Oxazoline sugar compound and its preparation method and use

Abstract

The present invention provides a zolinose compound represented by formula (I), its preparation method, and use, wherein the substituents are defined as described in the specification. These zolinose compounds have promising applications in asymmetric synthesis of complex molecules, site-selective modification of sugar rings, flexible assembly of oligosaccharides and glycopeptides, and specific glycosylation modification of peptides and proteins. They provide a synthetic toolkit based on novel "zolinoses" for medicinal chemistry or chemical biology research. #imgabs0#

Description

Technical Field

[0001] The present invention relates to the fields of organic chemistry, medicinal chemistry, bioanalysis, chemical biology and pharmacotherapy, and in particular to zolinose compounds and pharmaceutical compositions thereof, preparation methods and uses thereof as synthetic intermediates. Background Art

[0002] Sugars and glycosides are widely present in glycoproteins and glycopeptides, natural products, and drug molecules, as shown in the following formulas.

[0003]

[0004] Chemical synthesis of sugars is an important approach to obtaining carbohydrate compounds for studying their physiological functions. Chemical modification of sugars can also yield characteristic glycopeptides for studying the functions of glycoproteins. Sugar rings in natural products and drug molecules can be modified to obtain analogs for the development of new drugs.

[0005] Current methods for synthesizing sugars (glycosides) and chemically modifying sugar rings primarily rely on complex, multi-step, and inefficient selective hydroxyl protection processes. A simple, efficient synthetic method that can flexibly modify sugar rings at multiple sites while simultaneously yielding substrates amenable to glycosylation reactions is lacking.

[0006] Oligopeptides and polypeptides not only exist in the human body and play key physiological roles, but many peptide drugs have also been widely used in clinical practice to maintain human health. Although peptides are highly active, they are easily degraded, have a short half-life in the body, and are easily destroyed by oral administration. Therefore, chemical modification of peptides is an important approach to improve their in vivo stability and enable oral administration.

[0007] Proteins are important targets for drug research. Exploring the relationship between protein structure and function is fundamental to drug design, and protein chemical modification methods are a common approach to studying this relationship. However, current methods for protein chemical modification still have significant limitations, with the lack of specific chemical modification reagents being a major issue. Therefore, developing chemical modification reagents and methods that can selectively modify specific amino acid residues in proteins under physiological conditions could be applied to drug discovery and design research, as well as chemical biology studies.

[0008] While conducting research on the structural optimization, design, and synthesis of berberine, an active ingredient in traditional Chinese medicine (Eur. J. Med. Chem., 2013, 70, 677-684), Li Bo et al. stumbled upon a novel acetal rearrangement reaction (Eur. J. Med. Chem., 2014, 77, 204-210). Inspired by this discovery, they developed a method for constructing 4-methoxyoxazoline compounds by cyclizing a cyano compound with a glycolaldehyde dimethyl acetal in the presence of an acid (Synthesis 2016, 48, 1331-1343). Based on this, the inventors of the present application further developed the following invention. Summary of the Invention

[0009] The present invention develops a novel oxazoline sugar compound, wherein the oxazoline unsaturated sugar compound can be conveniently converted into an α,β unsaturated ketone and can directly undergo a selective halogenation reaction with a halogenating agent, thereby achieving selective modification of the 2-, 3-, and 4-positions of the sugar ring; the oxazoline saturated sugar compound can be simply converted into a 1-amino sugar compound with selective ester protection at the 2-position, which is used to construct an N-glycoside with a 1,2-position cis-glycosidic bond; selective modification of the 3-position of the sugar ring can also be simply achieved, and a 1-amino sugar building block with selective modification of the 2,3-positions can be further obtained; in addition, the amino group at the 1-position of the sugar ring can be conveniently converted into a hydroxyl group, thereby achieving the conversion from 1-amino sugar to 1-hydroxy sugar; and, since the oxazoline sugar compound itself carries an excellent oxazoline chiral group, it can also be directly used in asymmetric synthesis to construct complex chiral molecules.

[0010] Through further research, the inventors of the present application discovered that the aforementioned oxazoline unsaturated carbohydrate compounds can undergo specific coupling reactions with the sulfhydryl groups of cysteine ​​residues in peptide molecules under physiological conditions. Other sensitive groups such as primary amine amino groups, secondary amine amino groups, amide amino groups, alcohol hydroxyl groups, phenolic hydroxyl groups, disulfide bonds, carboxyl groups, etc. do not affect the coupling reaction, and thus can be used for specific glycosylation modification of peptides or proteins.

[0011] In summary, this application provides novel oxazoline sugar compounds and their preparation methods, and develops a set of synthetic methods that can apply this type of oxazoline sugar to the asymmetric synthesis of complex molecules, site-selective modification of sugar rings, mobile assembly of oligosaccharides and glycopeptides, and specific glycosylation modification of peptides or proteins, providing a synthetic toolkit based on the novel "oxazoline sugar" for the research of medicinal chemistry or chemical biology.

[0012] An object of the present invention is to provide an oxazoline carbohydrate compound represented by formula I or a pharmaceutically acceptable salt thereof.

[0013] Another object of the present invention is to provide a method for preparing the oxazoline sugar compound of formula I.

[0014] Another object of the present invention is to provide the use of the oxazoline sugar compound of formula I as a synthetic intermediate.

[0015] Another object of the present invention is to provide compounds of formula IV, formula V, and formula VI or pharmaceutically acceptable salts thereof prepared from the compound of formula I.

[0016] According to one aspect of the present invention, there is provided an oxazoline carbohydrate compound represented by formula I or a pharmaceutically acceptable salt thereof:

[0017]

[0018] in, is a double bond or a single bond;

[0019] n is 0 or 1, especially 1;

[0020] R 1 is 1 or 2 substituents on ring A, selected from C1-C6 alkyl which is unsubstituted or substituted with hydroxy, C1-C6 alkanoyloxy, C6-C12 aroyloxy or C6-C12 aryloxy, C1-C6 alkanoyloxy which is unsubstituted or substituted with C1-C6 alkyl, C1-C6 alkoxy which is unsubstituted or substituted with C6-C12 aryl, C6-C12 aryloxy which is unsubstituted or substituted with C1-C6 alkyl, C6-C12 aryloxy which is unsubstituted or substituted with C1-C6 alkyl, hydroxy, monosaccharidyloxy, disaccharidyloxy, oligosaccharidyloxy, polysaccharidyloxy, hydrogen; preferably, R 1 R is one or two substituents on the A ring selected from C1-C3 alkyl which is unsubstituted or substituted with hydroxy, C1-C6 alkanoyloxy, C6-C12 aroyloxy or C6-C12 aryloxy (particularly C1-C3 alkyl which is unsubstituted or substituted with hydroxy, C1-C3 alkanoyloxy or C6-C12 aryloxy), C1-C3 alkanoyloxy which is unsubstituted or substituted with C1-C3 alkyl, C1-C3 alkoxy which is unsubstituted or substituted with C6-C12 aryl, C6-C12 aryloxy which is unsubstituted or substituted with C1-C3 alkyl, C6-C12 aryloxy which is unsubstituted or substituted with C1-C3 alkyl, hydroxy, monosaccharidyloxy, disaccharidyloxy, hydrogen; more preferably, R 1 is one or two substituents on ring A selected from C1-C3 alkyl, benzyloxy C1-C3 alkyl, hydroxy C1-C3 alkyl, C1-C6 alkanoyloxy C1-C3 alkyl (especially C1-C3 alkanoyloxy C1-C3 alkyl), C6-C12 aroyloxy C1-C3 alkyl, C1-C3 alkyl C1-C3 alkanoyloxy, C1-C3 alkanoyloxy, C1-C3 alkoxy, C6-C12 aryloxy, C6-C12 arylformyloxy, hydroxy, monosaccharidyloxy, disaccharidyloxy, benzyloxy, and hydrogen;

[0021] R 2is selected from C1-C6 alkyl, C3-C6 cycloalkyl, substituted or unsubstituted C6-C12 aryl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the C6-C12 aryl are 1, 2, 3 or 4 substituents selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C6 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, phenyl, or two adjacent substituents on the C6-C12 aryl together with the connected aryl carbon atom constitute a 5-9 membered heterocyclic group, and the substituents of the 5-9 membered heteroaryl are Halogen; preferably, selected from C1-C6 alkyl, C3-C6 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the phenyl group are 1, 2, 3 or 4 substituents selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C3 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, phenyl, or two adjacent substituents on the phenyl group together with the connected phenyl carbon atom constitute a 5-9 membered heterocyclic group, and the substituent of the 5-9 membered heteroaryl group is halogen; more preferably, R 2 selected from C1-C3 alkyl, C3-C5 cycloalkyl, naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the phenyl group are 1, 2, 3 or 4 substituents selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, trifluoromethyl, C1-C3 alkanoyl, C2-C4 alkynyl, and phenyl, or two adjacent substituents on the phenyl group together with the connected phenyl carbon atom form a dioxolane, and the substituents of the 5-9 membered heteroaryl group are selected from F, Cl, Br, and I;

[0022] R 3 is selected from hydrogen, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy, hydroxy, monosaccharidyloxy, disaccharidyloxy, oligosaccharidyloxy, polysaccharidyloxy; preferably, hydrogen, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy (especially C1-C3 alkoxy), C6-C12 aryloxy; more preferably, R 3 Selected from hydrogen, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C6 alkoxy (especially C1-C3 alkoxy), C6-C12 aryloxy;

[0023] R 4is selected from hydrogen, hydroxy, C1-C6 alkanoyloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C6 alkoxy; preferably, hydrogen, hydroxy, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C3 alkyl substituted or unsubstituted C6-C12 aryloxy, C1-C3 alkoxy; preferably, R 4 Selected from hydrogen, hydroxy, C1-C6 alkanoyloxy (especially C1-C3 alkanoyloxy), C1-C3 alkoxy, C6-C12 aryloxy;

[0024] Q is O, N or S, especially O;

[0025] W is O, N or S, especially O.

[0026] In particular, R 1 is one or two substituents on ring A selected from acetoxymethyl, valeryloxymethyl, benzoyloxymethyl, benzyloxymethyl, acetoxy, valeryloxy, benzoyloxy, methyl, ethyl, hydroxyl, hydroxymethyl, monosaccharidyloxy, disaccharidyloxy, benzyloxy and hydrogen.

[0027] In particular, R 2 is selected from methyl, ethyl, naphthyl, substituted or unsubstituted phenyl, and substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the phenyl group are 1, 2, 3 or 4 substituents selected from methyl, ethyl, methoxy, ethoxy, F, Cl, Br, I, trifluoromethyl, acetyl, ethynyl, and phenyl; or, two adjacent substituents on the phenyl group together with the connected phenyl carbon atom form a dioxolane ring; the 5-9 membered heteroaryl group is selected from thienyl and furyl, and its substituents are selected from F, Cl, Br, and I.

[0028] In particular, R 3 is selected from hydrogen, acetyloxy, valeryloxy, benzoyloxy and benzyloxy.

[0029] In particular, R 4 is selected from hydrogen, hydroxy, acetoxy, valeryloxy, benzoyloxy and benzyloxy.

[0030] In particular, the compound of formula I above may be a compound of formula II or formula III below

[0031]

[0032] Among them, n, R 1 , R 2 , R 3 , R 4 , W and Q are defined as above.

[0033] In this article,

[0034] C1-C6 alkyl refers to a straight-chain or branched saturated alkyl group having 1 to 6 carbon atoms, such as methyl, ethyl, propyl, and tert-butyl.

[0035] The C2-C6 alkynyl group refers to an alkynyl group having 2 to 6 carbon atoms and a carbon-carbon triple bond, for example, ethynyl and 2-propynyl.

[0036] C1-C6 alkanoyloxy refers to RC(=O)O-, wherein R is a C1-C6 alkyl group as defined above, for example, formyloxy or acetoxy.

[0037] C1-C6 alkanoyl refers to RC(=O)-, wherein R is a C1-C6 alkyl group as defined above, for example, acetyl or propionyl.

[0038] C6-C12 aryl refers to a monocyclic aromatic group or a condensed or non-condensed polycyclic aromatic group having 6 to 14 carbon atoms. In the case of a polycyclic carbon ring, as long as one carbon ring is an aromatic ring, for example, phenyl, benzyl, and naphthyl.

[0039] C6-C12 aryloxy refers to RO-, wherein R is a C6-C12 aryl group, for example, phenoxy or benzyloxy.

[0040] C1-C6 alkoxy refers to RO-, wherein R is a C1-C6 alkyl group as defined above, for example, methoxy, ethoxy, or propoxy.

[0041] C6-C12 aryloxy refers to RC(=O)O-, wherein R is a C6-C12 aryl group as defined above, for example, benzoyloxy.

[0042] C6-C12 aromatic acyl refers to RC(=O)-, wherein R is a C6-C12 aromatic group, as defined above, for example, benzoyl or phenylacetyl.

[0043] Monosaccharide radical refers to RO-, wherein R is a monosaccharide radical, and the monosaccharide radical refers to a sugar containing 3 to 6 carbon atoms in the molecular structure, such as glyceraldehyde of the trisaccharide; erythrose and threose of the tetrasaccharides; arabinose, ribose, xylose, and lyxose of the pentoses; and glucose, mannose, fructose, and galactose of the hexoses.

[0044] Disaccharidyloxy refers to RO—, wherein R is a disaccharidyl group, and the disaccharidyl group may be, for example, maltose, lactose, sucrose, trehalose, or gentiobiose.

[0045] Oligosaccharidyloxy refers to RO-, wherein R is an oligosaccharidyl group, and the oligosaccharidyl group may be, for example, maltooligosaccharide, cyclodextrin, fructooligosaccharide, or soybean oligosaccharide.

[0046] Polysaccharide-based oxy groups refer to RO-, wherein R is a polysaccharide group, such as starch, cellulose, glycogen, and inulin.

[0047] C3-C6 cycloalkyl refers to a saturated monocyclic hydrocarbon group having 3 to 8 carbon atoms, for example, cyclopropyl, cyclobutyl, and cyclopentyl.

[0048] The 5-9 membered heterocyclic group refers to a non-aromatic ring group having 5-9 ring atoms and 1-4 heteroatoms in the ring, wherein the heteroatom refers to nitrogen, oxygen or sulfur, for example, azetidinyl, pyrrolidinyl, pyrrolinyl, tetrahydrofuranyl, dihydrofuranyl, piperazinyl, piperidinyl, morpholinyl and dioxolane.

[0049] 5-9 membered heteroaryl refers to a monocyclic or polycyclic aromatic ring group having 5-9 ring atoms, which contains 1-4 heteroatoms in the ring, where the heteroatom refers to nitrogen, oxygen or sulfur, for example, pyrrolyl, pyrazolyl, imidazolyl, oxazolyl, pyridinyl, pyrimidinyl, furanyl, thienyl, isoxazolyl and indolyl.

[0050] Halogen refers to F, Cl, Br, and I.

[0051] The halo-substituted C1-C6 alkyl group refers to a C1-C6 alkyl group substituted with halogen, for example, trifluoromethyl, trichloromethyl, difluoromethyl, and difluoromethylene.

