least 20% higher, at least 25% higher, at least 30% higher, or at least 40% higher, than corresponding plants grown under the same conditions but lacking the ascaroside application.

[0095]

[0066] In some embodiments, provided methods comprise application of the one or more ascarosides or ascaroside composition to a plot of monocot plants in the field (i.e., not within a laboratory setting). In some embodiments, provided methods comprise application of the one or more ascarosides or ascaroside composition to a plot of monocot plants to a plot of least 6m x 4m. In some embodiments, provided methods comprise application of the one or more ascarosides or ascaroside composition to a plot of monocot plants to a plot of least one acre.

[0096]

[0067] In some embodiments, provided methods are characterized in that the first treatment with ascaroside occurs between 0 and 2 weeks after transplant of the plant. In some embodiments, provided methods are characterized in that the first treatment with ascaroside occurs between 2 and 4 weeks after transplant of the plant.

[0097] Ascarosides

[0098]

[0068] Ascarosides suitable for the methods described herein are derivatives of the sugar ascarylose — a di -deoxy sugar lacking hydroxyl groups at its 3- and 6-positions. Such ascarosides have the general structure shown in Formula I:

[0099]

[0100] (Formula I),

[0101] or salts thereof, wherein:

[0102] Z is an optionally unsaturated, optionally substituted C2-40 aliphatic group, optionally terminating in a chain end comprising a nitrogen-, oxygen-, or sulfur containing functional group, and

[0103] each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group, a sulfur-linked functional group, a silicon-linked functional group, a C2-20 carbonate (e.g., -a moiety -C(O)ORC), a C2 -20 carbamate (e.g., -a moiety -C(O)N(RC)2), a C2-20 thioester (e.g., a moiety -C(S)RC), a C2-20 thiocarbonate (e.g., a moiety -C(S)ORC), a C2-20 dithiocarbonate (e.g., a moiety -C(S)SRC), a C1-20 thiocarbamate (e.g., a

[0104] 331652340 ASCB-018 / 01WO (360511-2180)moiety -C(S)N(RC)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule, where each Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon- containing linker moiety to another ascaroside molecule, and where Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation.

[0105]

[0069] In certain embodiments, Z is:

[0106] (i) -CH(CH3)-R1, where R1is an optionally substituted C1-40 aliphatic group;

[0107] (ii) -CH(CH3)-(CH2)n-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted Ci- 20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0108] (iii) -CH(CH3)-(CH2)n-CH=CH-CC>2R2, where n is an integer from 1 to 40, and R2is - H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0109] (iv) -CH(CH3)-(CH2)n-CH(OH)-CH2-CC>2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0110] (v) -CH(CH3)-(CH2)n-C(O)-CH2-CC>2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a

[0111] 331652340 ASCB-018 / 01WO (360511-2180)nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0112] (vi) - (CH2)n- CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0113] (vii) -(CH2)n-CH=CH-CC>2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted Ci- 20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0114] (viii) -(CH2)n-CH(OH)-CH2-CChR2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or

[0115] (ix) -(CH2)n-C(O)-CH2-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted Ci- 20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.

[0116]

[0070] In certain embodiments, Z is:

[0117] (x) -CH(CH3)-(CH2)n-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0118] 331652340 ASCB-018 / 01WO (360511-2180)(xi) -CH(CH3)-(CH2)n-CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0119] (xii) -CH(CH3)-(CH2)n-CH(OH)-CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0120] (xiii) -CH(CH3)-(CH2)n-C(O)-CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0121] (xiv) -(CH2)n-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0122] (xv) -(CH2)n-CH=CH-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0123] (xvi) -(CH2)n-CH(OH)-CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an

[0124] 331652340 ASCB-018 / 01WO (360511-2180)optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule;

[0125] (xvii) -(CH2)n-C(O)-CH2-CON(R3)2, where n is an integer from 1 to 40, and each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule; or

[0126] (xviii) an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising a nitrogen-, oxygen- or sulfur-containing functional group.

[0127]

[0071] As defined above and described herein, Z is an optionally unsaturated, optionally substituted C2-40 aliphatic group, optionally terminating in a chain end comprising a nitrogen-, oxygen-, or sulfur containing functional group. In some embodiments, Z comprises a nitrogen-, oxygen-, or sulfur-containing functional group. It will be appreciated that “an oxygencontaining functional group” refers to moieties that comprise one or more oxygen atoms (e.g., carbonyl-containing groups such as esters, aldehydes, carboxylic acids, and ketones; ethers, hydroxyls, and heterocyclic rings comprising one or more oxygen atoms and / or one of the foregoing functional groups); “a nitrogen-containing functional group” refers to moieties that comprise one or more nitrogen atoms (e.g., amines, amides, carbamates, imines, ureas, oximes, amidines, guanidines, nitriles, azo groups, azides, and heterocyclic rings comprising one or more nitrogen atoms and / or one of the foregoing functional groups); and “a sulfur-containing functional group” refers to moieties that comprise one or more sulfur atoms (e.g., thioether, sulfone, sulfonic acid, sulfoxide, thiol, thiocyanate, or disulfide).

[0128]

[0072] In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an oxygen-containing functional group. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising a carboxylic acid. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an aldehyde. In certain embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an ester. In some embodiments, Z an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -CO2R2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end

[0129] 331652340 ASCB-018 / 01WO (360511-2180)comprising -CO2H. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -CO2CH3. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -CON(R3)2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising -N(R3)2. In some embodiments, Z is an optionally unsaturated, optionally substituted C2-40 sidechain terminating in a chain end comprising an ester comprising a linker moiety covalently attached to one or more additional ascaroside molecules.

[0130]

[0073] As described above, the ascarylose sugar moiety in the provided compounds can be substituted or unsubstituted (z.e., there can be functional groups other than -OH at 2- and 4-positions of the sugar or, stated differently, variables Raand / or Rbcan be other than -H in any of the formulae herein).

[0131]

[0074] As defined above and described herein, each of Raand Rbis independently -H, or an optionally substituted moiety selected from the group consisting of: C1-20 aliphatic, C1-20 acyl, C1-20 heteroaliphatic, aryl, heteroaryl, a hydroxyl protecting group, a phosphorous-linked functional group, a sulfur-linked functional group, a silicon-linked functional group, a C2-20 carbonate (e.g., -a moiety -C(O)ORC), a C2-20 carbamate (e.g., -a moiety -C(O)N(RC)2), a C2-20 thioester (e.g. a moiety -C(S)RC), a C2-20 thiocarbonate (e.g. a moiety -C(S)ORC), a C2-20 dithiocarbonate (e.g. a moiety -C(S)SRC), a C1-20 thiocarbamate (e.g. a moiety -C(S)N(RC)2), a sugar moiety, a peptide, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule.

[0132]

[0075] In certain embodiments, Rais -H. In certain embodiments, Rbis -H. In certain embodiments, Raand Rbare the same. In certain embodiments Raand Rbare both -H. In certain embodiments, Raand Rbare different. In certain embodiments, Rais -H, and Rbis other than -H. In certain embodiments, Rais other than -H and Rbis -H. In certain embodiments, Rais -H and Rbis -hydroxy benzoate. In certain embodiments, Rais -H and Rbis indole-3 -carboxylate. In certain embodiments, Rais -H and Rbis (E)-2 -methyl -2 -butenoate. In certain embodiments, Rais -H and Rbis picolinate. In certain embodiments, Rais -H and Rbis nicotinate. In certain embodiments, Rais -H and Rbis (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)amino)-4-oxobutanoate. In certain embodiments, Rais -H and Rbis 4-((4-hydroxyphenethyl)amino)-4-oxobutanoate. In certain embodiments, Racomprises a glycoside, amino acid, a peptide, or nucleotide. In certain embodiments, Rbcomprises a glycoside, amino acid, a peptide, or nucleotide. In certain embodiments, Racomprises a linkage to a second ascaroside molecule.