[0052] Herein, the substituent expression "A group B group" means that the B group is a group connected to the parent core, which is substituted by the A group. For example, C1-C3 alkanoyloxy C1-C3 alkyl means that the C1-C3 alkyl group connected to the parent core is substituted by a C1-C3 alkanoyloxy group; for example, acetoxymethyl means that the methyl group connected to the parent core is substituted by an acetoxy group.

[0053] Specifically, the compound of formula I is shown below:

[0054]

[0055]

[0056]

[0057]

[0058]

[0059] According to another aspect of the present invention, a method for preparing an oxazoline sugar compound as shown in formula I is provided: Compound 1 and Compound 2 are reacted in solvent S under the action of A to generate a compound as shown in formula I

[0060]

[0061] Specifically, the method includes the following methods shown in Route 2 and Route 3:

[0062]

[0063] Among them, n, R 1 , R 2 , R 3 , R 4 , W and Q are defined as above, R 5 and R 6 is selected from substituted or unsubstituted C1-C6 alkanoyl, substituted or unsubstituted C6-C12 aroyl, substituted or unsubstituted C6-C12 aryl or C1-C6 alkyl, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; U is defined the same as W.

[0064] As shown in route 2, compound 1 and compound 2 are reacted in solvent S1 in the presence of A1 to generate compound II;

[0065] As shown in Scheme 3, compound 1 and compound 2 are reacted in solvent S2 in the presence of A2 to generate compound III;

[0066] wherein A, A1 and A2 are Lewis acids, protic acids or a combination of Lewis acids and protic acids;

[0067] wherein S, S1 and S2 are aprotic solvents, protic solvents or a combination of aprotic solvents and protic solvents;

[0068] The Lewis acid is preferably selected from one or more of metal halides, such as ferric chloride, zinc dichloride, aluminum chloride, ruthenium trichloride, niobium pentachloride, antimony pentafluoride, and trifluoromethanesulfonates, such as silver trifluoromethanesulfonate, indium trifluoromethanesulfonate, lanthanum trifluoromethanesulfonate, ytterbium trifluoromethanesulfonate, and copper trifluoromethanesulfonate;

[0069] The proton acid is preferably one or more selected from common proton acids such as hydrochloric acid, sulfuric acid, acetic acid, trifluoroacetic acid, methanesulfonic acid, trifluoromethanesulfonic acid, etc.;

[0070] Preferably, A1 is a protonic acid, more preferably trifluoromethanesulfonic acid;

[0071] A2 is a protonic acid, more preferably trifluoromethanesulfonic acid.

[0072] The aprotic solvent includes but is not limited to toluene, acetone, dichloromethane, 1,2-dichloroethane, tetrahydrofuran, acetonitrile, xylene, chlorobenzene, dioxane, dimethyl sulfoxide, dimethylformamide, and dimethylacetamide;

[0073] The protic solvent includes but is not limited to n-butanol, n-propanol, ethanol, methanol, glycerol, ethylene glycol, and water;

[0074] Preferably, S1 is a combination of dichloromethane and water or a combination of dichloroethane and water;

[0075] S2 is dichloromethane or dichloroethane.

[0076] According to another aspect of the present invention, provided are uses of oxazoline carbohydrate compounds (compounds of Formula II and Formula III) as shown in Formula I for specific modification of different sites on the sugar ring (Routes 4 and 5), for the mobile assembly of oligosaccharides and glycopeptides (Route 4), and for the detection of sulfhydryl-containing molecules and the specific modification of sulfhydryl groups in peptides and proteins (Route 6).

[0077] According to the use of the present invention as described above, the use includes a method for synthesizing the following compounds of formula IV, formula V and formula VI from the oxazoline sugar compounds (compounds of formula II and formula III) as shown in formula I, and the method includes the following routes 4, 5 and 6:

[0078]

[0079] Compound II reacts with an acid to generate compound IV in which R8 is hydrogen, and then reacts with a carboxylic acid, an acid anhydride, an acid chloride, a boronic acid compound, or a halogenated compound to convert it into compound IV in which R8 is not hydrogen;

[0080] Among them, n, R 1 , R 2 , R 3 , W and Q are defined as above, R 8 It is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, 2-(tert-butoxycarbonylamino) methyl pentanoate-4-carbonyl, and p-methylphenylboronic acid.

[0081] In the method for synthesizing the compound of formula IV, the acid includes but is not limited to a protonic acid, a Lewis acid, or a combination thereof, wherein the protonic acid and the Lewis acid are as defined above;

[0082]

[0083] When X is hydrogen, compound V can be obtained by reacting compound III with water in the presence of an acid (Route 5);

[0084] When X is a halogen, compound V can be obtained by reacting compound III with a halogenating agent (Route 5);

[0085] Among them, R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , W and Q are as defined above, and X is hydrogen or halogen.

[0086] In the synthesis method of the compound of formula V, the halogenating agent includes but is not limited to N-bromosuccinimide, iodine monochloride, etc.;

[0087] Another aspect of the present invention provides a method for synthesizing the compound of formula VI, which comprises, as shown in Scheme VI,

[0088]

[0089] Compound III reacts with a thiol compound to convert into compound VI;

[0090] Among them, R 1 , R 2 , R 4 , W and Q are defined as above, R 7 Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, oligopeptide or polypeptide or protein containing cysteine ​​residue, wherein the substituent for substitution is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy.

[0091] In the synthesis method of the compound of formula VI, the thiol-containing compound includes but is not limited to thiol, cysteine, and oligopeptides, polypeptides and proteins containing cysteine ​​structures.

[0092] According to another aspect of the present invention, there is provided the following compound prepared from the compound of formula I:

[0093]

[0094] Among them, n, R 1 , R 2 , R 3 , W and Q are defined as above; R 7 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, oligopeptide or polypeptide or protein containing cysteine ​​residue, wherein the substituent for substitution is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; R 8 is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, 2-(tert-butoxycarbonylamino)pentanoic acid methyl ester-4-carbonyl, and X is hydrogen or halogen.

[0095] In particular, the compound prepared from the compound of formula I is selected from:

[0096]

[0097]

[0098]

[0099] Beneficial effects

[0100] The present invention designs and synthesizes oxazoline sugar compounds, which have novel structures and can be used as drug synthesis intermediates to achieve asymmetric synthesis of complex molecules. They can achieve specific modification of different sites on the sugar ring and flexible assembly of oligosaccharides and glycopeptides. They can also be used for the detection of sulfhydryl-containing molecules and the specific modification of sulfhydryl groups in peptides or proteins, and have great scientific value and potential economic benefits. BRIEF DESCRIPTION OF THE DRAWINGS

[0101] Figure 1 X-ray single crystal diffraction pattern of II-4'

[0102] Figure 2 X-ray single crystal diffraction pattern of III-1

[0103] Figure 3 is the mass spectrum of compound VI-2;

[0104] Figure 4 is the mass spectrum of compound VI-3. DETAILED DESCRIPTION

[0105] The present invention will be further described below with reference to specific embodiments, but the present invention is not limited thereto.

[0106] The preparation example of the oxazoline sugar of formula I of the present invention is as follows:

[0107]

[0108] The following is an example of the preparation of the compound of formula II:

[0109] Example II-1 Preparation of Compound II-1

[0110]

[0111] β-D-glucose pentaacetate (195 mg, 0.5 mmol) was weighed and dissolved in dichloromethane (10 ml). Benzonitrile (50 μl, 0.6 mmol) and water (11 μl, 0.6 mmol) were added and stirred thoroughly. Trifluoromethanesulfonic acid (106 μl, 1.2 mmol) was slowly added to the reaction mixture and allowed to react for 2 hours. After completion, deionized water (20 ml) was added to quench the reaction and the mixture was extracted twice with ethyl acetate (15 ml). The organic phases were then combined, washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was evaporated to dryness under reduced pressure on a rotary evaporator and redissolved in dichloromethane. The sample was mixed with silica gel and separated by silica gel column chromatography using a PE:EA ratio of 2:1 to afford 144.3 mg of the product as a yellow oil in a 74% yield. 1 H NMR (500MHz, CDCl3) δ8.05(m,2H),7.64–7.54(m,1H),7.48(m,2H),6.12(d,J=7.7Hz,1H),5.33(t,J=4.1Hz,1H),5.0 6–4.98(m,1H),4.66(m,1H),4.34(dd,J=12.1,5.1Hz,1H),4.28–4.17(m,2H),2.18(s,3H),2.12(s,3H),1.97(s,3H). 13 C NMR (125MHz, CDCl3) δ170.68,169.53,169.47,166.59,132.68,128.90,128.59,12 6.22,93.24,75.83,70.56,68.08,67.30,63.28,20.88,20.79,20.62.HRMS(ESI):C 19 H 22 NO8[M+H] + Calculated value: 392.134, measured value: 392.1351.

[0112] Example II-2 Preparation of Compound II-2

[0113]

[0114] p-Anisonitrile (66.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 123.1 mg of yellow oily product with a yield of 57%. 1H NMR (600MHz, CDCl3) δ7.96(d,J=8.6Hz,2H),6.94(d,J=8.6Hz,2H),6.05(d,J=7.6Hz,1H),5.29(dd,J=5.2,2.9Hz,1H),5.02–4 .94(m,1H),4.65–4.56(m,1H),4.30(dd,J=12.2,5.0Hz,1H),4.17(m,2H),3.85(s,3H),2.15(s,3H),2.08(s,3H),1.94(s,3H). 13 C NMR (150MHz, CDCl3) δ170.59,169.45,169.38,166.30,163.05,130.68,113.85,93.11,75.6 1,70.49,67.78,67.23,63.18,55.36,20.79,20.70,20.55.HRMS (ESI): C 20 H 24 NO9[M+H] + Calculated value: 422.1446, measured value: 422.1449.

[0115] Example II-3 Preparation of Compound II-3

[0116]

[0117] m-Anisonitrile (66.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 123.1 mg of yellow oily product with a yield of 57%. 1 H NMR (600MHz, CDCl3) δ7.60(m,1H),7.55(m,1H),7.36(m,1H),7.10(m,1H),6.08(d,J=7.7Hz,1H),5.30(d,J=4.1Hz,1H),4.98(m ,1H),4.63(m,1H),4.31(m,1H),4.19(dd,J=12.1,2.9Hz,1H),3.85(s,3H),3.75(m,1H),2.15(s,3H),2.09(s,3H),1.95(s,3H). 13C NMR (150MHz, CDCl3) δ170.57,169.44,169.35,166.46,159.51,129.56,121.20,119.35,11 3.05,93.07,75.70,70.33,67.93,67.16,63.16,55.40,20.78,20.69,20.54.HRMS (ESI): C 20 H 24 NO9[M+H] + Calculated value: 422.1446, measured value: 422.1449.

[0118] Example II-4 Preparation of Compound II-4

[0119]

[0120] Piperonitrile (73.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 135.5 mg of yellow oily product with a yield of 62%. 1 H NMR(600MHz, CDCl3)δ7.59(m,1H),7.46(s,1H),6.86(m,1H),6.08–6.01(m,3H),5.28(m,1H),5.00–4.93(m ,1H),4.60(m,1H),4.31(dd,J=12.2,5.0Hz,1H),4.22–4.15(m,2H),2.15(s,3H),2.09(s,3H),1.97(s,3H). 13 CNMR (150MHz, CDCl3) δ170.23,169.13,169.08,165.67,150.98,147.41,123.89,119.52,108.3 4,107.83,101.35,92.72,75.43,70.15,67.49,66.81,62.78,20.33,20.31,20.20.HRMS (ESI): C 20 H 22 NO 10 [M+H] + Calculated value: 436.1238, measured value: 436.1248.

[0121] Compound II-4 was treated with triethylamine / methanol to remove the acetyl protecting group to obtain solid compound II-4', and its structure was determined by X-ray single crystal diffraction experiment ( Figure 1 )as follows:

[0122]

[0123] Example II-5 Preparation of Compound II-5

[0124]

[0125] 4-Chlorobenzonitrile (68.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 57.5 mg of yellow oily product with a yield of 27%. 1 H NMR (600MHz, CDCl3) δ7.95(d,J=8.6Hz,2H),7.46–7.39(m,2H),6.07(d,J=7.7Hz,1H),5.30–5.24(m,1H),4.97(m,1H),4.63( m,1H),4.30(dd,J=12.1,5.1Hz,1H),4.18(dd,J=12.1,2.9Hz,1H),3.76–3.67(m,1H),2.15(s,3H),2.08(s,3H),1.94(s,3H). 13 C NMR (150MHz, CDCl3) δ170.54,169.36,165.53,138.98,130.09,128.86,124.56 ,93.15,75.97,70.44,68.11,67.05,63.08,20.76,20.68,20.52.HRMS(ESI):C 19 H 21 ClNO8[M+H] + Calculated value: 426.0950, measured value: 426.0955.

[0126] Example II-6 Preparation of Compound II-6

[0127]

[0128] 4-Bromobenzonitrile (90 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 51.7 mg of yellow oily product with a yield of 22%. 1H NMR (600MHz, CDCl3) δ7.88(d,J=8.5Hz,2H),7.60(d,J=8.3Hz,2H),6.07(d,J=7.7Hz,1H),5.28(dd,J=9.7,5.4Hz,1H),5.01–4.95(m ,1H),4.63(m,1H),4.30(dd,J=12.1,5.1Hz,1H),4.18(dd,J=12.1,2.8Hz,1H),3.73(m,1H),2.16(s,3H),2.09(s,3H),1.95(s,3H). 13 C NMR (150MHz, CDCl3) δ170.55,169.37,165.65,131.85,130.23,127.56,125.01 ,93.15,75.97,70.43,68.12,67.05,63.08,20.76,20.68,20.53.HRMS(ESI):C 19 H 21 BrNO8[M+H] + Calculated value: 470.0445, measured value: 470.0442.

[0129] Example II-7 Preparation of Compound II-7

[0130]

[0131] 4-Trifluoromethylbenzonitrile (85.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 48.3 mg of yellow oily product with a yield of 21%. 1 H NMR (600MHz, CDCl3) δ8.20–8.13(m,2H),7.75(d,J=8.1Hz,2H),6.14(d,J=7.8Hz,1H),5.32(m,1H),5.01(m,1H),4.70(m,1 H),4.33(dd,J=12.1,5.1Hz,1H),4.21(dd,J=12.2,2.9Hz,1H),3.79–3.72(m,1H),2.19(s,3H),2.11(s,3H),1.98(s,3H). 13C NMR (150MHz, CDCl3) δ170.67,169.50,169.48,165.27,129.30,125.64,125.61 ,93.25,76.25,70.51,68.34,67.11,63.14,20.88,20.80,20.64.HRMS(ESI):C 20 H 21 F3NO8[M+H] + Calculated value: 460.1214, measured value: 460.1212.

[0132] Example II-8 Preparation of Compound II-8

[0133]

[0134] Acetylbenzonitrile (72.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 79.6 mg of yellow oily product with a yield of 35%. 1 H NMR (600MHz, CDCl3) δ8.14–8.08(m,2H),8.02(d,J=8.7Hz,2H),6.11(d,J=7.8Hz,1H),5.32–5.26(m,1H),4.98(m,1H),4.66(m,1 H),4.31(dd,J=12.2,5.1Hz,1H),4.19(dd,J=12.1,2.9Hz,1H),3.74(m,1H),2.64(s,3H),2.16(s,3H),2.08(s,3H),1.94(s,3H). 13 C NMR (150MHz, CDCl3) δ197.20,170.54,169.36,165.48,139.90,130.03,129.03,128.30,12 8.27,93.18,76.03,70.40,68.27,67.00,63.06,26.73,20.76,20.68,20.52.HRMS (ESI): C 21 H 24 NO9[M+H] + Calculated value: 434.1446, measured value: 434.1453.