[0133] 331652340 ASCB-018 / 01WO (360511-2180)In certain embodiments, Rbcomprises a linkage to an ascaroside molecule. In certain embodiments, Racomprises a sugar. In certain embodiments, Rbcomprises a sugar.

[0134]

[0076] In some embodiments, Rais an optionally substituted C1-20 aliphatic. In some embodiments, Rais an optionally substituted C1-6 aliphatic. In some embodiments, Rais C1-20 aliphatic. In some embodiments, Rais C1-6 aliphatic. In some embodiments, Rais methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, ort-butyl. In some embodiments, Rais C1-20 acyl. In some embodiments, Rais -C(O)RC. In some embodiments, Rais -C(O)H. In some embodiments, Rais -C(O)CH3. In some embodiments, Rais an optionally substituted Ci-20 heteroaliphatic. In some embodiments, Rais an optionally substituted C1-6 heteroaliphatic. In some embodiments, Rais C1-20 heteroaliphatic. In some embodiments, Rais C1-6 heteroaliphatic. In some embodiments, Rais an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais optionally substituted aryl. In some embodiments, Rais optionally substituted phenyl. In some embodiments, Rais phenyl. In some embodiments, Rais an optionally substituted heteroaryl group. In some embodiments, Rais an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rais an optionally substituted C2-20 carbonate. In some embodiments, Rais -C(O)ORC. In some embodiments, Rais an optionally substituted C2-20 carbamate. In some embodiments, Rais -C(O)N(RC)2. In some embodiments, Rais an optionally substituted C2-20 thioester. In some embodiments, Rais -C(S)RC. In some embodiments, Rais an optionally substituted C2-20 thiocarbonate. In some embodiments, Rais -C(S)ORC. In some embodiments, Rais an optionally substituted C2-20 dithiocarbonate. In some embodiments, Rais -C(S)SRC. In some embodiments, Rais an optionally substituted C 1-20 thiocarbamate. In some embodiments, Rais -C(S)N(RC)2.

[0135]

[0077] In some embodiments, Rais an optionally substituted hydroxyl protecting group. Suitable hydroxyl protecting groups are well known in the art and include those described in detail in Protecting Groups in Organic Synthesis, T. W. Greene and P. G. M. Wuts, 3rdedition, John Wiley & Sons, 1999. Examples of suitable oxygen protecting groups include, but are not

[0136] 331652340 ASCB-018 / 01WO (360511-2180)limited to, acetyl, benzoyl benzyl, P-methoxyethoxymethyl ether (MEM), dimethoxytrityl (DMT), methoxymethyl ether (MOM), methoxytrityl (MMT), p-methoxybenzyl ether (PMB), methylthiomethyl ether, pivaloyl, tetrahydropyranyl (THP), tetrahydrofuran (THF), trityl, silyl ethers (e.g., trimethylsilyl (TMS), tert-butyldimethylsilyl (TBDMS), tri-iso-propylsilyloxymethyl (TOM), and triisopropylsilyl (TIPS) ethers), methyl ethers, and ethoxyethyl ethers. In some embodiments, Rais -ORC.

[0137]

[0078] In some embodiments, Rais an optionally substituted phosphorous-linked functional group. It will be appreciated that “phosphorous-linked functional group” as used herein refers to moieties that comprise one or more phosphorous atoms (e.g., phosphine, phosphodiester, phosphonic acid, phosphate). In some embodiments, Rais an optionally substituted sulfur-linked functional group. It will be appreciated that “sulfur-linked functional group” as used herein refers to moieties that comprise one or more sulfur atoms (e.g., thioether, sulfone, sulfonic acid, sulfoxide, thiol, thiocyanate, or disulfide). In some embodiments, Rais an optionally substituted silicon-linked functional group. It will be appreciated that “silicon-linked functional group” as used herein refers to moieties that comprise one or more silicon atoms (e.g., silanol, suloxides, siloxanes, silyl ethers, silyl chlorides, silyl hydrides, silenes, or siloles).

[0138]

[0079] In some embodiments, Rais an optionally substituted sugar moiety. In some embodiments, Rais an optionally substituted peptide. In some embodiments, Rais an optionally substituted polymer chain. In some embodiments, Rais a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule. In some embodiments, Rais an optionally substituted Ci-6 aliphatic or heteroaliphatic comprising an ascaroside.

[0139]

[0080] In some embodiments, Rbis an optionally substituted C1-20 aliphatic. In some embodiments, Rbis an optionally substituted C1-6 aliphatic. In some embodiments, Rbis C1-20 aliphatic. In some embodiments, Rbis C1-6 aliphatic. In some embodiments, Rbis methyl, ethyl, n-propyl, iso-propyl, n-butyl, isobutyl, sec-butyl, or t-butyl. In some embodiments, Rbis C1-20 acyl. In some embodiments, Rbis -C(O)RC. In some embodiments, Rbis -C(O)H. In some embodiments, Rbis -C(O)CH3. In some embodiments, Rbis an optionally substituted Ci-20 heteroaliphatic. In some embodiments, Rbis an optionally substituted C1-6 heteroaliphatic. In some embodiments, Rbis C1-20 heteroaliphatic. In some embodiments, Rbis C1-6 heteroaliphatic. In some embodiments, Rbis an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted 8- and

[0140] 331652340 ASCB-018 / 01WO (360511-2180)12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis optionally substituted aryl. In some embodiments, Rbis optionally substituted phenyl. In some embodiments, Rbis phenyl. In some embodiments, Rbis an optionally substituted heteroaryl group. In some embodiments, Rbis an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rbis an optionally substituted C2-20 carbonate. In some embodiments, Rbis -C(O)ORC. In some embodiments, Rbis an optionally substituted C2-20 carbamate. In some embodiments, Rbis -C(O)N(RC)2. In some embodiments, Rbis an optionally substituted C2-20 thioester. In some embodiments, Rbis -C(S)RC. In some embodiments, Rbis an optionally substituted C2-20 thiocarbonate. In some embodiments, Rbis -C(S)ORC. In some embodiments, Rbis an optionally substituted C2-20 dithiocarbonate. In some embodiments, Rbis -C(S)SRC. In some embodiments, Rais an optionally substituted C 1-20 thiocarbamate. In some embodiments, Rbis -C(S)N(RC)2.

[0141]

[0081] In some embodiments, Rbis an optionally substituted hydroxyl protecting group.

[0142]

[0082] In some embodiments, Rbis an optionally substituted phosphorous-linked functional group. In some embodiments, Rbis an optionally substituted sulfur-linked functional group. In some embodiments, Rbis an optionally substituted silicon-linked functional group.

[0143]

[0083] In some embodiments, Rbis an optionally substituted sugar moiety. In some embodiments, Rais an optionally substituted peptide. In some embodiments, Rbis an optionally substituted polymer chain. In some embodiments, Rbis a linkage via a bond or a carbon-containing linker moiety to an ascaroside molecule. In some embodiments, Rbis an optionally substituted C1-6 aliphatic or heteroaliphatic comprising an ascaroside.

[0144]

[0084] In some embodiments, Raand Rbmay be taken together to form an optionally substituted ring, optionally containing one or more heteroatoms, and optionally containing one or more sites of unsaturation. In some embodiments, Raand Rbmay be taken together to form an optionally substituted 3- to 12- membered monocyclic or bicyclic saturated or partially unsaturated carbocyclyl or heterocyclyl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Raand Rbmay be taken together to form an optionally substituted 5- to 12-membered monocyclic or bicyclic aryl or heteroaryl ring having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0145] 331652340 ASCB-018 / 01WO (360511-2180)

[0085] As defined above and described herein, each Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl, a polymer chain, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule.

[0146]

[0086] In some embodiments, Rcis independently at each occurrence selected from -H, optionally substituted C1-12 aliphatic, optionally substituted C1-12 heteroaliphatic, optionally substituted aryl, optionally substituted heteroaryl.

[0147]

[0087] In some embodiments, an occurrence of Rcis -H. In some embodiments, Rcis an optionally substituted C1-12 aliphatic group. In some embodiments, Rcis an optionally substituted C1-6 aliphatic group. In some embodiments, Rcis an optionally substituted C1-12 heteroaliphatic group. In some embodiments, Rcis an optionally substituted C1-6 heteroaliphatic group. In some embodiments, Rcis an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted aryl group. In some embodiments, Rcis optionally substituted phenyl. In some embodiments, Rcis phenyl. In some embodiments, Rcis an optionally substituted heteroaryl group. In some embodiments, Rcis an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, Rcis an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0148]

[0088] As defined above and described herein, R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a glycoside, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, R2is -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, or an optionally substituted heteroaryl group.

[0149]

[0089] In some embodiments, R2is -H. In some embodiments, R2is a metal cation. In some embodiments, R2is an optionally substituted C1-20 aliphatic group. In some embodiments, R2is an optionally substituted C1-6 aliphatic group. In some embodiments, R2is an optionally

[0150] 331652340 ASCB-018 / 01WO (360511-2180)substituted C1-20 heteroaliphatic group. In some embodiments, R2is an optionally substituted C1-6 heteroaliphatic group. In some embodiments, R2is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted aromatic group. In some embodiments, R2is optionally substituted phenyl. In some embodiments, R2is phenyl. In some embodiments, R2is an optionally substituted heteroaryl group. In some embodiments, R2is an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R2is an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0151]

[0090] In some embodiments, R2is a glycoside. It will be appreciated that a glycoside refers to a moiety comprising a sugar bound to another functional group via a glycosidic bond.

[0152]

[0091] In some embodiments, R2is nucleotide. In some embodiments, R2is adenosine monophosphate, cytidine monophosphate, guanosine monophosphate, or uridine monophosphate. In some embodiments, R2is deoxyadenosine monophosphate, deoxy cytidine monophosphate, deoxyguanosine monophosphate, or deoxythymidine monophosphate.

[0153]

[0092] In some embodiments, R2is a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, R2is an optionally substituted C1-6 aliphatic or heteroaliphatic comprising an ascaroside.

[0154]

[0093] As defined above and described herein, each R3is independently -H, an optionally substituted C1-20 aliphatic group, an optionally substituted C1-20 heteroaliphatic group, an optionally substituted aromatic group, an optionally substituted heteroaryl group, a polymer chain, an amino acid, a peptide, a nucleotide, or a linkage via a bond or a carbon-containing linker moiety to another ascaroside molecule. In some embodiments, each R3is independently selected from -H and C1-8 aliphatic. In some embodiments, one R3is -H and the other R3is other than -H. In some embodiments, neither R3is -H. In some embodiments, each R3is -H. In some embodiments, an occurrence of R3is an optionally substituted C1-20 aliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-6 aliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-20 heteroaliphatic group. In some embodiments, an occurrence of R3is an optionally substituted C1-6 heteroaliphatic

[0155] 331652340 ASCB-018 / 01WO (360511-2180)group. In some embodiments, R3is an optionally substituted 3- and 8-membered saturated or partially unsaturated heterocyclyl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3is an optionally substituted 8- and 12-membered saturated or partially unsaturated bicyclic heterocyclyl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, occurrence of R3is an optionally substituted aryl group. In some embodiments, R3is optionally substituted phenyl. In some embodiments, R3is phenyl. In some embodiments, R3is an optionally substituted heteroaryl group. In some embodiments, R3is an optionally substituted 5- to 6-membered heteroaryl having 1-3 heteroatoms independently selected from nitrogen, oxygen, or sulfur. In some embodiments, R3is an optionally substituted 8- to 12-membered heteroaryl having 1-4 heteroatoms independently selected from nitrogen, oxygen, or sulfur.

[0156]

[0094] In certain embodiments, Raand Rbare the same. In certain embodiments Raand Rbare both -H.

[0157]

[0095] In certain embodiments, Raand Rbare different. In certain embodiments, Rais -H, and Rbis other than -H. In certain embodiments, Rais other than -H and Rbis -H. In certain embodiments, Rais -H and Rbis -hydroxy benzoate. In certain embodiments, Rais -H and Rbis indole-3 -carboxylate. In certain embodiments, Rais -H and Rbis (E)-2-methyl-2-butenoate. In certain embodiments, Rais -H and Rbis picolinate. In certain embodiments, Rais -H and Rbis nicotinate. In certain embodiments, Rais -H and Rbis (R)-2-hydroxy-2-(4-hydroxyphenyl)ethyl)amino)-4-oxobutanoate. In certain embodiments, Rais -H and Rbis 4-((4-hydroxyphenethyl)amino)-4-oxobutanoate.

[0158]

[0096] In certain embodiments Raand Rbare both -H, and Z is selected from the formulae defined in (i) to (xvii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (i) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (ii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (iii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (iv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (v) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (vi) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (vii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (viii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (ix) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (x) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xi) above. In certain

[0159] 331652340 ASCB-018 / 01WO (360511-2180)embodiments Raand Rbare both -H, and Z conforms to formula (xii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xiii) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xiv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xv) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xvi) above. In certain embodiments Raand Rbare both -H, and Z conforms to formula (xvii) above

[0160]

[0097] In certain embodiments, R2is -H. In certain embodiments, R2is a metal cation. In certain embodiments, R2is an organic cation (e.g., a nitrogen- or phosphorous-centered cationic group). In certain embodiments, R2is an optionally substituted C1-20 aliphatic group. In certain embodiments, R2is an optionally substituted C1-12 aliphatic group. In certain embodiments, R2is an optionally substituted C1-8 aliphatic group. In certain embodiments, R2is an optionally substituted C1-6 aliphatic group. In certain embodiments, R2is selected from methyl, ethyl, w-propyl. z-propyl, w-butyl. scc-butyl. and / -butyl. In certain embodiments, R2is an optionally substituted aromatic group. In certain embodiments, R2is a glycoside. In certain embodiments, R2comprises an amino acid. In certain embodiments, R2comprises a peptide. In certain embodiments, R2comprises a nucleotide.

[0161]

[0098] In certain embodiments, at least one R3is -H. In certain embodiments, both R3groups are -H. In certain embodiments, at least one R3is an optionally substituted C1-20 aliphatic group. In certain embodiments, both R3groups are an optionally substituted C1-20 aliphatic group which may be the same or different. In certain embodiments, at least one R3is an optionally substituted C1-12 aliphatic group. In certain embodiments, at least one R3is an optionally substituted C1-8 aliphatic group. In certain embodiments, at least one R3is an optionally substituted C1-6 aliphatic group. In certain embodiments, at least one R3is selected from methyl, ethyl, w-propyl. z-propyl, w-butyl. scc-butyl. and / -butyl. In certain embodiments, at least one R3is -CH2CH2OH. In certain embodiments, at least one R3is -CH2CH2OR2, where R2is as defined in the genera and subgenera herein. In certain embodiments, at least one R3is an optionally substituted aromatic group. In certain embodiments, at least one R3comprises a glycoside. In certain embodiments, at least one R3comprises an amino acid. In certain embodiments, at least one R3at least one R3comprises a peptide. In certain embodiments, at least one R3comprises a nucleotide.