[0135] Example II-9 Preparation of Compound II-9

[0136]

[0137] 3,4,5-Methoxybenzonitrile (96.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 161.9 mg of a transparent oily product with a yield of 67%. 1 H NMR (500MHz, CDCl3) δ7.27 (s, 2H), 6.07 (d, J = 7.6Hz, 1H), 5.34–5.29 (m, 1H), 4.99 (m, 1H), 4.62 (m, 1H), 4.32 (dd,J=12.1,4.9Hz,1H),4.19(dd,J=12.1,2.9Hz,1H),3.91(d,J=2.0Hz,9H),3.79–3.71(m,1H),2.16(s,3H),2.09(s,3H),1.97(s,3H). 13 C NMR (125MHz, CDCl3) δ170.23,169.06,165.99,152.72,141.51,120.69,105.64,92.71,75 .60,70.05,67.43,66.89,62.75,60.54,55.90,29.25,20.45,20.36,20.23.HRMS (ESI): C 22 H 28 NO 11 [M+H] + Calculated value: 482.1657, measured value: 482.1662.

[0138] Example II-10 Preparation of Compound II-10

[0139]

[0140] 4-2-Cyanofuran (46.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 131.5 mg of yellow oily product with a yield of 69%. 1H NMR (600MHz, CDCl3) δ7.61 (dd, J=1.8, 0.8Hz, 1H), 7.12 (dd, J=3.5, 0.8Hz, 1H), 6.54 (dd,J=3.5,1.7Hz,1H),6.06(d,J=7.6Hz,1H),5.27–5.23(m,1H),4.98–4.95(m,1H) ,4.59(ddd,J=7.7,3.7,0.9Hz,1H),4.29(dd,J=12.1,5.1Hz,1H),4.16(dd,J=9.7,2 .5Hz,1H),3.75(ddd,J=8.2,5.1,2.8Hz,1H),2.13(s,3H),2.07(s,3H),1.96(s,3H). 13 C NMR (150MHz, CDCl3) δ170.55,169.40,169.28,158.24,146.55,146.48,146.35,141.42,11 6.92,111.90,92.96,75.69,70.40,67.93,67.04,63.00,20.73,20.66,20.51.HRMS (ESI): C 17 H 20 NO9[M+H] + Calculated value: 382.1133, measured value: 382.1143.

[0141] Example II-11 Preparation of Compound II-11

[0142]

[0143] 3-Cyanothiophene (54 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 106.7 mg of yellow oily product with a yield of 56%. 1 H NMR (600MHz, CDCl3) δ8.05(dd,J=3.0,1.2Hz,1H),7.58(dd,J=5.1,1.2Hz,1H),7.38(dd,J=5.1,3.0Hz,1H),6.06(d,J=7.6Hz,1H),5.30 –5.27(m,1H),5.00–4.95(m,1H),4.59(m,1H),4.31(dd,J=12.1,5.0Hz,1H),4.22–4.15(m,2H),2.16(s,3H),2.09(s,3H),1.96(s,3H). 13C NMR (150MHz, CDCl3) δ170.58,169.43,169.37,162.58,130.96,127.30,126.63 ,93.09,75.56,70.46,67.88,67.17,63.11,20.78,20.69,20.52.HRMS(ESI):C 17 H 20 NO8S[M+H] + Calculated value: 398.0904, measured value: 398.0917.

[0144] Example II-12 Preparation of Compound II-12

[0145]

[0146] 2-Chlorobenzonitrile (68.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 74.4 mg of a transparent oily product with a yield of 35%. 1H NMR(500MHz, CDCl3)δ7.8(dd,J=7.7,1.7Hz,1H),7.5–7.4(m,2H),7.4(td,J=7.5,1 .4Hz,1H),6.1(d,J=7.8Hz,1H),5.3(t,J=4.1Hz,1H),5.0(ddd,J=8.7,4.5,0.9Hz, 1H),4.6(ddd,J=7.8,3.7,0.9Hz,1H),4.3(dd,J=12.1,5.2Hz,1H),4.2(dd,J=12.1 ,2.8Hz,1H),3.8(ddd,J=8.4,5.2,2.8Hz,1H),2.2(s,3H),2.1(s,3H),2.0(s,3H). 13 C NMR (125MHz, CDCl3) δ170.2,169.1,168.9,164.7,133.5,132.2,131.2,130.6,1 26.2,125.4,93.0,70.1,67.6,66.8,62.7,59.9,20.4,20.3,20.2.HRMS (ESI): C 19 H 21 ClNO8[M+H] + Calculated value: 426.095, measured value: 426.0958.

[0147] Example II-13 Preparation of Compound II-13

[0148]

[0149] 2-Bromobenzonitrile (91.0 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 84.5 mg of a transparent oily product with a yield of 38%. 1 H NMR (600MHz, CDCl3) δ7.8 (dd, J=7.6, 1.9Hz, 1H), 7.7 (dd, J=7.9, 1.3Hz, 1H), 7.4 (dtd, J=22.4,7.5,1.6Hz,2H),6.1(d,J=7.8Hz,1H),5.3(t,J=4.2Hz,1H),5.0(ddd,J=8.8,4. 6,0.8Hz,1H),4.7(ddd,J=7.9,3.8,0.8Hz,1H),4.3(dd,J=12.2,5.2Hz,1H),4.2(dd,J= 12.1, 2.8Hz, 1H), 3.9 (ddd, J=8.3, 5.2, 2.7Hz, 1H), 2.2 (s, 3H), 2.1 (s, 3H), 2.0 (s, 3H). 13 C NMR (150MHz, CDCl3) δ170.7,169.6,169.4,165.8,134.3,132.7,131.7,128.0,1 27.3,122.2,93.4,75.9,70.7,68.1,67.4,63.2,20.9,20.8,20.7.HRMS (ESI): C 19 H 21 BrNO8[M+H] + Calculated value: 470.0455, measured value: 470.0457.

[0150] Example II-14 Preparation of Compound II-14

[0151]

[0152] 2-Iodobenzonitrile (114.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 142.9 mg of a transparent oily product with a yield of 56%. 1H NMR (500MHz, CDCl3) δ8.0 (dd, J=8.0, 1.2Hz, 1H), 7.8 (dd, J=7.7, 1.7Hz, 1H), 7.5 (td, J=7.6, 1.2Hz,1H),7.2(td,J=7.7,1.7Hz,1H),6.2(d,J=7.8Hz,1H),5.4(t,J=4.1Hz,1H),5.0(ddd, J=8.8,4.7,0.9Hz,1H),4.7(ddd,J=7.8,3.7,0.9Hz,1H),4.4(dd,J=12.1,5.2Hz,1H),4.3(d d,J=12.2,2.8Hz,1H),3.9(ddd,J=8.4,5.2,2.8Hz,1H),2.2(s,3H),2.1(s,3H),2.0(s,3H). 13 C NMR (125MHz, CDCl3) δ170.7,169.6,169.4,166.5,141.2,132.6,131.6,131.2, 128.0,94.7,93.4,76.1,70.7,68.2,67.4,63.1,20.8,20.8,20.7.HRMS (ESI): C 19 H 21 INO8[M+H] + Calculated value: 518.0306, measured value: 518.0317.

[0153] Example II-15 Preparation of Compound II-15

[0154]

[0155] 2-Chloro-3-methoxybenzonitrile (110.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 54.0 mg of a transparent oily product with a yield of 24%. 1H NMR (600MHz, CDCl3) δ7.38 (dd, J=7.8, 1.4Hz, 1H), 7.31 (t, J=8.0Hz, 1H), 7.09 (dd, J=8.3,1.4Hz,1H),6.12(d,J=7.8Hz,1H),5.33(t,J=4.0Hz,1H),4.98(dd,J=8.8,4 .3Hz,1H),4.63(dd,J=7.9,3.7Hz,1H),4.31(dd,J=12.2,5.3Hz,1H),4.21(dd,J=1 2.2,2.7Hz,1H),3.94(s,3H),3.84(s,1H),2.15(s,3H),2.09(s,3H),2.01(s,3H). 13 C NMR (150MHz, CDCl3) δ170.69,169.58,169.36,165.45,127.28,122.99,114.84,93 .29,75.59,70.45,67.95,67.35,63.23,56.53,20.83,20.78,20.68.HRMS(ESI):C 20 H 23 ClNO9[M+H] + Calculated value: 456.1056, measured value: 456.1060.

[0156] Example II-16 Preparation of Compound II-16

[0157]

[0158] 2-Bromo-3-methoxybenzonitrile (105.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 116.8 mg of a transparent oily product with a yield of 47%. 1 H NMR(500MHz, CDCl3)δ7.36(t,J=8.0Hz,1H),7.32–7.29(m,1H),7.05(dd,J=8.1,1.6Hz,1H),6.12(d,J=7.8Hz,1H),5.36(t,J=4.0Hz,1H),4.99 (m,1H),4.65(m,1H),4.32(dd,J=12.1,5.3Hz,1H),4.22(dd,J=12.1,2.7Hz,1H),3.93(d,J=7.9Hz,4H),2.15(s,3H),2.09(s,3H),2.04(s,3H). 13C NMR (125MHz, CDCl3) δ170.66,169.56,169.33,166.22,156.62,128.17,123.22,114.52,9 3.28,75.96,70.70,68.00,67.42,63.15,60.34,56.61,20.78,20.73,20.66.HRMS (ESI): C 20 H 23 BrNO9[M+H] + Calculated value: 500.0551, measured value: 500.0556.

[0159] Example II-17 Preparation of Compound II-17

[0160]

[0161] 2-Chloro-4-methoxybenzonitrile (83.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 151.2 mg of a transparent oily product with a yield of 67%. 1 H NMR (500MHz, CDCl3) δ7.85(d,J=8.8Hz,1H),7.04(d,J=2.5Hz,1H),6.88(dd,J=8.8,2.5Hz,1H),6.13(d,J=7.7Hz,1H),5.37–5.31(m,1H),5.00(m ,1H),4.61(m,1H),4.33(dd,J=12.1,5.2Hz,1H),4.23(dd,J=12.1,2.9H z,1H),3.88(s,3H),3.83(m,1H),2.17(s,3H),2.11(s,3H),2.01(s,3H). 13 C NMR (125MHz, CDCl3) δ170.67,169.55,169.41,164.86,162.48,135.50,133.03,117.76,116.4 0,112.81,93.44,75.29,70.60,68.05,67.33,63.25,55.72,20.84,20.77,20.65.HRMS (ESI): C 20 H 23 ClNO9[M+H] + Calculated value: 456.1056, measured value: 456.1049.

[0162] Example II-18 Preparation of Compound II-18

[0163]

[0164] 2-Bromo-4-methoxybenzonitrile (105.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 110.0 mg of a transparent oily product with a yield of 44%. 1 H NMR (600MHz, CDCl3) δ7.78(d,J=8.8Hz,1H),7.23(d,J=2.5Hz,1H),6.91(dd,J=8.8,2.5Hz,1H),6.11(d,J=7.8Hz,1H),5.33(t,J=4.2Hz,1H),4.98 (m,1H),4.63–4.58(m,1H),4.32(dd,J=12.1,5.2Hz,1H),4.21(dd,J=12. 1,2.7Hz,1H),3.87–3.83(m,4H),2.16(s,3H),2.10(s,3H),2.00(s,3H). 13 C NMR (150MHz, CDCl3) δ170.70,169.58,169.43,162.24,133.05,123.34,119.76,11 3.26,93.41,70.65,68.04,67.37,63.22,55.73,20.86,20.80,20.69.HRMS(ESI):C 20 H 23 BrNO9[M+H] + Calculated value: 500.0551, measured value: 500.0558.

[0165] Example II-19 Preparation of Compound II-19

[0166]

[0167] 2-Bromo-5-methoxybenzonitrile (105.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 123.0 mg of a transparent oily product with a yield of 50%. 1H NMR (500MHz, CDCl3) δ7.57(d,J=8.9Hz,1H),7.33(d,J=3.1Hz,1H),6.93(dd,J=8.9,3.1Hz,1H),6.14(d,J=7.8Hz,1H),5.36(t,J=4.2Hz,1H),5.00 (m,1H),4.66(m,1H),4.34(dd,J=12.2,5.2Hz,1H),4.23(dd,J=12.2,2.8 Hz,1H),3.88(m,1H),3.84(s,3H),2.16(s,3H),2.10(s,3H),2.02(s,3H). 13 C NMR (126MHz, CDCl3) δ170.66,169.55,169.37,158.57,135.05,119.21,116.64,112.37,93.4 0,77.24,76.02,70.72,68.15,67.31,63.13,60.36,55.68,20.82,20.76,20.67.HRMS (ESI): C 20 H 23 BrNO9[M+H] + Calculated value: 500.0551, measured value: 500.0556.

[0168] Example II-20 Preparation of Compound II-20

[0169]

[0170] 2-Bromopiperonitrile (112.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 139.3 mg of a transparent oily product with a yield of 54%. 1 H NMR (500MHz, CDCl3) δ7.28 (s, 1H), 7.13 (s, 1H), 6.12 (d, J = 7.8Hz, 1H), 6.07 (s,2H),5.33(t,J=4.2Hz,1H),4.99(m,J=8.7,4.6,0.8Hz,1H),4.62(m,J=7 .8,3.7,0.9Hz,1H),4.33(dd,J=12.2,5.2Hz,1H),4.22(dd,J=12.2,2.8Hz, 1H),3.84(m,J=8.3,5.2,2.7Hz,1H),2.16(s,3H),2.10(s,3H),2.03(s,3H). 13C NMR (125MHz, CDCl3) δ170.68,169.55,169.38,165.46,150.97,147.25,128.36,114.32,11 0.99,102.56,93.29,75.71,70.61,68.08,67.35,63.19,20.81,20.76,20.68.HRMS (ESI): C 20 H 21 BrNO 10 [M+H] + Calculated value: 514.0343, measured value: 514.0354.

[0171] Example II-21 Preparation of Compound II-21

[0172]

[0173] Piperonitrile (73.5 mg, 0.5 mmol) and β-D-galactose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 97.7 mg of a transparent oily product with a yield of 45%. 1 H NMR (500MHz, CDCl3) δ7.50(dd,J=8.1,1.7Hz,1H),7.37(d,J=1.7Hz,1H),6.78(d,J=8.1Hz,1H),6.03–5.93(m,3H),5.41(s ,1H),4.98(dd,J=7.2,3.1Hz,1H),4.61(t,J=7.1Hz,1H),4.22(m,1H),4.13(m,2H),2.10(s,3H),2.06(s,3H),2.00(s,3H). 13 C NMR (125MHz, CDCl3) δ169.98,169.53,169.51,165.17,150.85,147.32,123.75,119.90,108.19 ,107.72,101.32,93.63,76.17,71.33,68.80,65.72,60.88,20.29,20.22,20.15.HRMS (ESI): C 20 H 22 NO 10 [M+H] + Calculated value: 436.1238, measured value: 436.1247.

[0174] Example II-22 Preparation of Compound II-22

[0175]

[0176] Piperonitrile (73.5 mg, 0.5 mmol) and α-D-mannose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 132.0 mg of a transparent oily product with a yield of 61%. 1 H NMR (600MHz, CDCl3) δ7.62 (dd, J=8.2, 1.7Hz, 1H), 7.49 (d, J=1.6Hz, 1H), 6.86 ( d,J=8.2Hz,1H),6.05(s,2H),5.74(d,J=5.5Hz,1H),5.40(dd,J=8.4,4.9Hz,1H) ,5.14(t,J=8.2Hz,1H),4.81(t,J=5.2Hz,1H),4.24(dd,J=12.0,6.4Hz,1H),4. 16(dd,J=12.0,3.4Hz,1H),3.83(m,1H),2.12(s,3H),2.08(s,3H),2.04(s,3H). 13 C NMR (125MHz, CDCl3) δ170.30,169.76,168.95,167.85,151.03,147.36,124.17,119.55,108 .52,107.79,101.35,93.19,76.32,72.86,68.52,66.09,63.27,20.29,20.27.HRMS (ESI): C 20 H 22 NO 10 [M+H] + Calculated value: 436.1238, measured value: 436.1238.

[0177] Example II-23 Preparation of Compound II-23

[0178]

[0179] 2-Bromo-3,4,5-trimethoxybenzonitrile (135.5 mg, 0.5 mmol) and α-D-mannose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 63.9 mg of a transparent oily product with a yield of 23%. 1H NMR (600MHz, CDCl3) δ7.24(s,1H),6.40(d,J=6.2Hz,1H),5.39(d,J=1.2Hz,1H),5.01(d,J=6.2Hz,1H),4.95(m,1H),4.46(dd,J=12.3,2.6 Hz,1H),4.31(t,J=6.7Hz,1H),4.25(dd,J=7.1,5.1Hz,1H),3.94(s,3H),3.92(s,3H),3.89(s,3H),2.15(s,3H),2.09(s,3H),2.05(s,3H). 13 C NMR (125MHz, CDCl3) δ171.87,171.56,170.92,167.13,154.11,153.03,147.40,132.31,124 .44,111.73,104.31,87.02,83.62,79.64,70.71,64.19,62.59,62.47,57.81,22.26,22.16. HRMS(ESI):C 22 H 27 BrNO 11 [M+H] + Calculated value: 560.0762, measured value: 560.0764.

[0180] Example II-24 Preparation of Compound II-24

[0181]

[0182] 2-Bromo-3,4,5-trimethoxybenzonitrile (135.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 121.4 mg of a clear oily product with a yield of 44%. 1 H NMR (500MHz, CDCl3) δ7.17(s,1H),6.10(d,J=7.7Hz,1H),5.37–5.35(m,1H),5.00(dd,J=9.2,4.8Hz,1H),4.63(dd,J=7 .8,4.0Hz,1H),4.36–4.29(m,2H),4.23–4.19(m,1H),3.94(s,3H),3.90(s,6H),2.15(s,3H),2.10(s,3H),2.02(s,3H). 13C NMR (125MHz, CDCl3) δ170.20,169.07,168.97,165.31,152.08,145.62,122.64,110.06,9 2.96,70.63,67.62,66.83,62.52,60.72,60.59,55.84,20.36,20.31,20.22.HRMS (ESI): C 22 H 27 BrNO 11 [M+H] + Calculated value: 560.0762, measured value: 560.0761.

[0183] Example II-25 Preparation of Compound II-25

[0184]

[0185] Benzonitrile (51.5 mg, 0.5 mmol) and 5-deoxy-1,2,3-triacetyl ribofuranose (130 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 129.5 mg of a transparent oily product with a yield of 50%. 1 H NMR(500MHz, CDCl3)δ8.07–7.95(m,2H),7.52(m,1H),7.49–7.39(m,2H),6.18(d,J=5.6Hz,1H),5.17 (t,J=5.6Hz,1H),4.49(dd,J=9.3,5.6Hz,1H),3.80–3.69(m,1H),2.15(s,3H),1.32(d,J=6.1Hz,3H). 13 C NMR (125MHz, CDCl3) δ170.34,167.25,132.35,128.85,128.52,128.44,126.21,100.00,78.46,78.23,71.61,20.54,16.60.HRMS (ESI): C 14 H 16 NO4[M+H] + Calculated value: 262.1074, measured value: 262.1075.

[0186] Example II-26 Preparation of Compound II-26

[0187]

[0188] Benzonitrile (51.5 mg, 0.5 mmol) and β-D-ribofuranose tetraacetate (159 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 129.5 mg of a transparent oily product with a yield of 81%. 1 H NMR (600MHz, CDCl3) δ8.04(m,4H),7.57(m,2H),7.47(m,4H),6.33(d,J=6.1Hz,1H),6. 29(d,J=5.6Hz,1H),5.34(m,1H),5.24(t,J=5.7Hz,1H),5.06(dd,J=6.2,1.0Hz,1H),4. 87(dd,J=9.3,5.9Hz,1H),4.43(dd,J=12.4,2.7Hz,1H),4.33(m,1H),4.23(dd,J=12.4, 5.0Hz,1H),4.07(m,2H),3.92(m,1H),2.18(d,J=5.8Hz,6H),2.11(s,3H),1.91(s,3H). 13 C NMR (125MHz, CDCl3) δ170.7,170.1,167.5,132.5,129.0,128.9,128.6,128.5,126.1,100.7,78.1,74.0,73.0,62.0,20.8,20.5.HRMS (ESI): C 14 H 16 NO4[M+H] + Calculated value: 320.1129, measured value: 320.1128.

[0189] Example II-27 Preparation of Compound II-27

[0190]

[0191] Piperononitrile (73.5 mg, 0.5 mmol) and 5-deoxy-1,2,3-triacetyl ribofuranose (130 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 77.5 mg of a transparent oily product with a yield of 51%. 1H NMR (500MHz, CDCl3) δ7.7(ddd,J=8.2,3.1,1.7Hz,1H),7.5(dd,J=4.1,1.7Hz,1H),6.9(d,J=8.2Hz,1H),6.1(s,2H),5 .6–5.4(m,1H),5.4–5.3(m,1H),5.3–5.1(m,1H),4.5–4.3(m,1H),2.1(d,J=46.9Hz,3H),1.4(dd,J=35.9,6.4Hz,3H). 13 C NMR (125MHz, CDCl3) δ170.0,164.8,152.1,147.8,125.7,123.2,109.5,108.1,101.9,100.1,95.4,76.4,75.0,20.6,20.3.HRMS (ESI): C 15 H 16 NO6[M+H] + Calculated value: 306.0972, measured value: 306.0978.

[0192] Example II-28 Preparation of Compound II-28

[0193]

[0194] 2-Chlorobenzonitrile (68.5 mg, 0.5 mmol) and β-D-ribofuranose tetraacetate (159 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 126.0 mg of a transparent oily product with a yield of 71%. 1 H NMR (500MHz, CDCl3) δ7.84 (dd, J=7.8, 1.7Hz, 1H), 7.50 (dd, J=8.0, 1.4Hz, 1H) ,7.45(td,J=8.1,7.7,1.7Hz,1H),7.35(td,J=7.5,1.4Hz,1H),6.32(d,J=5.7H z,1H),5.26(t,J=5.8Hz,1H),4.86(dd,J=9.4,5.8Hz,1H),4.46(dd,J=12.3,2. 7Hz, 1H), 4.26 (dd, J = 12.3, 5.1Hz, 1H), 4.02 (m, 1H), 2.16 (s, 3H), 2.12 (s, 3H). 13C NMR (125MHz, CDCl3) δ170.67,170.09,133.71,132.50,131.73,130.91,126.66,100.61,78.20,74.00,73.01,61.93,20.76,20.52.HRMS (ESI): C 16 H 17 ClNO6[M+H] + Calculated value: 354.0739, measured value: 354.0742.

[0195] Example II-29 Preparation of Compound II-29

[0196]

[0197] 2-Bromobenzonitrile (90.5 mg, 0.5 mmol) and β-D-ribofuranose tetraacetate (159 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 156.0 mg of a transparent oily product with a yield of 79%. 1 H NMR (500MHz, CDCl3) δ7.79–7.73(m,1H),7.68(dd,J=7.7,1.5Hz,1H),7.37(m,2H),6.30(d,J=5.7Hz,1H),5.25(t,J=5.8Hz,1H), 4.86(dd,J=9.5,5.8Hz,1H),4.45(dd,J=12.4,2.7Hz,1H),4.25(dd,J=12.4,5.0Hz,1H),4.06(m,1H),2.15(s,3H),2.11(s,3H). 13 C NMR (125MHz, CDCl3) δ170.65,170.07,167.24,134.10,132.49,131.78,128.44, 127.20,121.78,100.57,78.37,74.00,73.03,61.93,20.76,20.57.HRMS(ESI):C 16 H 17 BrNO6[M+H] + Calculated value: 398.0234, measured value: 398.0229.

[0198] Example II-30 Preparation of Compound II-30

[0199]

[0200] 2-Iodobenzonitrile (114.5 mg, 0.5 mmol) and β-D-ribofuranose tetraacetate (159 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain 142.6 mg of a transparent oily product with a yield of 64%. 1 H NMR (500MHz, CDCl3) δ7.99 (dd, J=7.9, 1.1Hz, 1H), 7.71 (dd, J=7.8, 1.7Hz, 1H), 7.42(td,J=7.6,1.2Hz,1H),7.17(td,J=7.7,1.7Hz,1H),6.30(d,J=5.7Hz,1H) ,5.25(t,J=5.7Hz,1H),4.88(dd,J=9.5,5.7Hz,1H),4.45(dd,J=12.3,2.7Hz,1 H),4.25(dd,J=12.4,5.0Hz,1H),4.17–4.08(m,1H),2.15(s,3H),2.11(s,3H). 13 C NMR (125MHz, CDCl3) δ170.64,170.05,167.93,140.95,132.43,131.32,127 .88,100.57,94.27,78.44,74.06,73.07,61.96,20.77,20.68.HRMS(ESI):C 16 H 17 INO6[M+H] + Calculated value: 446.0095, measured value: 446.0094.

[0201] Example II-31 Preparation of Compound II-31

[0202]

[0203] Piperononitrile (73.5 mg, 0.5 mmol) and D-(+)-cellobiose octaacetate (339 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 151.1 mg of a transparent oily product with a yield of 42%. 1H NMR (600MHz, CDCl3) δ7.61(dd,J=8.2,1.7Hz,1H),7.48(d,J=1.7Hz,1H),6.88(d,J=8.1Hz,1H),6.05(s,2H),5.97(d,J=7. 4Hz,1H),5.63(s,1H),5.19–5.08(m,2H),4.89(dd,J=9.3,8.0Hz,1H),4.66(d,J=8.1Hz,1H),4.54(ddd,J=7.4,3.3,1.1Hz, 1H),4.26(dd,J=12.3,4.4Hz,1H),4.22(dd,J=12.0,2.5Hz,1H),4.17(dd,J=12.3,2.6Hz,1H),4.15–4.11(m,1H),3.76–3.6 6(m,2H),3.46(ddd,J=9.0,5.1,2.5Hz,1H),2.15(s,3H),2.12(s,3H),2.11(s,3H),2.02(s,3H),1.97(s,3H),1.97(s,3H). 13 C NMR (150MHz, CDCl3) δ170.54,170.10,169.28,169.26,169.11,166.80,151.33,147.73,124.45,119.66,108.86,108.22,101.67,10 1.54,92.45,75.35,72.84,71.84,71.21,69.76,67.99,67.21,63.48,61.64,20.82,20.77,20.62,20.48,20.45,20.34.HRMS (ESI): C 32 H 38 NO 18 [M+H] + Calculated value: 724.2083, measured value: 724.2100.

[0204] Example II-32 Preparation of Compound II-32

[0205]

[0206] Piperonitrile (73.5 mg, 0.5 mmol) and maltotriose undecanoate (483 mg, 0.5 mmol) were synthesized according to the method described in II-1 to obtain a total of 91.1 mg of white powder product with a yield of 18%. 1H NMR (500MHz, CDCl3) δ7.68(dd,J=8.1,1.7Hz,1H),7.55(d,J=1.7Hz,1H),6.97(d,J=8.2Hz,1H),6.05(d,J=1.5Hz,2H),5.39(d,J= 4.0Hz,1H),5.36–5.29(m,3H),5.24(dd,J=3.4,1.6Hz,1H),5.07(d,J=9.9Hz,1H),4.85(ddd,J=15.8,10.3,4.0Hz,2H),4.59–4.54 (m,1H),4.43(dd,J=12.4,1.8Hz,1H),4.31–4.21(m,4H),4.18–4.13(m,1H),4.07–4.03(m,1H),3.93(dd,J=7.1,2.5Hz,3H),3.72( dt,J=8.6,1.7Hz,1H),3.61(td,J=5.3,2.6Hz,1H),2.16(s,6H),2.14(s,6H),2.11(s,3H),2.04(s,6H),2.01(s,3H),2.00(s,3H). 13 C NMR (125MHz, CDCl3) δ170.67,170.50,170.48,170.40,170.21,169.83,169.63,169 .51,169.42,167.24,151.37,147.89,124.62,119.85,108.99,108.63,101.66,95. 77,95.55,92.32,74.82,73.86,72.85,72.05,70.68,70.04,69.42,68.88,68.58,6 8.52,67.88,67.39,64.01,62.55,61.41,20.90,20.69,20.66,20.57.HRMS(ESI):C 44 H 53 NNaO 26 [M+Na] + Calculated value: 1034.2748, measured value: 1034.2722.

[0207] The following is an example of preparing the compound of formula III

[0208]

[0209] Example III-1 Preparation of Compound III-1

[0210]

[0211] Method 1: Dissolve β-D-glucose pentaacetate (195 mg, 0.5 mmol) in a dry round-bottom flask containing 10 ml of ultra-dry dichloromethane. Add benzonitrile (50 μl, 0.5 mmol) and trifluoromethanesulfonic acid (135 μl, 1.5 mmol) and allow to react for 2 hours. After completion, quench the reaction with deionized water (20 ml) and extract the solution twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. After drying on a rotary evaporator, the product was redissolved in dichloromethane, mixed with silica gel, and separated by silica gel column chromatography using a PE:EA ratio of 3:1 to yield 98.5 mg of the product as a slightly yellowish oil (a white solid precipitated upon refrigeration). The yield was 60%. 1 H NMR(600MHz, CDCl3)δ8.13–8.06(m,2H),7.61–7.52(m,1H),7.51–7.42(m,2H),6.63(dd,J=10.4,2.6Hz,1H),6.2 9(dd,J=10.4,1.8Hz,1H),5.77(d,J=1.0Hz,1H),4.59–4.50(m,1H),4.27–4.17(m,2H),2.08(s,3H),2.06(s,3H). 13 C NMR (125MHz, CDCl3) δ170.83,168.74,167.19,134.83,132.82,129.19,128. 48,126.20,122.07,101.40,96.82,69.72,65.17,21.66,20.81.HRMS(ESI):C 17 H 18 NO6[M+H] + Calculated value: 332.1129, measured value: 332.1123.