[0162]

[0099] In certain embodiments, an ascaroside is selected from the group consisting of:

[0163] 331652340 ASCB-018 / 01WO (360511-2180)

[0164]

[0165] where x is an integer from 1 to 22, and each of Ra, Rb, and R2is as defined above and in the genera and subgenera herein.

[0166]

[0100] In certain embodiments, an ascaroside is selected from the group consisting of:

[0167]

[0168] where each of x, Ra, and Rb, is as defined above and in the genera and subgenera herein.

[0169]

[0101] In certain embodiments, an ascaroside is selected from the group consisting of:

[0170]

[0171] where y is an integer from 1 to 20, and each of Ra, Rb, and R2is as defined above and in the genera and subgenera herein.

[0172]

[0102] In certain embodiments, an ascaroside is selected from the group consisting of:

[0173]

[0174] where each of i’. Ra, and Rb, is as defined above and in the genera and subgenera herein.

[0175]

[0103] In certain embodiments, an ascaroside is selected from the group consisting of:

[0176]

[0177] where x is an integer from 1 to 22, and R2is as defined above and in the genera and subgenera herein.

[0178]

[0104] In certain embodiments, an ascaroside is selected from the group consisting of:

[0179] 331652340 ASCB-018 / 01WO (360511-2180)

[0180]

[0181] where x is as defined above and in the genera and subgenera herein.

[0182]

[0105] In certain embodiments, an ascaroside is selected from the group consisting of:

[0183]

[0184] where y is an integer from 1 to 20, and R2is as defined above and in the genera and subgenera herein.

[0185]

[0106] In certain embodiments, an ascaroside is selected from the group consisting of:

[0186]

[0187] where y is as defined above and in the genera and subgenera herein.

[0188]

[0107] In certain embodiments, an ascaroside is selected from the group consisting of:

[0189] >< <

[0190]

[0191] where x is an integer from 1 to 22, and each of Ra, Rb, and R3is as defined above and in the genera and subgenera herein.

[0192]

[0108] In certain embodiments, an ascaroside is selected from the group consisting of:

[0193] <

[0194]

[0195] where each of x and R3is as defined above and in the genera and subgenera herein.

[0196]

[0109] In certain embodiments, an ascaroside is selected from the group consisting of:

[0197] 331652340 ASCB-018 / 01WO (360511-2180)

[0198]

[0199] where y is an integer from 1 to 20, and each of Ra, Rb, and R3is as defined above and in the genera and subgenera herein.

[0200]

[0110] In certain embodiments, an ascaroside is selected from the group consisting of:

[0201]

[0202] where each of i’ and R3is as defined above and in the genera and subgenera herein.

[0203] [Hl] In an embodiment, ascarosides useful in the context of the present disclosure have the general structure (I), where Z is -CH(CH3)-(CH2)n-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide, and can be used for inhibiting human pathogenic bacterial growth in or on a plant.

[0204]

[0112] In an embodiment, ascarosides useful in the context of the present disclosure have the general structure (I) where Z is -CH(CH3)-(CH2)n-CH=CH-CO2R2, where n is an integer from 1 to 40, and R2is -H, a metal cation, an optionally substituted C1-20 aliphatic group, an optionally substituted aromatic group, a glycoside, an amino acid, a peptide, or a nucleotide.

[0205]

[0113] Specific ascarosides that are useful in the context of the present disclosure include, but are not limited to, ascr#7 and ascr#18.

[0206]

[0207]

[0114] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#9, ascr#12, ascr#14, ascr#l, ascrtflO, ascr#16, ascr#18, ascr#20, ascr#22, ascr#24, ascr#26, ascr#28, ascr#30, ascr#32, ascr#34, and ascr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: ascrtflO, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24. In certain

[0208] 331652340 ASCB-018 / 01WO (360511-2180)embodiments, an ascaroside used in the provided methods is selected from the group consisting of: ascr#9, ascr#14, ascrtflO, and ascr#18.In certain embodiments, an ascaroside used in the provided methods is ascr#18.

[0209]

[0115] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#5, oscr#9, oscr#12, oscrtfl, oscr#14, oscrtflO, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: oscrtflO, oscr#16, oscr#18, oscr#20, and oscr#22. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: bhas#5, oscr#9, oscr#12, oscrtfl, oscr#14, oscrtflO, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36. In certain embodiments, an ascaroside used in the provided methods is selected from the group consisting of: oscr#10, oscr#16, oscr#18, oscr#20, and oscr#22.

[0210]

[0116] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhas#9, bhas#10, bhas#16, bhas#18, bhas#22, bhas#24, bhas#26, bhas#28, bhas#30, bhas#32, bhas#34, bhas#36, bhas#38, bhas#40, and bhas#42.

[0211]

[0117] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: bhos#10, bhos#16, bhos#18, bhos#22, bhos#24, bhos#26, bhos#28, bhos#30, bhos#32, bhos#34, bhos#36, bhos#38, bhos#40, and bhos#42.

[0212]

[0118] In certain embodiments, an ascaroside used in the provided methods and compositions is selected from the group consisting of: ascr#18, oscr#16, oscr#17, oscr#15, bhas#18, bhos#16, glas#18, dhas#18, ibha#18, ibho#16, icas#18, icos#15, icos#16, and any combination of two or more of these.

[0213]

[0119] In some embodiments, an ascaroside used in the provided methods and compositions is an ascaroside salt as disclosed in international publication number W02023 / 220174, filed May 10, 2023 or an ascaroside modified to provide for extended release of the active ingredient as disclosed in international publication number WO2023 / 212362, filed April 28, 2023, both of which are incorporated by reference herein in their entireties.

[0214]

[0120] Ascarosides can be obtained from natural sources (e.g., nematodes) or they may be prepared synthetically. Ascarosides can be prepared synthetically, for example, by converting 1 -O-substi tuted rhamnose to I -^-substituted ascarylose. An exemplary method of preparing ascarosides includes: providing as a feedstock a 1 -^-substituted rhamnose; forming a mono-

[0215] 331652340 ASCB-018 / 01WO (360511-2180)sulfonate ester at the 3-OH group of the feedstock; and treating the mono-sulfonate ester with a hydride source to form a I - / / -substituted ascarylose. In certain embodiments, forming the mono-sulfonate ester is conducted on a substrate without hydroxyl protecting groups at the 2-or 4-position of the rhamnose feedstock. In certain embodiments, such methods comprise contacting the feedstock with a sulfonating agent (i.e., a sulfonyl halide, sulfonic anhydride or similar reagent) in the presence of a Lewis acid. Specific details regarding the synthesis of 1-O-substituted ascarylose can be found in PCT Application Publication No. W 0 / 2022 / 024067, which is incorporated herein by reference.

[0216] Compositions

[0217]

[0121] In some embodiments, the present methods comprise applying a composition comprising one or more ascarosides, also described as an ascaroside composition.

[0218]

[0122] In some embodiments, a composition further comprises one or more agrichemicals. In certain embodiments, agrichemicals include materials present in formulations but not classified as “active ingredients”, these inert ingredients include materials such as solvents, surfactants, wetting agents, stabilizers, compatibilizers, dyes, preservatives, and the like. One or more inert ingredients, e.g., one or more agronomically acceptable carriers (also referred to as agriculturally acceptable or suitable adjuvants) are generally included within agrichemical formulations. The term “agronomically acceptable carrier” includes any carrier suitable for administration to a plant or soil, e.g., customary excipients in formulation techniques, such as used to form solutions (e.g., directly sprayable or dilutable solutions), emulsions, (e.g., emulsion concentrates and diluted emulsions), wettable powders, suspensions, soluble powders, powders, dusts, pastes, soluble powders, granules, suspension-emulsion concentrates, encapsulation into polymeric materials, coatable pastes, natural and synthetic materials impregnated with active compound and microencapsulations in polymeric substances. In some embodiments, agronomically acceptable carriers can include surfactants, emulsifiers, oils, salts, and the like.