[0212] Method 2: Benzonitrile (51.5 mg, 0.5 mmol) and β-D-galactose pentaacetate (195 mg, 0.5 mmol) were synthesized as described for compound III-1 to give 129.7 mg of a yellow oily product in 79% yield. 1H NMR (500MHz, CDCl3) δ8.09–8.02(m,2H),7.55–7.48(m,1H),7.45–7.38(m,2H),6.60(dd,J=10.4,2.6Hz,1H),6.2 6(dd,J=10.4,1.9Hz,1H),5.73(d,J=0.8Hz,1H),4.54–4.47(m,1H),4.24–4.14(m,2H),2.04(s,3H),2.03(s,3H). 13 C NMR (125MHz, CDCl3) δ170.35,168.27,166.70,134.38,132.37,128.70,128. 02,125.71,121.57,100.92,96.33,69.24,64.70,21.20,20.34.HRMS(ESI):C 17 H 18 NO6[M+H] + Calculated value: 332.1129, measured value: 332.1138.

[0213] Method 3: Benzonitrile (51.5 mg, 0.5 mmol) and α-D-pentaacetylmannose (195 mg, 0.5 mmol) were synthesized as described for compound III-1 to give 62.4 mg of a yellow oily product in 38% yield. 1 H NMR (500MHz, CDCl3) δ8.10 (dd, J=8.2, 1.4Hz, 2H), 7.61–7.53 (m, 1H), 7.46 (t, J=7.6Hz, 2H), 6. 64(dd,J=10.4,2.6Hz,1H),6.31(dd,J=10.4,1.8Hz,1H),5.78(d,J=1.0Hz,1H),4.55(m,J=6.8, 4.7,2.1Hz,1H),4.29–4.18(m,2H),2.09(s,3H),2.07(s,3H). 13 C NMR (125MHz, CDCl3) δ170.83,168.74,167.20,134.84,132.83,129.19,128. 49,126.20,122.06,101.40,96.81,69.71,65.17,21.66,20.81.HRMS(ESI):C 17 H 18 NO6[M+H] + Calculated value: 332.1129, measured value: 332.1123.

[0214] Example III-2 Preparation of Compound III-2

[0215]

[0216] 2-Methylbenzonitrile (58.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 83.1 mg of a clear oily product with a yield of 48%. 1 H NMR (400MHz, CDCl3) δ8.01–7.96(m,1H),7.42(m,1H),7.30(d,J=3.0Hz,1H),7.26(d,J=7.8Hz,1H),6.64(dd,J=10.4,2.6Hz,1H),6. 30(dd,J=10.4,1.9Hz,1H),5.79(d,J=0.8Hz,1H),4.54(d,J=5.9Hz,1H),4.30–4.19(m,2H),2.70(s,3H),2.10(s,3H),2.09(s,3H). 13 C NMR (125MHz, CDCl3) δ170.83,168.81,167.41,140.41,134.70,131.96,131.57,130.77, 125.71,125.22,122.14,100.49,97.13,69.73,65.20,22.23,21.69,20.83.HRMS(ESI):C 18 H 20 NO6[M+H] + Calculated value: 346.1285, measured value: 346.1292.

[0217] Example III-3 Preparation of Compound III-3

[0218]

[0219] 4-Methoxybenzonitrile (66.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 117.3 mg of yellow oily product with a yield of 65%. 1H NMR (500MHz, CDCl3) δ8.01(d,J=8.9Hz,2H),6.92(d,J=9.0Hz,2H),6.60(dd,J=10.4,2.6Hz,1H),6.26(dd,J =10.4,1.8Hz,1H),5.71(d,J=0.9Hz,1H),4.50(m,1H),4.23(s,2H),3.84(s,3H),2.05(s,3H),2.03(s,3H). 13 C NMR (125MHz, CDCl3) δ170.39,168.35,166.67,162.85,134.36,130.68,121.67, 117.98,113.42,100.91,96.32,69.21,64.72,54.99,21.23,20.37.HRMS(ESI):C 18 H 20 NO7[M+H] + Calculated value: 362.1234, measured value: 362.1232.

[0220] Example III-4 Preparation of Compound III-4

[0221]

[0222] 3-Methoxybenzonitrile (66.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 88.1 mg of yellow oily product with a yield of 49%. 1 H NMR (500MHz, CDCl3) δ7.70–7.62(m,2H),7.37(t,J=8.0Hz,1H),7.12(dd,J=8.3,2.1Hz,1H),6.63(dd,J=10.4,2.6Hz,1H),6. 31(dd,J=10.4,1.8Hz,1H),5.78(s,1H),4.59–4.52(m,1H),4.24(qd,J=11.7,5.5Hz,2H),3.87(s,3H),2.09(d,J=9.3Hz,6H). 13C NMR (125MHz, CDCl3) δ170.85,168.74,167.20,159.57,134.86,129.57,127.39,122.06, 121.68,119.91,113.16,101.47,96.74,69.73,65.17,55.50,21.66,20.81.HRMS(ESI):C 18 H 20 NO7[M+H] + Calculated value: 362.1234, measured value: 362.1226.

[0223] Example III-5 Preparation of Compound III-5

[0224]

[0225] 3,4,5-Trimethoxybenzonitrile (96.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 192.0 mg of yellow oily product with a yield of 91%. 1 H NMR (500MHz, CDCl3) δ7.33(s,2H),6.60(dd,J=10.4,2.6Hz,1H),6.30(dd,J=10.4,1.8Hz,1H),5.75(d,J=0.5Hz,1H ),4.54(ddd,J=6.3,3.7,2.4Hz,1H),4.22(qd,J=11.7,5.5Hz,2H),3.90(d,J=4.7Hz,9H),2.07(d,J=6.7Hz,6H).13C NMR (125MHz, CDCl3) δ170.80,168.71,167.07,153.09,142.14,134.95,121.99,121 .13,106.38,101.60,96.65,69.71,65.14,60.95,56.31,21.65,20.79.HRMS(ESI):C 20 H 24 NO9[M+H] + Calculated value: 422.1455, measured value: 422.1446.

[0226] Example III-6 Preparation of Compound III-6

[0227]

[0228] 4-Fluorobenzonitrile (60.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 41.7 mg of yellow oily product with a yield of 24%. 1 H NMR (500MHz, CDCl3) δ8.12–8.04(m,2H),7.12(dd,J=9.6,7.6Hz,2H),6.60(dd,J=10.4,2.6Hz,1H), 6.29(dd,J=10.4,1.9Hz,1H),5.74(d,J=0.9Hz,1H),4.52(m,1H),4.25–4.16(m,2H),2.06(s,3H),2.05(s,3H). 13 C NMR (125MHz, CDCl3) δ170.74,168.66,166.19,134.91,131.65,131.58,121. 95,115.83,115.66,101.48,96.82,69.70,65.11,21.61,20.76.HRMS(ESI):C 17 H 17 FNO6[M+H] + Calculated value: 350.1034, measured value: 350.1043.

[0229] Example III-7 Preparation of Compound III-7

[0230]

[0231] 4-Chlorobenzonitrile (68.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 54.2 mg of yellow oily product with a yield of 30%. 1 H NMR (500MHz, CDCl3) δ8.03(d,J=8.6Hz,2H),7.44(d,J=8.6Hz,2H),6.62(dd,J=10.4,2.6Hz,1H),6.31(dd, J=10.4,1.8Hz,1H),5.76(d,J=0.8Hz,1H),4.58–4.50(m,1H),4.28–4.18(m,2H),2.09(s,3H),2.07(s,3H). 13C NMR (125MHz, CDCl3) δ170.78,168.67,166.29,139.22,134.93,130.50,128. 86,124.71,121.95,101.50,96.83,69.74,65.11,21.64,20.80.HRMS(ESI):C 17 H 17 ClNO6[M+H] + Calculated value: 366.0739, measured value: 366.0741.

[0232] Example III-8 Preparation of Compound III-8

[0233]

[0234] 4-Bromobenzonitrile (91.0 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 107.4 mg of yellow oily product with a yield of 53%. 1 H NMR (500MHz, CDCl3) δ7.95(d,J=8.6Hz,2H),7.60(d,J=8.6Hz,2H),6.62(dd,J=10.4,2.6Hz,1H),6.30(dd,J=10.4, 1.9Hz,1H),5.76(d,J=0.9Hz,1H),4.54(ddt,J=6.8,4.5,2.0Hz,1H),4.27–4.18(m,2H),2.08(s,3H),2.07(s,3H). 13 C NMR (125MHz, CDCl3) δ170.78,168.66,166.40,134.94,131.84,130.62,127. 82,125.16,121.94,101.50,96.83,69.74,65.11,21.64,20.80.HRMS(ESI):C 17 H 17 BrNO6[M+H] + Calculated value: 410.0234, measured value: 410.0237.

[0235] Example III-9 Preparation of Compound III-9

[0236]

[0237] 4-Trifluoromethylbenzonitrile (85.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 68.4 mg of yellow oily product with a yield of 34%. 1 H NMR (500MHz, CDCl3) δ8.20(d,J=8.2Hz,2H),7.72(d,J=8.3Hz,2H),6.63(dd,J=10.4,2.6Hz,1H),6.3 2(dd,J=10.4,1.8Hz,1H),5.79(s,1H),4.59–4.51(m,1H),4.29–4.17(m,2H),2.08(d,J=3.6Hz,6H). 13 C NMR (125MHz, CDCl3) δ170.28,168.13,165.35,134.51,129.06,124.97,121.35,101.05,96.29,69.28,64.58,21.09,20.26.HRMS(ESI):C 18 H 17 F3NO6[M+H] + Calculated value: 400.1002, measured value: 400.1006.

[0238] Example III-10 Preparation of Compound III-10

[0239]

[0240] 4-Ethynylbenzonitrile (63.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give 37.6 mg of a yellow oily product in a 32% yield. 1H NMR (500 MHz, CDCl3) δ 8.08–8.02 (m, 2H), 7.61–7.54 (m, 2H), 6.63 (dd, J = 10.4, 2.6 Hz, 1H), 6.30 (dd, J = 10.4, 1.8 Hz, 1H), 5.78 (s, J = 0.6 Hz, 1H), 4.55 (ddd, J = 5.5, 3.7, 2.4 Hz, 1H), 4.29–4.17 (m, 2H), 3.26 (s, 1H), 2.08 (d, J = 7.3 Hz, 6H). 13C NMR (125MHz, CDCl3) δ170.83,168.71,166.51,134.92,132.16,129.05,126.66,126 .30,121.98,101.47,96.81,82.78,80.24,69.75,65.13,21.65,20.80.HRMS(ESI):C 19 H 18 NO6[M+H] + Calculated value: 356.1129, measured value: 356.1131.

[0241] Example III-11 Preparation of Compound III-11

[0242]

[0243] 2-Chloro-4-methoxybenzonitrile (83.7 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 28.05 mg of yellow oily product with a yield of 14%. 1 H NMR (500MHz, CDCl3) δ7.95(d,J=8.8Hz,1H),7.01(d,J=2.5Hz,1H),6.85(dd,J=8.8,2.5Hz,1H),6.64(dd,J=10.4,2.6Hz,1H),6.29( dd,J=10.4,1.8Hz,1H),5.77(s,1H),4.53(td,J=4.6,2.4Hz,1H),4.24(qd,J=11.7,5.6Hz,2H),3.86(s,3H),2.09(d,J=7.5Hz,6H). 13 CNMR (125MHz, CDCl3) δ170.83,168.79,165.43,162.66,135.98,134.78,133.65,122.02, 117.45,116.51,112.72,100.70,96.90,69.75,65.16,55.73,21.67,20.82.HRMS(ESI):C 18 H 19 ClNO7[M+H] + Calculated value: 396.0845, measured value: 396.0840.

[0244] Example III-12 Preparation of Compound III-12

[0245]

[0246] 2-Bromo-4-methoxybenzonitrile (106.0 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 86.7 mg of yellow oily product with a yield of 40%. 1 H NMR (500MHz, CDCl3) δ7.92(d,J=8.8Hz,1H),7.23(d,J=2.5Hz,1H),6.91(dd,J=8.8,2.5Hz,1H),6.67(dd,J=10.4,2.6Hz,1H),6.30( dd,J=10.4,1.9Hz,1H),5.77(s,1H),4.53(td,J=4.7,2.6Hz,1H),4.25(qd,J=11.6,5.6Hz,2H),3.87(s,3H),2.10(d,J=6.4Hz,6H). 13 CNMR(125MHz, CDCl3)δ170.33,168.30,165.45,161.91,134.24,133.26,123.15,121.55, 119.40,118.99,112.66,100.37,96.41,69.24,64.68,55.22,21.19,20.33.HRMS(ESI):C 18 H 19 BrNO7[M+H] + Calculated value: 440.0339, measured value: 440.0337.

[0247] Example III-13 Preparation of Compound III-13

[0248]

[0249] 4-Cyanobiphenyl (90.0 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 69.01 mg of yellow oily product with a yield of 34%. 1H NMR (500MHz, CDCl3) δ8.19–8.11(m,2H),7.72–7.59(m,4H),7.47(dd,J=10.4,4.7Hz,2H),7.43–7.36(m,1H),6.64(dd,J=10.4,2.6Hz,1H ), 6.30(dd,J=10.4,1.8Hz,1H),5.78(d,J=0.4Hz,1H),4.54(td,J=4.6,2.7Hz,1H),4.23(qd,J=11.7,5.6Hz,2H),2.07(d,J=7.0Hz,6H).

[0250] 13 C NMR (125MHz, CDCl3) δ170.85,168.78,167.09,145.58,139.91,134.87,129.71,128.95,1 28.21,127.19,124.98,122.11,101.45,96.88,69.75,65.20,21.69,20.83.HRMS(ESI):C 23 H 23 NO6[M+H] + Calculated value: 408.1442, measured value: 408.1453.

[0251] Example III-14 Preparation of Compound III-14

[0252]

[0253] 2-Naphthonitrile (76.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 141.0 mg of yellow oily product with a yield of 74%. 1 H NMR(500MHz, CDCl3)δ8.59(t,J=1.1Hz,1H),8.15(dd,J=8.6,1.7Hz,1H),7.95–7.86(m,3H),7.60–7.53(m,2H),6.69(dd,J=10 .4, 2.6Hz, 1H), 6.32 (dd, J=10.4, 1.8Hz, 1H), 5.83 (d, J=0.9Hz, 1H), 4.57 (m, 1H), 4.29–4.19 (m, 2H), 2.08 (s, 6H). 13C NMR (125MHz, CDCl3) δ170.80,168.80,167.31,135.39,134.93,132.46,130.40,129.15,128.34,128. 26,127.83,126.80,124.93,123.45,122.09,101.50,96.89,69.77,65.17,21.69,20.81.HRMS(ESI):C 21 H 20 NO6[M+H] + Calculated value: 382.1285, measured value: 382.1289.