[0219]

[0123] Agrichemical compositions can include one or more agronomically acceptable carriers, such as liquid solvents or solid carriers. Other agrichemicals include, but are not limited to, surfactants, including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., silica), cross-linking agents, antioxidants, anti-foaming agents, buffers, pH modifiers,

[0220] 331652340 ASCB-018 / 01WO (360511-2180)compatibility agents, drift control additives, extenders / stickers, tackifiers, plant penetrants, spreaders, wetting agents, and the like. In some embodiments, agrichemicals include wetting agents, emulsifiers, spreaders, and the like. Agrichemical formulations include concentrated versions, in which the agrichemical is present in a concentration of from 2% to 98.0%, with the remaining content being agronomically acceptable carriers / adjuvants.

[0221]

[0124] Such formulations, especially those with less than 50 percent of the agrichemical, can sometimes be used directly, but these formulations can also be diluted with other agronomically acceptable carriers to form more dilute treating formulations.

[0222]

[0125] Agrichemicals may include “adjuvant surfactants” to enhance deposition, wetting, and penetration of the compounds onto the target crop and organism. Adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic 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- C16) ethoxylate; di -sec-butylphenol EO-PO block copolymer; poly siloxane -methyl cap; nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99.

[0223]

[0126] Agrichemicals may also include oil-in-water emulsions. In some embodiments, agrichemicals include organic solvents (i.e. an organic solvent that may be incorporated as an auxiliary liquid solvent in an agrichemical formulation). Suitable liquid solvents include, for example, aromatics (e.g., xylene, toluene and alkylnaphthalenes); chlorinated aromatics or chlorinated aliphatic hydrocarbons (e.g., chlorobenzenes, chloroethylenes and methylene chloride); aliphatic hydrocarbons (e.g., cyclohexane); paraffins (e.g., petroleum fractions, mineral and vegetable oils); alcohols (e.g., butanol or glycol and their ethers and esters); ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone) and strongly polar solvents (e.g., dimethylformamide and dimethyl sulfoxide). Other examples of organic solvents include, but are not limited to, 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

[0224] 331652340 ASCB-018 / 01WO (360511-2180)such as mineral oil, aromatic solvents, paraffinic oils, and the like; terpenic solvents, rosin derivatives, aliphatic ketones such as cyclohexanone, complex aliphaticand 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 certain emulsifiable concentrates. 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.

[0225]

[0127] In some embodiments, agrichemicals comprise solid carriers include, for example, ammonium salts and ground natural minerals (e.g., kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth); ground synthetic minerals (e.g., highly disperse silica, alumina and silicates); crushed and fractionated natural rocks (e.g., calcite, marble, pumice, sepiolite and dolomite); synthetic granules of inorganic and organic meals; granules of organic material (e.g., sawdust, coconut shells, maize cobs and tobacco stalks). In some embodiments, dry compositions can comprise powders and the like.

[0226]

[0128] In some embodiments, agrichemicals comprise emulsifiers and foam-formers, for example, nonionic and anionic emulsifiers (e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example, alkylaryl polyglycol ethers, alkylsulfonates, alkyl sulphates and arylsulfonates) protein hydrolysates.

[0227]

[0129] In some embodiments, agrichemicals comprise dispersants, for example, lignin-sulfite waste liquors and methylcellulose. In some embodiments, agrichemicals comprise tackifiers such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or lattices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, as well as natural phospholipids, such as cephalins and lecithins, and synthetic phospholipids. In some embodiments, agrichemicals comprise nonionic emulsifiers, these can 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. In some embodiments, agrichemicals comprise cationic emulsifiers including quaternary ammonium compounds and fatty amine salts. In some embodiments, agrichemicals comprise anionic

[0228] 331652340 ASCB-018 / 01WO (360511-2180)emulsifiers including the oil soluble salts (e.g., calcium) of alkylaryl sulphonic acids, oilsoluble salts or sulfated polyglycolethers and appropriate salts of phosphated- polyglycol ether.

[0229]

[0130] In some embodiments, agrichemicals comprise surfactants such as sulfonated lignins, condensed naphthalene-sulfonates, the naphthalene sulfonates, alkyl-benenesulfonates, alky sulfonates or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof.

[0230]

[0131] In some embodiments, agrichemicals comprise colorants such as inorganic pigments, for example, iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs and metal phthalocyanine dyestuffs, and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc may also be included in the agrichemicals.

[0231]

[0132] In certain embodiments, agrichemicals are defined as any substance or formulation intended for application to a plant characterized in that its application to the plant causes some degree of phytotoxic damage to the plant. In certain embodiments, such phytotoxic effects are selected from the group consisting of: poor germination; death of seedlings; death or damage to rapidly growing succulent tissues; stunting or delayed plant development; misshaped or distorted plants, fruits, or leaves; russeting or bronzing of leaves or fruit; dead spots or flecks on leaves; dead leaf tips or leaf margins; dead areas between the veins of the leaves; and combinations of any two or more of these.

[0232]

[0133] In certain embodiments, the provided compositions are characterized in that they contain a very low concentration of ascaroside. For example, less than 1.0 or 0.5 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains less than 0.2 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains less than 0.1 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.01 and 0.05 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.02 and 0.06 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.04 and 0.08 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.05 and 0.1 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.08 and 0.12 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.10 and 0.20 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.2 and 0.4 mg of ascaroside per liter. In certain

[0233] 331652340 ASCB-018 / 01WO (360511-2180)embodiments, the provided ascaroside composition contains between 0.4 and 0.8 mg of ascaroside per liter. In certain embodiments, the provided ascaroside composition contains between 0.6 and 1.0 mg of ascaroside per liter.

[0234]

[0134] As noted above, in some embodiments, provided methods comprise application of one or more ascarosides in combination with other agrichemicals such as an antimicrobial agent (e.g., including, but not limited to, triazole, strobilurin, or SDHI fungicides; contact fungicides such as copper, mancozeb or chlorothalonil; and antibacterial compounds). In certain embodiments, provided methods comprise application of one more or ascarosides in combination with a copper compound (e.g. copper sulfate, copper oxychloride, or copper hydroxide).

[0235]

[0135] In some embodiments, provided methods comprise applying one or more ascarosides and picoxystrobin. In some embodiments, picoxystrobin is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application). In some embodiments, picoxystrobin is applied at about 150 g per hectare.

[0236]

[0136] In some embodiments, provided methods comprise applying one or more ascarosides and difenoconazole. In some embodiments, difenoconazole is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application). In some embodiments, difenoconazole is applied at about 63.5 g per hectare.

[0237]

[0137] In some embodiments, provided methods comprise applying one or more ascarosides and thifluzamide. In some embodiments, thifluzamide is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application). In some embodiments, thifluzamide is applied at about 90 g per hectare.

[0238]

[0138] In some embodiments, provided methods comprise applying one or more ascarosides and a copper-containing fungicide. In some embodiments, a copper-containing fungicide is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application). In some embodiments, a copper-containing fungicide is applied at about 525 g per hectare.

[0239]

[0139] In some embodiments, provided methods comprise applying one or more ascarosides and copper hydroxide. In some embodiments, copper hydroxide is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower

[0240] 331652340 ASCB-018 / 01WO (360511-2180)amount / hectare, or less frequency of application). In some embodiments, copper hydroxide is applied at about 525 g per hectare.

[0241]

[0140] In some embodiments, provided methods comprise applying one or more ascarosides and Native™. In some embodiments, Native™ is applied at a lower than typical rate and / or amount (e.g., a lower concentration within a foliar spray, a lower amount / hectare, or less frequency of application). In some embodiments, Native™ is applied at about 150 g per hectare.

[0242]

[0141] In some embodiments, methods comprising applying one or more ascarosides in combination with other agrichemicals comprising applying the one or more ascarosides and the other agrichemicals within the same composition during the same application. In some embodiments, methods comprising applying one or more ascarosides in combination with other agrichemicals comprising applying the one or more ascarosides and the other agrichemicals within different compositions and applied at different times (e.g., either sequential or separated by an interval).

[0243]

[0142] In some embodiments, compositions or formulations comprising both the one or more ascarosides and the one or more agrichemicals can vary in composition and form. In some embodiments, compositions or formulations are in solid form and in some embodiments, such compositions or formulations are in liquid form. As referenced, in addition to the one or more ascarosides and the one or more agrichemicals, one or more inert ingredients, e.g., one or more agronomically acceptable carriers (also referred to as agriculturally acceptable or suitable adjuvants) are generally included within the formulation. It is preferred that non-toxic carriers be used in the formulations and methods of the present disclosure. The term “agronomically acceptable carrier” includes any carrier suitable for administration to a plant or soil, e.g., customary excipients in formulation techniques, such as used to form solutions (e.g., directly sprayable or dilutable solutions), emulsions, (e.g., emulsion concentrates and diluted emulsions), wettable powders, suspensions, soluble powders, powders, dusts, pastes, soluble powders, granules, suspension-emulsion concentrates, encapsulation into polymeric materials, coatable pastes, natural and synthetic materials impregnated with active compound and microencapsulations in polymeric substances. In some embodiments, agronomically acceptable carriers can include surfactants, emulsifiers, oils, salts, and the like.

[0244]

[0143] These compositions or formulations can be produced in a known manner, for example, by mixing the one or more ascarosides and the one or more agrichemicals with one or more agronomically acceptable carriers, such as liquid solvents or solid carriers, optionally with the

[0245] 331652340 ASCB-018 / 01WO (360511-2180)use of additional components including, but not limited to, surfactants, including emulsifiers, dispersants, foam-formers, colorants, processing aids, lubricants, fillers, reinforcements, flame retardants, light stabilizers, ultraviolet radiation absorbers, weather stabilizers, plasticizers, release agents, perfumes, heat-retaining additives (e.g., silica), cross-linking agents, antioxidants, anti-foaming agents, buffers, pH modifiers, compatibility agents, drift control additives, extenders / stickers, tackifiers, plant penetrants, safeners, spreaders, wetting agents, and the like. In some embodiments, such formulations can include one or more additional agrichemicals and / or one or more plant or plant product treatment compounds. Further, some compositions will be residual in that they do not easily wash off the leaves of a plant during rain and thus can protect against pests during and after rainy weather. The additional components noted herein can be added directly into the formulation as referenced above or alternatively can be added separately, e.g., at the time of application. In some embodiments, wetting agents, emulsifiers, spreaders, and the like are used in the formulations. Formulations include concentrated versions, in which the agrichemical is present in a concentration of from 0.001 to 98.0%, with the remaining content being agronomically acceptable carriers / adjuvants.

[0246]

[0144] In some embodiments, such compositions formulations, especially those with less than 50 percent of the one or more ascarosides, can be used directly, but these formulations may also be diluted with other agronomically acceptable carriers to form more dilute formulations for application. These latter formulations can include the one or more ascarosides in lesser concentrations of from 0.001 to 0.1 percent.

[0247]

[0145] In some embodiments, the compositions or 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. In some embodiments, the amount of adjuvant surfactant will typically vary from 0.01 to 1.0 percent by volume, based on a spray-volume of water, preferably 0.05 to 0.5 volume percent. Suitable adjuvant surfactants include, but are not limited to ethoxylated nonyl phenols, ethoxylated synthetic or natural alcohols, salts of the esters or sulfosuccinic 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- C16) ethoxylate; di -sec-butylphenol EO-PO block copolymer; poly siloxane -methyl cap;

[0248] 331652340 ASCB-018 / 01WO (360511-2180)nonylphenol ethoxylate + urea ammonium nitrate; emulsified methylated seed oil; tridecyl alcohol (synthetic) ethoxylate (8EO); tallow amine ethoxylate (15 EO); PEG(400) dioleate-99. In some embodiments, the compositions or formulations may also include oil-in-water emulsions. If the agronomically acceptable carrier is water, in some embodiments, an organic solvent may be incorporated as an auxiliary liquid solvent. Suitable liquid solvents include, for example, aromatics (e.g., xylene, toluene and alkylnaphthalenes); chlorinated aromatics or chlorinated aliphatic hydrocarbons (e.g., chlorobenzenes, chloroethylenes and methylene chloride); aliphatic hydrocarbons (e.g., cyclohexane); paraffins (e.g., petroleum fractions, mineral and vegetable oils); alcohols (e.g., butanol or glycol and their ethers and esters); ketones (e.g., acetone, methyl ethyl ketone, methyl isobutyl ketone and cyclohexanone) and strongly polar solvents (e.g., dimethylformamide and dimethyl sulfoxide). Other examples of organic solvents include, but are not limited to, 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 certain emulsifiable concentrates. 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.

[0249]

[0146] Suitable solid agronomically acceptable carriers include, for example, ammonium salts and ground natural minerals (e.g., kaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite and diatomaceous earth); ground synthetic minerals (e.g., highly disperse silica, alumina and silicates); crushed and fractionated natural rocks (e.g., calcite, marble, pumice, sepiolite and dolomite); synthetic granules of inorganic and organic meals; granules of organic material (e.g., sawdust, coconut shells, maize cobs and tobacco stalks). In some embodiments, dry compositions can comprise powders and the like.

[0250] 331652340 ASCB-018 / 01WO (360511-2180)

[0147] Suitable emulsifiers and foam-formers include, for example, nonionic and anionic emulsifiers (e.g., polyoxyethylene fatty acid esters, polyoxyethylene fatty alcohol ethers, for example, alkylaryl polyglycol ethers, alkylsulfonates, alkyl sulphates and arylsulfonates) protein hydrolysates.

[0251]

[0148] Suitable dispersants include, for example, lignin-sulfite waste liquors and methylcellulose. Tackifiers such as carboxymethylcellulose and natural and synthetic polymers in the form of powders, granules or lattices, such as gum arabic, polyvinyl alcohol and polyvinyl acetate, as well as natural phospholipids, such as cephalins and lecithins, and synthetic phospholipids, can be used in the disclosed compositions. 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, oil-soluble salts or sulfated polyglycolethers and appropriate salts of phosphated- polyglycol ether. Other additives may include, for example, mineral and vegetable oils.

[0252]

[0149] ‘ ‘Surfactants” (e.g., which can comprise typically about 0.5% to about 10% of a wettable powder) include sulfonated lignins, condensed naphthalene-sulfonates, the naphthalenesulfonates, alkyl-benenesulfonates, alkysulfonates or nonionic surfactants such as ethylene oxide adducts of alkylphenols or mixtures thereof

[0253]

[0150] Colorants such as inorganic pigments, for example, iron oxide, titanium oxide and Prussian Blue, and organic dyestuffs, such as alizarin dyestuffs, azo dyestuffs and metal phthalocyanine dyestuffs, and trace nutrients such as salts of iron, manganese, boron, copper, cobalt, molybdenum and zinc may also be included in the compositions.