[0254] Example III-15 Preparation of Compound III-15

[0255]

[0256] 2-Cyanofuran (46.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 87.0 mg of yellow oily product with a yield of 54%. 1 H NMR (600MHz, CDCl3) δ7.64(d,J=0.9Hz,1H),7.23(d,J=3.5Hz,1H),6.63–6.50(m,2H),6.30(dd,J=10.4,1.8H z,1H),5.77(s,1H),4.54(td,J=4.4,2.6Hz,1H),4.22(ddd,J=16.1,11.7,5.6Hz,3H),2.08(d,J=6.4Hz,6H). 13 C NMR (150MHz, CDCl3) δ170.76,170.42,168.26,158.63,146.30,141.02,134.54,1 21.25,117.32,111.62,100.90,95.95,69.26,64.63,21.19,20.34.HRMS(ESI):C 15 H 16 NO7[M+H] + Calculated value: 322.0921, measured value: 322.0925.

[0257] Example III-16 Preparation of Compound III-16

[0258]

[0259] 3-Cyanothiophene (46.5 mg, 0.5 mmol) and β-D-glucose pentaacetate (195 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 112.07 mg of yellow oily product with a yield of 67%. 1 H NMR (500MHz, CDCl3) δ8.13(dd,J=3.0,1.1Hz,1H),7.65(dd,J=5.1,1.1Hz,1H),7.38(dd,J=5.1,3.0Hz,1H),6.61(dd,J=10.4,2.6H z,1H),6.30(dd,J=10.4,1.8Hz,1H),5.75(s,1H),4.54(td,J=4.6,2.7Hz,1H),4.23(qd,J=11.7,5.6Hz,2H),2.08(d,J=9.2Hz,6H). 13 C NMR (125MHz, CDCl3) δ170.84,168.75,163.31,134.86,131.68,128.56,127.60( s,3H),126.58,122.02,101.33,96.80,69.73,65.16,21.66,20.81.HRMS(ESI):C 15 H 15 NO6S[M+H] + Calculated value: 338.0693, measured value: 338.0694.

[0260] Example III-17 Preparation of Compound III-17

[0261]

[0262] Benzonitrile (51.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-alpha-L-fucose (165 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 9.5 mg of yellow oily product with a yield of 7%. 1 H NMR(500MHz, CDCl3)δ8.11(dd,J=8.4,1.3Hz,2H),7.60–7.53(m,1H),7.50–7.42(m,2H),6.57(dd,J=10.3,2.5Hz ,1H),6.26(dd,J=10.3,1.6Hz,1H),5.71(d,J=0.7Hz,1H),4.48–4.37(m,1H),2.06(s,3H),1.38(d,J=6.9Hz,3H).13 C NMR (125MHz, CDCl3) δ168.81,167.16,140.20,132.68,129.18,128.43,126.42,119.96,101.50,96.90,67.63,21.71,20.63.HRMS(ESI):C 15 H 16 NO4[M+H] + Calculated value: 274.1074, measured value: 274.1075.

[0263] Example III-18 Preparation of Compound III-18

[0264]

[0265] Piperonitrile (73.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-alpha-L-fucopyranoside (165 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give a total of 45.6 mg of yellow oily product with a yield of 29%. 1 H NMR (500MHz, CDCl3) δ7.66(dd,J=8.2,1.7Hz,1H),7.54(d,J=1.7Hz,1H),6.85(d,J=8.1Hz,1H),6.54(dd,J=10.3,2.5Hz, 1H),6.23(dd,J=10.3,1.6Hz,1H),6.04(s,2H),5.69–5.61(m,1H),4.44–4.33(m,1H),2.05(s,3H),1.36(d,J=6.9Hz,3H). 13 C NMR (125MHz, CDCl3) δ168.79,166.74,151.44,147.76,140.16,124.74,120.21,1 19.94,109.03,108.16,101.75,101.52,96.83,67.58,21.71,20.61.HRMS(ESI):C 16 H 16 NO6[M+H] + Calculated value: 318.0972, measured value: 318.0973.

[0266] Example III-19 Preparation of Compound III-19

[0267]

[0268] Method 1: Benzonitrile (51.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-β-D-ribopyranose acetate (159 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give 43.4 mg of a clear oily product (a:b = 1:1) in a 34% yield. 1 H NMR (500MHz, CDCl3) δ8.10–8.04(m,2H),7.56(dd,J=10.6,4.3Hz,1H),7.46(t,J=7.7Hz,2H),6.50( dt,J=10.5,1.8Hz,1H),6.39(dt,J=10.5,3.3Hz,1H),5.87(s,1H),4.35–4.20(m,2H),2.11(s,3H). 13 C NMR (125MHz, CDCl3) δ168.71,166.64,134.82,132.64,128.98,128.47,126.45,120.78,101.41,97.36,60.89,21.70.HRMS(ESI):C 14 H 14 NO4[M+H] + Calculated value: 260.0917, measured value: 260.0914.

[0269] Method 2: Benzonitrile (51.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-β-D-xylopyranose (159 mg, 0.5 mmol) were synthesized as described for compound III-1 to yield 49.6 mg of a clear oily product (a:b = 1:1) in a 38% yield. 1 H NMR (500MHz, CDCl3) δ8.08–8.01(m,2H),7.58–7.50(m,1H),7.43(dd,J=10.7,4.7Hz,2H),6.48(d t,J=10.5,1.9Hz,1H),6.36(dt,J=10.5,3.3Hz,1H),5.85(s,1H),4.31–4.18(m,2H),2.08(s,3H). 13 C NMR (125MHz, CDCl3) δ168.27,166.19,134.38,132.19,128.53,128.01,125.98,120.31,100.94,96.89,60.44,21.26.HRMS(ESI):C 14 H 14 NO4[M+H] +Calculated value: 260.0917, measured value: 260.0916.

[0270] Example III-20 Preparation of Compound III-20

[0271]

[0272] Method 1: Piperonitrile (73.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-β-D-ribopyranose (159 mg, 0.5 mmol) were synthesized according to the method described for compound III-1 to give 49.8 mg of a clear oily product (a:b = 1:1) in a 33% yield. 1 H NMR(600MHz, CDCl3) δ7.59(dd,J=8.2,1.7Hz,1H),7.47(d,J=1.7Hz,1H),6.82(d,J=8.1Hz,1H), 6.48-6.42(m,1H),6.38-6.32(m,1H),6.02(s,2H),5.78(s,1H),4.26–4.19(m,2H),2.06(s,3H). 13 C NMR (150MHz, CDCl3) δ168.30,165.81,150.94,147.31,134.42,124.07,120.1 9,119.70,108.37,107.73,101.32,100.92,96.72,60.50,21.29.HRMS(ESI):C 15 H 14 NO6[M+H] + Calculated value: 304.0816, measured value: 304.0820.

[0273] Method 2: Piperonitrile (73.5 mg, 0.5 mmol) and 1,2,3,4-tetra-O-acetyl-β-D-xylopyranose (159 mg, 0.5 mmol) were synthesized as described for compound III-1 to yield 84.2 mg of a clear oil (a:b = 1:1) in 56% yield. 1 H NMR(600MHz, CDCl3) δ7.59(dd,J=8.2,1.7Hz,1H),7.47(d,J=1.7Hz,1H),6.82(d,J=8.2Hz,1H), 6.47–6.42(m,1H),6.38–6.31(m,1H),6.01(s,2H),5.77(s,1H),4.26–4.18(m,2H),2.06(s,3H). 13C NMR (150MHz, CDCl3) δ168.26,165.78,150.93,147.31,134.38,124.05,120.2 1,119.72,108.37,107.71,101.31,100.93,96.73,60.45,21.25.HRMS(ESI):C 15 H 14 NO6[M+H] + Calculated value: 304.0816, measured value: 304.0815.

[0274] Example III-21 Preparation of Compound III-21

[0275]

[0276] III-1 (33.1 mg, 0.2 mmol) was dissolved in a round-bottom flask containing 3 ml of thionyl chloride and heated at 60°C under a nitrogen atmosphere for 2 hours. After completion, the reaction was quenched with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were then combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was dried using a rotary evaporator, dissolved in dichloromethane, mixed with silica gel, and separated by column chromatography (PE:EA = 10:1). 15.3 mg of the product was obtained as a yellow oil with a yield of 53%. 1 H NMR (500MHz, CDCl3) δ8.14–8.07(m,2H),7.60(t,J=7.5Hz,1H),7.49(t,J=7.8Hz,2H),7.29(s,1H),6.49(dd,J=10 .1,2.5Hz,1H),6.15(dd,J=10.1,1.6Hz,1H),5.86(s,1H),4.51(t,J=5.4Hz,1H),4.27–4.19(m,2H),2.10(s,3H). 13 C NMR (125MHz, CDCl3) δ170.79,167.16,133.09,131.36,129.26,128.57,125.94,125.23,100.47,96.56,69.83,64.93,53.42,20.79.HRMS(ESI):C 15 H 16 NO5[M+H] + Calculated value: 290.1023, measured value: 290.1018.

[0277] Example III-22 Preparation of Compound III-22

[0278]

[0279] 1,2,3,4,6-penta-O-pivaloyl-D-mannopyranose (300 mg, 0.5 mmol) was dissolved in a dry round-bottom flask containing 10 ml of ultra-dry dichloromethane. After clearing, trifluoromethanesulfonic acid (135 μl, 1.5 mmol) was added and the mixture was heated to 40°C. After 30 minutes, benzonitrile (50 μl, 0.5 mmol) was added and the mixture was allowed to react under nitrogen for 1.5 hours. After completion, the reaction was quenched with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were then combined, washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The mixture was dried on a rotary evaporator and redissolved in dichloromethane. The sample was mixed with silica gel and separated by column chromatography using a PE:EA ratio of 3:1 to obtain 108.2 mg of the product as a brownish-yellow oil in a 52% yield. 1 H NMR (500MHz, CDCl3) δ8.10–8.04(m,2H),7.58–7.53(m,1H),7.44(dd,J=8.4,7.1Hz,2H),6.58(dd,J=10.4,2.5Hz,1H),6.29(dd,J=10. 4,1.7Hz,1H),4.53(dqt,J=7.0,2.8,2.0Hz,1H),4.27(dd,J=11.5,6.0Hz,1H),4.16(dd,J=11.5,5.3Hz,1H),1.19(s,9H),1.15(s,9H). 13 C NMR (125MHz, CDCl3) δ178.22,176.46,167.30,135.11,132.77,129.14,128.49,126 .27,121.83,101.46,96.61,69.81,64.90,39.37,38.82,27.12,26.81.LRMS(ESI):C 23 H 29 NO6[M+H]+ measured value: 416.4.

[0280] Examples of the use of the oxazoline sugar of formula I of the present invention as a synthetic intermediate are as follows:

[0281]

[0282] The following is an example of preparing the compound of formula IV:

[0283] Example IV-1 Preparation of Compound IV-1

[0284]

[0285] Compound II-1 (39 mg, 0.1 mmol) was dissolved in acetone (5 ml). A 2M solution of hydrochloric acid in ether (100 μl, 0.2 mmol) was then added. After stirring, a drop of deionized water was added. After stirring at room temperature for two days, a large amount of precipitate formed. Filtration afforded a white solid, the hydrochloride salt of IV-1 (27.5 mg, 67% yield). 1 H NMR(400MHz, CDCl3)δ8.03(dd,J=8.3,1.4Hz,2H),7.65–7.56(m,1H),7.47(t, J=7.7Hz,2H),5.48(t,J=9.7Hz,1H),5.13(m,2H),4.36(d,J=8.7Hz,1H),4.29 (dd,J=12.3,4.9Hz,1H),4.17(dd,J=12.3,2.3Hz,1H),3.85–3.75(m,1H),2.1 4(d,J=1.0Hz,3H),2.07(d,J=0.9Hz,3H),1.95(d,J=0.9Hz,3H).HRMS(ESI):C 19 H 24 NO9[M+H] + Calculated value: 410.1446, measured value: 410.1441.

[0286] Example IV-2 Preparation of Compound IV-2

[0287]

[0288] II-1 (3 g, 7.67 mmol) was placed in a 100 ml round-bottom flask, 50 ml of methanol was added to dissolve it, and then triethylamine (5.3 ml, 5 eq) was added and stirred for 2 days. After TLC detection, the reaction mixture was dried to obtain 2.2 g of an oily product, which was then added to 30 ml of dry DMF for dissolution. Benzyl bromide (4.87 ml, 5 eq) and 60% NaH (1.60 g, 5 eq) were subsequently added. The mixture was reacted under nitrogen for 30 minutes. After TLC detection, the reaction mixture was quenched with deionized water (50 ml), extracted twice with ethyl acetate (50 ml), and the organic phases were combined and washed twice with water (50 ml), washed once with saturated sodium chloride (50 ml), dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. Dichloromethane was added to redissolve it and the sample was mixed with silica gel. After elution with flash column chromatography, a total of 2.53 g of a yellow solid product was obtained with a yield of 62%. 1H NMR(600MHz, CDCl3)δ7.97–7.95(m,1H),7.51(t,J=7.4Hz,1H),7.41(d,J=1.5Hz,2H),7.38–7.34(m,5H),7.33–7.29(m,5H),7.29–7.24(m,5H),7 .18–7.16(m,1H),6.09(d,J=7.6Hz,1H),4.85(d,J=11.8Hz,1H),4.77–4. 69(m,3H),4.67(dd,J=7.5,4.6Hz,1H),4.60(d,J=12.0Hz,1H),4.50(dd, J=11.7,7.1Hz,2H),3.89(dd,J=6.9,4.7Hz,1H),3.82(dd,J=8.9,6.9Hz,1H),3.72(d,J=2.9Hz,1H),3.63(d,J=9.0Hz,1H). 13 CNMR (150MHz, CDCl3) δ165.9,138.1,137.9,132.3,128.7,128.5,128.4,128.4,128.3,128.0,127.9, 127.9,127.9,127.7,127.6,126.9,94.1,81.2,80.2,74.6,73.8,73.5,72.7,71.8,69.4.HRMS (ESI): C 34 H 34 NO5[M+H] + Calculated value: 536.2431, measured value: 536.2438.

[0289] The above compound (1 g, 1.86 mmol) was placed in a 100 ml round-bottom flask and dissolved in 30 ml of acetone. A 2 M ethereal hydrochloric acid solution (1 ml) was then added, followed by 10 drops of purified water. After stirring at room temperature for one day, a large amount of precipitate formed. Filtration afforded a white solid, the hydrochloride salt of IV-2, totaling 0.857 g, for an 83% yield. 1H NMR (500MHz, DMSO-d6) δ9.06 (s, 2H), 8.01–7.95 (m, 2H), 7.71–7.65 (m, 1H), 7.54 (t, J = 7. 8Hz,2H),7.35(d,J=4.3Hz,4H),7.33–7.25(m,4H),7.20(dd,J=7.6,1.9Hz,2H),7.17–7.0 6(m,3H),7.04–6.95(m,2H),5.13(t,J=9.2Hz,1H),4.94(d,J=9.0Hz,1H),4.71(dd,J=11 .0,6.9Hz,2H),4.61–4.48(m,4H),4.04(t,J=9.2Hz,1H),3.90(m,1H),3.75–3.61(m,3H). 13 C NMR(125MHz,DMSO-d6)δ206.94,165.33,138.24,138.18,137.96,134.04,130.04,129.82,129.05,128.75,128.73,128.53,1 28.34,128.31,128.20,128.08,128.01,81.99,79.24,77.59,76.84,75.07,74.61,72.78,72.61,68.38,31.11.HRMS (ESI): C 34 H 36 NO6[M+H] + Calculated value: 554.2537, measured value: 554.2549.