[0254]

[0151] Methods of preparing solid and liquid compositions for agrichemical use are generally known and can be employed according to the present disclosure (where such methods involve incorporating one or more ascarosides and one or more agrichemicals) within such compositions). In some embodiments, compositions can be utilized as liquid concentrates, Ready-to-Use (RTU) liquid sprays, dusts, or solids, depending upon the needs of the user. Compositions according to the present disclosure can, in some embodiments, be in the form of granular material (including dusts, pellets, soluble powders, flowable powders, water-dispersible granules, and the like). In some embodiments, compositions according to the

[0255] 331652340 ASCB-018 / 01WO (360511-2180)present disclosure can be in liquid form (e.g., solutions, suspensions, or emulsions). In some embodiments, compositions are in the form of a granular material treated with a liquid comprising the one or more ascarosides and the one or more additional agrichemicals. In some embodiments, a composition comprising one or more ascarosides and one or more agrichemicals is formed into fibers or filaments and in some such embodiments, a woven or non-woven textile (e.g., film) can be produced therefrom. In some embodiments, a composition as provided herein is pelletized. In some embodiments, a composition as provided herein is in the form of a film, e.g., plastic mulch. Any of the solid compositions provided herein can optionally be coated via methods generally known in the art to delay release of the one or more ascarosides and the one or more agrichemicals. The formulation chosen will depend on the use of the product.

[0256]

[0152] 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.

[0257]

[0153] Wettable powders may be agglomerated or compacted to form water dispersible granules. These granules include mixtures of compound, inert carriers suitable for granular applications and surfactants. The concentration of the compound is typically between about 0.1% to about 90% 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.

[0258]

[0154] “Aqueous suspensions” may be prepared where the compounds are dispersed in an aqueous vehicle at a concentration typically in the range of between about 5% to about 50% by weight. The suspensions can be 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.

[0259]

[0155] The amount of the one or more ascarosides and the one or more agrichemicals included within such formulations can vary. In certain specific embodiments, the amount of the one or more ascarosides and the one or more agrichemicals is a synergistically effective amount.

[0260] 331652340 ASCB-018 / 01WO (360511-2180)Typically, the formulation will comprise a lower weight percentage of the one or more ascarosides than the one or more agrichemicals.

[0261]

[0156] In certain embodiments, provided combinations are characterized in that the amount of the one or more ascarosides represents a very low percentage of the composition or formulation. In certain embodiments, provided combinations are characterized in that ascarosides are present in an amount of less than 1 wt.% relative to the other active ingredient(s). In certain embodiments, provided combinations are characterized in that ascarosides are present in an amount of less than 0.1 wt% relative to the other active ingredient(s). In certain embodiments, provided combinations are characterized in that ascarosides are present in an amount of less than 0.05 wt.% relative to the other active ingredient(s). In certain embodiments, provided combinations are characterized in that ascarosides are present in an amount of less than 0.01 wt.% relative to the other active ingredient(s). In certain embodiments, provided combinations are characterized in that ascarosides are present less than 0.001 wt.% relative to the other active ingredient(s).

[0262] Examples

[0263] Example 1: Replicated small plot field trials to evaluate the effects of ascaroside treatment on symptoms of bacterial leaf blight (Xanthomonas oryzae) in rice.

[0264]

[0157] Field trials were conducted to mimic typical cultivation conditions for rice culture in Southern India where bacterial leaf blight is a frequent problem for growers.

[0265] Example la: Evaluation of effect of ascaroside application rate on bacterial leaf blight control in rice.

[0266]

[0158] At each selected site, a randomized small plot trial (6m x 4m plots with 4 replicates of each treatment) was planted and treated twice via foliar spray with a composition comprising the ascaroside ascr# 18 at rates of 12.5 mg, 25 mg, or 50 mg per hectare. The compositions were applied at a spray volume of 375 L per hectare corresponding to ascaroside concentrations of 0.033, 0.067, and 0.133 mg of per liter in the applied compositions. For comparison purposes, untreated control plots were included at each site. The severity of bacterial leaf blight (BLB) symptoms in each plot were measured at 15, 20, 25, 30, and 35 days after the second application. Figure 1, shows the average disease severity across the replicates for each treatment. Treatments with the ascaroside compositions resulted in a reduction of BLB symptoms, and a dose response was evident whereby the 25 mg and 50 mg / ha rates are more effective than the 12.5 mg rate.

[0267] 331652340 ASCB-018 / 01WO (360511-2180)Example lb: Evaluation of the efficacy of blends of ascarosides with commercial fungicides.

[0268]

[0159] To evaluate the ability of ascarosides to control bacterial leaf blight when applied in combination with commercial products, plots were treated with 25 mg of ascr# 18 alone or in a 2-way combination with commercial fungicide products including: Picoxystrobin 22.52 SC (applied at 150g Al / ha), Difenoconazole 25 EC (applied at 62.5g Al / ha), Thifluzamide 24 SC (applied at 90g Al / ha) Copper Hydroxide 53.8 DF (applied at 525g Al / ha) and Native™ 75 WG (a mixture of Tebuconazole and Trifloxystrobin, applied at 150g Al / ha) each applied at their recommended label rates for rice. For comparison purposes, untreated control plots and plots treated with each of the commercial fungicides without ascaroside were also included. As shown in Figure 2, addition of ascaroside improved the disease severity relative to the commercial fungicides alone.

[0269] Example 1c: Yield impact of ascaroside treatments

[0270]

[0160] Figure 3 shows the average yields for each treatment described in Examples la and lb. As shown in Figure 3, ascaroside treatment increases yield relative to untreated controls. The maximum yield increase for solo ascaroside treatments from Example la is observed at the 25 mg / ha rate, which increased yield by 1.8 metric tons per hectare relative to untreated. Each of the ascaroside combinations from Example lb also show improved yield relative to the solo fungicides.

[0271]

[0161] It is contemplated that compounds, compositions, and methods of the present application encompass variations and adaptations developed using information from the embodiments described in the present disclosure. Adaptation or modification of the methods and processes described in this specification may be performed by those of ordinary skill in the relevant art. It will be appreciated that use of headers in the present disclosure are provided for the convenience of the reader.

[0272]

[0162] The presence and / or placement of a header is not intended to limit the scope of the subject matter described herein. Unless otherwise specified, embodiments located in one section of the application apply throughout the application to other embodiments, both singly and in combination. Throughout the description, where compositions, compounds, or products are described as having, including, or comprising specific components, or where processes and methods are described as having, including, or comprising specific steps, it is contemplated that, additionally, there are articles, devices, and systems of the present application that consist

[0273] 331652340 ASCB-018 / 01WO (360511-2180)essentially of, or consist of, the recited components, and that there are processes and methods according to the present application that consist essentially of, or consist of, the recited processing steps. It should be understood that the order of steps or order for performing certain action is immaterial so long as the described method remains operable. Moreover, two or more steps or actions may be conducted simultaneously.

[0274]

[0163] All publications and patent applications mentioned in the specification are indicative of the level of those skilled in the art to which this invention pertains. All publications and patent applications are herein incorporated by reference to the same extent as if each individual publication or patent application was specifically and individually indicated to be incorporated by reference. Although the foregoing invention has been described in some detail by way of illustration and example for purposes of clarity of understanding, it will be obvious that certain changes and modifications may be practiced within the scope of the appended claims.

[0275] 331652340 ASCB-018 / 01WO (360511-2180)

Claims

CLAIMSWhat is claimed is:

1. A method for treating monocot plants exposed to bacterial pathogens, the method comprising applying one or more ascarosides to the plant.

2. A method for preventing or reducing damage to monocot plants by bacterial pathogens (e.g., a method for preventing or reducing Bacterial Leaf Blight, Bacterial Leaf Streak, Bacterial Sheath Blight, or Bacterial Rice Blast), the method comprising applying one or more ascarosides to the plant.

3. A method for increasing yields of monocot plants exposed to bacterial pathogens, the method comprising applying one or more ascarosides to the plant.

4. A method of controlling pathogens of the genus Xanthomonas in rice, the method comprising applying one or more ascarosides to the foliage of the plant.

5. The method of any one of claims 1-4, comprising applying an ascaroside composition comprising one or more ascarosides.

6. The method of any one of claims 1-5, wherein the application is performed by foliar spray.

7. The method of any one of claims 1-5, wherein the application is performed at least two times during the growing season.

8. The method of claim 7, wherein the interval between applications is at least 7d, at least 14d, at least 2 Id, or at least 28d.

9. The method of any one of claims 6-8, wherein the one or more ascarosides are present in the foliar spray at a concentration of 0.5 mg / L or less.

10. The method of any one of claims claim 6-9, wherein the one or more ascarosides are present in the foliar spray at a concentration less than 0.25 mg / L.

11. The method of any one of claims 6-9, wherein the one or more ascarosides are present in the foliar spray at a concentration less than 0.1 mg / L.

12. The method of any one of claims 6-9, wherein the one or more ascaroside are present in the foliar spray at a concentration between 0.01 and 0.15 mg of ascaroside per liter.

13. The method of any one of claims 1-12, wherein an ascaroside is a glycoside of a Cs-4o to-1 hydroxy fatty acid or an ester, amide, or salt thereof.

14. The method of claim 13, wherein the ascaroside is a glycoside of a Cs-12 co- 1 hydroxy fatty acid or an ester, amide, or salt thereof331652340 ASCB-018 / 01WO (360511-2180)15. The method of claim 14, wherein the ascaroside is selected from the group consisting of : ascr#9, ascr#12, ascr#14, ascrtfl, ascrtflO, ascr#16, ascr#18, ascr#20, ascr#22, ascr#24, ascr#26, ascr#28, ascr#30, ascr#32, ascr#34, and ascr#36; or is selected from the group consisting of: ascrtflO, ascr#16, ascr#18, ascr#20, ascr#22, and ascr#24; or is selected from the group consisting of: ascr#9, ascr#14, ascrtflO, and ascr#18; or wherein the ascaroside is ascr#18.

16. The method of any one of claims 1-12, wherein the ascaroside is a glycoside of a Cs-4o to-hydroxy fatty acid or an ester, amide, or salt thereof.

17. The method of claim 16, wherein the ascaroside is a glycoside of a Cs-12 to-hydroxy fatty acid or an ester, amide, or salt thereof.

18. The method of claim 17, wherein the ascaroside is selected from the group consisting of: ascr#5, oscr#9, oscr#12, oscrtfl, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36; or is selected from the group consisting of: oscrtflO, oscr#16, oscr#18, oscr#20, and oscr#22; or is selected from the group consisting of: bhas#5, oscr#9, oscr#12, oscr#l, oscr#14, oscr#10, oscr#16, oscr#18, oscr#20, oscr#22, oscr#24, oscr#26, oscr#28, oscr#30, oscr#32, oscr#34, and oscr#36; or is selected from the group consisting of: oscrtflO, oscr#16, oscr#18, oscr#20, and oscr#22; or wherein the ascaroside is oscr#1619. The method of any one of claims 1-18, wherein the monocot plant belongs to the genus Oryza.

20. The method of any one of claims 1-19, wherein the bacterial pathogen is a bacterium belonging to the genus Xanthomonas.

21. The method of any one of claims 1-20, wherein the bacterial pathogen comprises Xanthomonas oryzae.

22. The method of any one of claims 1-21, wherein the method comprises treating or preventing bacterial leaf blight.

23. The method of any one of claims 1-22, wherein the method comprises treating or preventing bacterial leaf streak.

24. The method of any one of claims 1-23, characterized in that the first treatment with ascaroside occurs between 0 and 2 weeks after transplant of the plant.

25. The method any one of claims 1-23, characterized in that the first treatment with ascaroside occurs between 2 and 4 weeks after transplant of the plant.331652340 ASCB-018 / 01WO (360511-2180)26. The method of any one of claims 1-25, wherein the ascaroside is applied at a rate of 100 mg per hectare or less.

27. The method of claim 26, wherein the ascaroside is applied at a rate of 50 mg per hectare or less.

28. The method of claim 27, wherein the ascaroside is applied at a rate of 25 mg per hectare or less.

29. The method of any one of claims 1-28, characterized in that damage from bacterial pathogens is reduced by at least 50% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

30. The method of claim 29, characterized in that the damage from pathogens, is reduced by at least 60%, at least 70% or at least 80% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

31. The method of any one of claims 1-30, characterized in that Bacterial Leaf Blight symptoms are reduced by at least 30%, at least 40%, at least 50%, least 60%, at least 70% or at least 80% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

32. The method of any one of claims 1-30, characterized in that Bacterial Leaf Streak symptoms are reduced by at least 30%, at least 40%, at least 50%, least 60%, at least 70% or at least 80% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

33. The method of any one of claims 1-30, characterized in that Bacterial Sheath Blight symptoms are reduced by at least 30%, at least 40%, at least 50%, least 60%, at least 70% or at least 80% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

34. The method of any one of claims 1-30, characterized in that Bacterial Rice Blast symptoms are reduced by at least 30%, at least 40%, at least 50%, least 60%, at least 70% or at least 80% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.

35. The method of any one of claims 1-34, characterized in that the yield is increased by at least 5% as compared to corresponding plants lacking application of the one or more ascarosides or ascaroside composition.331652340 ASCB-018 / 01WO (360511-2180)36. The method of claim 35, characterized in that the yield is increased by at least 10%, at least 15%, at least 20%, at least 25%, at least 30%, or at least 40% as compared to corresponding plants not treated with the one or more ascarosides or ascaroside composition.

37. The method of any one of claims 1-36, comprising application to a plot of monocot plants of at least 6m x 4m.

38. The method of any one of claims 1-36, comprising application to a plot of monocot plants of at least one acre.

39. The method of any one of claims 1-38, wherein the ascaroside is applied in combination with a fungicide.

40. The method of claim 39, characterized in that amount of fungicide administered is lower than the recommended rate on the label.

41. The method of claim 39 or 40, wherein the fungicide is picoxystrobin, difenoconazole, thifluzamide, a copper-containing fungicide (e.g., copper hydroxide), or Native™42. The method of claim 41, wherein the fungicide is picoxystrobin.

43. The method of claim 41 or 42, wherein picoxystrobin is applied at a rate of about 150 g per hectare.

44. The method of claim 41, wherein the fungicide is difenoconazole.

45. The method of claim 41 or 44, wherein difenoconazole is applied at a rate of about 63.5 g per hectare.

46. The method of claim 41, wherein the fungicide is thifluzamide.

47. The method of claim 41 or 46, wherein thifluzamide is applied at a rate of about 90 g per hectare.

48. The method of claim 41, wherein the fungicide is a copper-containing fungicide.

49. The method of claim 41 or 48, wherein the fungicide is copper hydroxide.

50. The method of claim 41, 48, or 49, wherein copper hydroxide applied at a rate of about 525 g per hectare.

51. The method of claim 41 , wherein the fungicide is Nativo™.

52. The method of claim 41 or 51, wherein Nativo™ applied at a rate of about 90 g per hectare.331652340 ASCB-018 / 01WO (360511-2180)

Images