[0290] Example IV-3 Preparation of Compound IV-3

[0291]

[0292] Compound II-8 (43.3 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask, dissolved in 30 ml of acetone, and then a 2 M hydrochloric acid ether solution (100 μl, 0.2 mmol) was added. Then, 1 drop of pure water was added. After stirring at room temperature for 1 day, a large amount of precipitate was precipitated. The white solid product was filtered off to obtain the hydrochloride salt of IV-3, a total of 10.1 mg, and the yield was 23%. 1H NMR(600MHz,MeOH-d4)δ8.12–8.00(m,4H),5.57(q,J=9.2Hz,1H),5.37–5.24(m,1H),5.18–5.11(m, 1H), 5.05 (dd, J=19.6, 9.0Hz, 1H), 4.33–4.24 (m, 1H), 4.20–4.12 (m, 2H), 2.58 (s, 3H), 1.99 (s, 9H). 13 C NMR(150MHz,MeOD4)δ198.08,170.63,169.87,169.68,164.87,140.98,132.16,129.94,129.59,12 8.14,126.41,79.31,74.51,71.91,71.21,67.30,61.22,25.64,19.18,19.09,18.96.HRMS (ESI): C 21 H 26 NO 10 [M+H] + Calculated value: 452.1551, measured value: 452.1555.

[0293] Example IV-4 Preparation of Compound IV-4

[0294]

[0295] Compound IV-2 (55.3 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask, dissolved in 5 ml of dichloromethane and 3 drops of triethylamine. Copper acetate (18.2 mg, 0.1 mmol) and p-methylphenylboronic acid (39 mg, 0.3 mmol) were then added to the reaction solution. The mixture was stirred at room temperature for 2 days. After TLC analysis, the reaction solution was quenched with water (30 ml) and extracted twice with ethyl acetate (15 ml). The combined organic phases were washed twice with water, dried over anhydrous sodium sulfate, and evaporated to dryness under reduced pressure. The product was separated by silica gel chromatography to obtain a white solid product (15.8 mg, 25% yield). 1H NMR (600 MHz, acetone-d6) δ 8.06 (dd, J = 8.4, 1.4 Hz, 2H), 7.66–7.61 (m, 1H), 7.50 (dd, J = 8.3, 7.4 Hz, 2H), 7.36–7.28 (m, 10H), 7.16 (m, 5H), 6.93–6.90 (m, 2H), 6.74–6.70 (m, 2H), 5.36 (d, J = 9.9 Hz ,1H),5.22(t,J=9.2Hz,1H),5.07(dd,J=9.9,9.0Hz,1H),4.91–4.86(m,2H),4.75(dd,J=27.2 ,11.1Hz,2H),4.62–4.53(m,2H),4.13(dd,J=9.3,8.6Hz,1H),3.84–3.78(m,3H),2.16(s,3H). 13 C NMR (150 MHz, acetone-d6) δ 165.32, 143.42, 138.31, 138.27, 138.07, 132.85, 129.10, 128.87, 128.13, 127.77, 127.70, 127.61, 127.39, 127.23, 127.22, 127.05, 126.93, 126.84, 113.94, 83.34, 83.28, 78.17, 75.29, 74.51, 74.07, 73.68, 72.44, 68.65, 19.14. HRMS (ESI): C 41 H 42 NO6[M+H] + Calculated value: 644.3007, measured value: 644.3010.

[0296] Example IV-5 Preparation of Compound IV-5

[0297]

[0298] IV-2 (55.3 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask, and 5 ml of tetrahydrofuran was added to dissolve it. Triethylamine (43.2 μl, 0.3 mmol) and succinic anhydride (15 mg, 0.15 mmol) were added to the reaction solution in sequence, and stirred at room temperature for 3 h. After TLC detection, the reaction solution was quenched by adding water (30 ml), and then extracted twice with ethyl acetate (15 ml). The organic phases were combined and washed twice with water, dried over anhydrous sodium sulfate, and then evaporated to dryness under reduced pressure. The product was then separated by silica gel chromatography to obtain a white solid product, a total of 60.3 mg, and a yield of 92%. 1H NMR (400MHz, CDCl3) δ8.04–7.94(m,2H),7.60(t,J=7.4Hz,1H),7.45(t,J=7.6Hz,2H ),7.39–7.29(m,8H),7.22–7.08(m,7H),6.74(d,J=9.1Hz,1H),5.29(t,J=9.3Hz,1H) ,5.18(t,J=9.2Hz,1H),4.81(dd,J=10.9,8.0Hz,2H),4.77–4.63(m,2H),4.52(dd,J =17.7,11.4Hz,2H),3.91(m,2H),3.78(s,1H),3.68–3.63(m,1H),2.61–2.31(m,4H). 13 C NMR (125MHz, CDCl3) δ172.24,166.81,137.63,133.63,129.81,128.53,128.38,128.27,128.02,127.86,127.81,127.77,127.71,82.99, 78.38,75.43,75.06,73.55,73.52,67.95,30.71,29.66.HRMS(ESI):C 38 H 39 NNaO9[M+Na] + Calculated value: 676.2517, measured value: 676.2520.

[0299] Example IV-6 Preparation of Compound IV-6

[0300]

[0301] IV-2 (55.3 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask, 5 ml of dichloromethane was added, and triethylamine (43.2 μl, 0.3 mmol), N-BOC-L-aspartic acid-1-methyl ester (36 mg, 0.15 mmol) and HATU (76 mg, 0.2 mmol) were added to the reaction solution in sequence. The mixture was stirred at room temperature for 6 h. After the reaction was completed by TLC, the reaction solution was quenched by adding water (30 ml), and then extracted twice with ethyl acetate (15 ml). The organic phases were combined and washed twice with water. After drying over anhydrous sodium sulfate, the organic phase was evaporated to dryness under reduced pressure and then separated by silica gel chromatography to obtain a white solid product, a total of 57.1 mg, with a yield of 73%. 1H NMR (500MHz, CDCl3) δ8.0–8.0(m,2H),7.6(ddt,J=8.7,7.1,1.3Hz,1H),7.5–7.4(m,2H),7.4–7.3(m,10H),7.2–7. 1(m,8H),6.7(d,J=9.2Hz,1H),5.7(d,J=8.9Hz,1H),5.3(t,J=9.3Hz,1H),5.2(t,J=9.3Hz,1H),4.9–4.8(m,2H),4 .7(d,J=11.1Hz,1H),4.7(s,1H),4.6(d,J=10.8Hz,1H),4.5(d,J=12.0Hz,1H),4.5–4.4(m,1H),3.9(dt,J=29.3,9 .1Hz,2H),3.8–3.8(m,2H),3.6–3.6(m,1H),3.3(s,3H),2.8–2.8(m,1H),2.7(dd,J=16.5,4.4Hz,1H),1.4(s,9H). 13 C NMR (125MHz, CDCl3) δ171.4,170.7,166.7,155.6,137.8,137.7,137.7,133.6,129.9,129.1,128.5,128.4,128.3,128.0,127. 9,127.9,127.8,127.8,83.0,80.0,78.3,77.5,76.7,75.5,75.1,73.6,73.6,68.0,52.1,50.8,49.8,37.8,28.3.HRMS (ESI): C 44 H 51 N2O 11 [M+H] + Calculated value: 783.3487, measured value: 783.3499.

[0302] The following is an example of preparing the compound of formula V:

[0303]

[0304] Example V-1 Preparation of Compound V-1

[0305]

[0306] Compound III-1 (33.1 mg, 0.1 mmol) was dissolved in a dry round-bottom flask containing 3 ml of dry dichloromethane. Boron trifluoride etherate (20 μl) was then added and the reaction was allowed to proceed under nitrogen for 12 hours. After completion, the reaction was quenched with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was evaporated to remove the solvent and then dissolved in dichloromethane. The product was separated by silica gel column chromatography (PE:EA = 2:1) to obtain a gray oily product (28 mg, 95% yield). 1 HNMR (400MHz, CDCl3) δ7.87(m,2H),7.60–7.52(m,1H),7.47(dd,J=8.4,7.0Hz,2H),7.23(d,J=7.4Hz,1H,NH),7.04(dd,J=10.3,1.6Hz,1H),6. 33(dd,J=10.3,2.8Hz,1H),5.91(dd,J=7.5,2.0Hz,1H),4.98(s,1H),4.42(dd,J=11.8,5.2Hz,1H),4.26(dd,J=11.8,4.3Hz,1H),2.10(s,3H). 13 C NMR (125MHz, CDCl3) δ190.86,170.66,167.53,148.37,133.02,132.41,128.70,127.70,127.40,78.74,73.28,64.65,20.77.HRMS(ESI):C 15 H 16 NO5[M+H] + Calculated value: 290.1023, measured value: 290.1027.

[0307] Example V-2 Preparation of Compound V-2

[0308]

[0309] Compound III-1 (33.1 mg, 0.1 mmol) was dissolved in a dry round-bottom flask containing 3 ml of dry dichloromethane. N-bromosuccinimide (NBS) (18 mg, 0.1 mmol) was then added and reacted under nitrogen for 12 hours. After completion, the reaction was quenched with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was evaporated to remove the solvent and then dissolved in dichloromethane. The product was separated by silica gel column chromatography (PE:EA = 2:1) to obtain 25.5 mg of the yellow oily product in a yield of 72%. 1 H NMR (500MHz, CDCl3) δ7.92–7.86(m,2H),7.62–7.57(m,1H),7.53–7.48(m,2H),7.45(d,J=1.8Hz,1H),7.26(d,J=7.7Hz,1 H,NH),6.04(dd,J=7.7,2.0Hz,1H),4.98(m,1H),4.43(dd,J=11.8,5.2Hz,1H),4.27(dd,J=11.8,4.8Hz,1H),2.14(s,3H). 13 C NMR (150MHz, CDCl3) δ185.04,170.53,167.36,148.52,132.73,132.61,128.79,127.42,120.57,79.25,74.03,64.18,20.77.HRMS(ESI):C 15 H 15 BrNO5[M+H] + Calculated value: 368.0128, measured value: 368.0117.

[0310] Example V-3 Preparation of Compound V-3

[0311]

[0312] Compound III-1 (33.1 mg, 0.1 mmol) was dissolved in a dry round-bottom flask containing 3 ml of dry dichloromethane. Iodine monochloride (1 ml, 10 eq) was then added and the reaction was allowed to proceed under nitrogen for 12 hours. After completion, the reaction was quenched with saturated sodium thiosulfate (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was evaporated to remove the solvent and then dissolved in dichloromethane. The mixture was separated by silica gel column chromatography (PE:EA = 2:1) to afford 28.1 mg of a yellow solid in a 68% yield. 1 H NMR(500MHz,CD2Cl2)δ7.92–7.85(m,2H),7.78(d,J=1.8Hz,1H),7.66–7.57(m,1H),7.56– 7.51(m,2H),7.31(d,J=7.5Hz,1H),6.06(dd,J=7.8,1.8Hz,1H),5.02(m,1H),2.12(s,3H). 13 C NMR (125MHz, CD2Cl2) δ185.95,170.33,166.99,156.77,132.96,132.44,128.73,127.30,97.66,78.20,75.50,64.01,20.48.HRMS(ESI):C 15 H 15 INNaO5[M+Na] + Calculated value: 437.9809, measured value: 437.9814.

[0313] Example V-4 Preparation of Compound V-4

[0314]

[0315] Compound III-22 (41.6 mg, 0.1 mmol) was dissolved in a dry round-bottom flask containing 3 ml of dry dichloromethane. Boron trifluoride etherate (20 μl) was then added and the reaction was allowed to proceed under nitrogen for 12 hours. After completion, the reaction was quenched with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The product was dried on a rotary evaporator and redissolved in dichloromethane. The sample was mixed with silica gel and separated by silica gel column chromatography using a PE:EA ratio of 2:1 to afford a yellow oily product (30.5 mg, 92% yield). 1HNMR (500MHz, CDCl3) δ7.90–7.83(m,2H),7.59–7.51(m,1H),7.46(dd,J=8.3,7.0Hz,2H),7.23(d,J=7.5Hz,1H),7.04(dd,J=10.3,1.6Hz,1H),6 .32(dd,J=10.3,2.8Hz,1H),5.90(dd,J=7.5,2.0Hz,1H),4.97(s,1H),4.46(dd,J=11.7,5.1Hz,1H),4.21(dd,J=11.7,4.9Hz,1H),1.20(s,9H). 13 C NMR (125MHz, CDCl3) δ190.93,178.07,167.52,148.65,133.10,132.35,128.68,127.42,127.39,78.72,73.40,64.28,27.11.LRMS(ESI):C 18 H 21 NO5[M+H]+ measured value: 332.4.

[0316] The following is an example of preparing the compound of formula VI:

[0317]

[0318] Example VI-1 Preparation of Compound VI-1

[0319]

[0320] Compound III-1 (66.2 mg, 0.2 mmol) was dissolved in 3 ml of pH 8 buffer, followed by the addition of (R)-methyl 2-acetamido-3-mercaptopropionate (17.2 mg, 0.1 mmol). The mixture was stirred for 12 hours. After completion of the reaction, it was diluted with deionized water (20 ml) and extracted twice with ethyl acetate (20 ml). The organic phases were combined and washed once with deionized water (30 ml) and once with saturated sodium chloride (30 ml), dried over anhydrous sodium sulfate, and filtered. The organic phase was evaporated to remove the solvent and then dissolved in dichloromethane. The product was separated by silica gel column chromatography (DCM:MeOH = 15:1) to obtain 31.6 mg of the yellow oily product in a yield of 68%. 1H NMR (500MHz, CDCl3) δ7.84–7.81(m,2H),7.56–7.51(m,1H),7.45(t,J=7.7Hz,2H),7. 27(d,1H),6.44(d,J=7.2Hz,1H),5.75(d,J=7.8Hz,1H),4.82(m,1H),4.50(dd,J=12.2 ,2.2Hz,1H),4.43–4.38(m,1H),4.14–4.09(m,1H),3.78(s,3H),3.29–3.09(m,4H),3 .01(dd,J=13.8,5.2Hz,1H),2.71(dd,J=14.6,12.3Hz,1H),2.11(s,3H),2.07(s,3H). 13 C NMR (125MHz, CDCl3) δ198.63,170.86,170.12,167.23,132.88,132.47,128.71,127.4 0,80.54,78.08,63.47,52.96,52.09,45.40,43.76,33.01,23.07,20.85.HRMS(ESI):C 21 H 27 N2O8S[M+H] + Calculated value: 467.1483, measured value: 467.1474.

[0321] Example VI-2 Preparation of Compound VI-2

[0322]

[0323] The experimental procedure was the same as VI-1, except that the thiol substrate was replaced with a custom pentapeptide. The reaction was monitored by mass spectrometry, and the molecular weight of compound VI-2 was clearly visible, ESI-MS: 953.5 [M+H] + , mass spectrum as Figure 3 shown.

[0324] Example VI-3 Preparation of Compound VI-3

[0325]

[0326] The experimental procedure was the same as VI-1, except that the thiol substrate was replaced with cysteine-growth hormone-releasing peptide. The reaction was monitored by mass spectrometry, and the molecular weight of compound VI-2 was clearly visible, ESI-MS: 1068.6 [M+H] + , mass spectrum as Figure 4 shown.

[0327] The following are examples of preparation of other compounds:

[0328] Example VII-1 Preparation of Compound VII-1

[0329]

[0330] Compound IV-2 (55.3 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask. Acetone (5 ml) and 10 drops of 12 M hydrochloric acid were then added sequentially. After the solution was stirred thoroughly, sodium nitrite (13 mg, 0.2 mmol) was added. The reaction was allowed to react overnight at room temperature. After TLC monitoring of the reaction, the reaction solution was quenched with water (30 ml), extracted twice with ethyl acetate (20 ml), and the combined organic phases were washed twice with water. After drying over anhydrous sodium sulfate, the organic phase was evaporated to dryness under reduced pressure and separated on a silica gel plate to yield 45.1 mg of the product as a white solid, with a yield of 81%. 1 H NMR (500MHz, CDCl3) δ8.13–8.01(m,2H),7.59(t,J=7.4Hz,1H),7.47(d,J=7.8Hz,2H ),7.40–7.29(m,11H),7.21–7.17(m,4H),5.58(t,J=3.3Hz,1H),5.16(dd,J=10.0,3 .5Hz,1H),4.90–4.82(m,3H),4.64(d,J=12.4Hz,1H),4.59–4.55(m,2H),4.27(t,J= 9.5Hz,1H),4.18(dt,J=10.2,3.5Hz,1H),3.76–3.70(m,3H),3.11(d,J=3.5Hz,1H). 13 CNMR(125MHz, CDCl3)δ138.13,138.01,137.82,133.25,129.88,129.82,128.46,128.42,128.41,128.32,128.00,12 7.95,127.91,127.79,127.76,127.65,90.64,79.69,78.14,75.56,75.12,74.20,73.54,70.43,68.78.HRMS (ESI): C 34 H 38 NO7[M+NH4] + Calculated value: 572.2643, measured value: 572.2628.

[0331] Example VII-2 Preparation of Compound VII-2

[0332]

[0333] Compound II-24 (55 mg, 0.1 mmol) was dissolved in 5 ml of DMF, and copper powder (64 mg, 1.0 mmol) was added. The mixture was stirred evenly and heated to 120°C for 4 h. The reaction solution was quenched with 20 ml of water and extracted twice with 15 ml of ethyl acetate. The combined organic phases were washed once with water and once with saturated sodium chloride, dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, and separated on a silica gel column to obtain 38.0 mg of a colorless oily product with a yield of 40%. 1 H NMR(500MHz, CDCl3)δ7.29(s,1H),5.79(d,J=7.6Hz,2H),4.93–4.85(m,4H),4.28(m,4H),4 .06(m,2H),3.98(s,12H),3.96(s,2H),3.73(s,6H),2.09(s,6H),2.08(s,6H),1.99(s,6H). 13 C NMR (125MHz, CDCl3) δ170.63,169.52,169.24,166.93,152.88,151.96,121.16,108.4 6,92.58,71.78,67.53,67.47,62.73,60.88,60.56,56.21,20.74,20.59.HRMS (ESI): C 44 H 53 N2O 22 [M+H] + Calculated value: 961.3084, measured value: 961.3092.

[0334] Example VII-3 Preparation of Compound VII-3

[0335]

[0336] Compound II-1 (1.5 g, 3.83 mmol) was placed in a 100 ml round-bottom flask, 50 ml of methanol was added to dissolve it, and then triethylamine (2.5 ml 5 eq) was added and stirred for 2 days. After TLC detection, the reaction of the raw material was complete, and the reaction solution was dried to obtain an oily product. 30 ml of dry acetonitrile was added to dissolve it, and then benzaldehyde (2 ml, 2 eq) and p-toluenesulfonic acid ((3.5 g, 2 eq)) were added in sequence. The reaction was carried out under nitrogen protection for 6 hours. After TLC detection, the reaction solution was diluted with deionized water (50 ml), extracted twice with ethyl acetate (50 ml), and the organic phases were combined and washed twice with water (50 ml), washed once with saturated sodium chloride (50 ml), dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, redissolved in dichloromethane and mixed with silica gel. The yellow oily product was separated by column chromatography, a total of 1.06 g, and a yield of 79%. 1 H NMR (600MHz, CDCl3) δ8.07–8.02(m,2H),7.47(dd,J=6.7,3.3Hz,4H),7.42–7.35(m,4H),6.05(d,J=8.0Hz,1H),5.60(d,J=6.7Hz,1H ),4.69(dd,J=8.0,5.7Hz,1H),4.46(dd,J=10.4,4.9Hz,1H),3.94(dd,J=9.6,5.7Hz,1H),3.82–3.70(m,2H),3.59(t,J=9.4Hz,1H). 13 C NMR (150MHz, CDCl3) δ164.35,136.47,131.98, 129.46,128.90,128.19,128.06,127.90,126.31,125.76,101.50,94.87,80.19,78.11,74.32,68.24,62.58,29.23.HRMS (ESI): C 20 H 20 Calculated for NO5[M+H]+: 354.1336, found: 354.1335.

[0337] Example VII-4 Preparation of Compound VII-4

[0338]

[0339] Compound VII-3 (45 mg, 1 mmol) was dissolved in 5 ml of dry DMF. Under nitrogen protection, benzyl bromide (30 μl, 2 eq) and NaH (12 mg, 2 eq) were added in sequence and stirred at room temperature for 30 minutes. After the reaction was completed by TLC monitoring, the reaction solution was quenched with deionized water (20 ml), extracted twice with ethyl acetate (20 ml), and the organic phases were combined, washed twice with water (2 ml), washed once with saturated sodium chloride (20 ml), dried over anhydrous sodium sulfate, evaporated to dryness under reduced pressure, redissolved in dichloromethane and mixed with silica gel. The yellow solid product was separated by column chromatography, a total of 42.1 mg, with a yield of 95%. 1 H NMR (500MHz, CDCl3) δ7.98–7.91(m,2H),7.59–7.52(m,1H),7.51–7.42(m,5H),7.42–7.27(m,7H),6.06(d,J=8.1Hz,1H),5 .64(s,1H),4.94–4.84(m,2H),4.77(dd,J=8.1,4.6Hz,1H),4.44(dd,J=10.6,5.2Hz,1H),3.86–3.73(m,3H),3.66(m,1H). 13 C NMR (125MHz, CDCl3) δ164.83,132.39,128.99,128.62,128.47,128.41,128.20,128.03, 127.82,126.07,101.34,95.35,80.74,80.62,78.85,73.20,68.83,62.85.HRMS(ESI):C 27 H 26 Calculated for NO5[M+H]+: 444.1805, found: 444.1815.

[0340] Example VII-5 Preparation of Compound VII-5

[0341]

[0342] Compound VII-4 (45 mg, 0.1 mmol) was placed in a 10 ml round-bottom flask and acetone (3 ml) was added to dissolve it. Subsequently, 2 M hydrochloric acid ether solution (0.25 ml) and water (25 μL) were added. After dissolution, the mixture was stirred at room temperature overnight. After the reaction was completed as monitored by TLC, the reaction solution was evaporated to dryness under reduced pressure. The residue was washed with dichloromethane three times and filtered to obtain 35.2 mg of a yellow solid product with a yield of 94%. 1H NMR(500MHz, DMSO-d6)δ8.97(s,2H),7.97(d,J=7.6Hz,2H),7.69(t,J=7.3Hz,1H),7.55(t,J=7.7Hz,2H),7.18–7.12(m,1H),7.12–7.03(m,4H), 5.80(s,1H),5.06(t,J=9.2Hz,1H),4.87(d,J=9.0Hz,1H),4.81(d,J=11 .5Hz,1H),4.56(d,J=11.5Hz,1H),3.83–3.74(m,2H),3.62–3.49(m,5H). 13 C NMR (125MHz, DMSO-d6) δ164.98,138.17,133.52,129.61,129.57,128.57,127.93,127.45,127.35,81.75,79.48,78.96, 73.98,71.90,69.53,60.01.HRMS(ESI):C 20 H 24 NO6[M+H] + , calculated value: 374.1598, measured value: 374.1596.

Claims

1. An oxazoline carbohydrate compound represented by formula I or a pharmaceutically acceptable salt thereof: in, is a double bond; n is 1; R 1 is one or two substituents on ring A selected from C1-C3 alkyl, benzyloxy C1-C3 alkyl, hydroxy C1-C3 alkyl, C1-C6 alkanoyloxy C1-C3 alkyl, C6-C12 aroyloxy C1-C3 alkyl, and hydrogen; R 2 Selected from naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the phenyl group are 1, 2, 3 or 4 substituents selected from C1-C6 alkyl, C1-C6 alkoxy, halogen, halogenated C1-C3 alkyl, C1-C6 alkanoyl, C2-C6 alkynyl, and phenyl; or, two adjacent substituents on the phenyl group together with the attached phenyl carbon atom form a 5-9 membered heterocyclic group, and the substituent of the 5-9 membered heteroaryl group is halogen; R 3 selected from hydrogen; R 4 Selected from hydroxyl, C1-C6 alkanoyloxy; Q is O; W is O.

2. The oxazoline carbohydrate compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein: R 2 Selected from naphthyl, substituted or unsubstituted phenyl, substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of the phenyl group are 1, 2, 3 or 4 substituents selected from C1-C3 alkyl, C1-C3 alkoxy, halogen, trifluoromethyl, C1-C3 alkanoyl, C2-C4 alkynyl, and phenyl, or two adjacent substituents on the phenyl group together with the connected phenyl carbon atom form a dioxolane, and the substituents of the 5-9 membered heteroaryl group are selected from F, Cl, Br, and I; R 4 Selected from C1-C6 alkanoyloxy; Q is O; W is O.

3. The oxazoline carbohydrate compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein: R 1 Selected from acetoxymethyl, valeryloxymethyl, benzoyloxymethyl, benzyloxymethyl, acetoxy, valeryloxy, benzoyloxy, methyl, ethyl, hydroxy, hydroxymethyl, monosaccharidyloxy, disaccharidyloxy, benzyloxy and hydrogen; R 2 is selected from methyl, ethyl, naphthyl, substituted or unsubstituted phenyl, and substituted or unsubstituted 5-9 membered heteroaryl, wherein the substituents of phenyl are 1, 2, 3 or 4 substituents selected from methyl, ethyl, methoxy, ethoxy, F, Cl, Br, I, trifluoromethyl, acetyl, ethynyl, and phenyl, and the 5-9 membered heteroaryl is selected from benzodioxolanyl, thienyl and furyl, and its substituents are selected from F, Cl, Br, I; R 3 selected from hydrogen; R 4 selected from acetyloxy, valeryloxy, benzoyloxy and benzyloxy; Q and W are O.

4. The oxazoline carbohydrate compound of formula I or a pharmaceutically acceptable salt thereof according to claim 1, wherein: The compound of formula I is the compound of formula III Among them, R 1 , R 2 , R 4 , W and Q are defined the same as in claim 1.

5. The compound shown below or a pharmaceutically acceptable salt thereof:

6. A method for preparing an oxazoline carbohydrate compound of formula I, comprising: Compound 1 and compound 2 are reacted in solvent S to generate a compound of formula I under the action of A. in, is a double bond or a single bond; n is 1; R 1 、R 2 、R 3 、R 4 , Q, W are respectively as defined in claim 1; R 5 and R 6 is selected from substituted or unsubstituted C1-C6 alkanoyl, substituted or unsubstituted C6-C12 aroyl, substituted or unsubstituted C6-C12 aryl or C1-C6 alkyl, wherein the substituents for substitution are selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; U is defined the same as W; wherein A is a Lewis acid, a protic acid, or a combination of a Lewis acid and a protic acid; The solvent S is an aprotic solvent, a protic solvent, or a combination of an aprotic solvent and a protic solvent.

7. The method according to claim 6, wherein: The method includes the following methods shown in route 2 and route 3: As shown in route 2, compound 1 and compound 2 are reacted in solvent S1 in the presence of A1 to generate compound II; As shown in Scheme 3, compound 1 and compound 2 are reacted in solvent S2 in the presence of A2 to generate compound III; Among them, n, R 1 , R 2 , R 3 , R 4 , W, Q, R 5 and R 6 The same definition as in claim 6; wherein A1 and A2 are Lewis acids, protic acids, or a combination of Lewis acids and protic acids; The solvents S1 and S2 are aprotic solvents, protic solvents, or a combination of aprotic solvents and protic solvents.

8. The use of the oxazoline carbohydrate compound represented by formula I for the specific modification of different sites on the sugar ring, for the flexible assembly of oligosaccharides and glycopeptides; and for the detection of sulfur-containing molecules and the specific modification of sulfhydryl groups of peptides or proteins. in, is a double bond or a single bond; n is 1; R 1 、R 2 、R 3 、R 4 , Q, and W are respectively as defined in claim 1.

9. The use according to claim 8, wherein The compound of formula I is a compound of formula II or III The use includes synthesizing the following compounds of formula IV, formula V or formula VI from compounds of formula II or formula III, including the following routes 4, 5 and 6: Compound II reacts with acid to generate 8 The compound IV is hydrogen, and then reacts with a carboxylic acid compound, anhydride, acyl chloride compound or halogenated compound to convert it into R 8 Compound IV which is not hydrogen; Among them, n, R 1 , R 2 , R 3 , W and Q are as defined in claim 8, R 8 is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, 2-(tert-butoxycarbonylamino) methyl pentanoate-4-carbonyl; In the method for synthesizing the compound of formula IV, the acid comprises a protic acid, a Lewis acid, or a combination thereof; Among them, R 1 , R 2 , R 4 , W and Q are as defined in claim 8, X is hydrogen or halogen; When X is hydrogen, compound V can be obtained by reacting compound III with water in the presence of an acid (Route 5); When X is a halogen, compound V can be obtained by reacting compound III with a halogenating agent (Route 5); Compound III reacts with a thiol-containing compound to convert into compound VI; Among them, R 1 , R 2 , R 4 , W and Q are as defined in claim 8, R 7 Selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, oligopeptide or polypeptide or protein containing cysteine ​​residue, wherein the substituent for substitution is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy.

10. The following compound prepared from the compound of formula I: in, is a double bond or a single bond; n is 1; R 1 、R 2 、R 3 、R 4 , Q, W are respectively as defined in claim 1; R 7 is selected from hydrogen, substituted or unsubstituted C1-C6 alkyl, substituted or unsubstituted C6-C12 aryl, oligopeptide or polypeptide or protein containing cysteine ​​residue, wherein the substituent for substitution is selected from halogen, C1-C6 alkyl, C1-C6 alkoxy; R 8 is hydrogen, p-tolyl, 1-carboxyethyl-4-carbonyl, p-methoxyphenylcarbonyl, 2-(tert-butoxycarbonylamino)pentanoic acid methyl ester-4-carbonyl, and X is hydrogen or halogen.

11. The compound according to claim 10, which is the following compound:

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