Indole glycoside compounds, pyrrole glycoside compounds, synthesis methods and applications

Abstract

The present invention relates to the technical fields of organic chemistry and medicinal chemistry, and specifically relates to indole glycoside compounds, pyrrole glycoside compounds, and synthesis methods and applications thereof. The specific technical solution is as follows: A nitroalkene sugar, a substituted indole or a substituted pyrrole, and a molecular sieve are stirred in an organic solvent for 6 to 12 hours to form a 1,3-bisindole-2-nitro sugar compound or a 1,3-bispyrrole-2-nitro sugar compound. The present invention solves the problems of lack of indole or pyrrole glycoside structural diversity, large-scale use of catalysts in the synthesis of corresponding glycosides, and poor glycoside selectivity in the prior art.

Description

Technical Field

[0001] The present invention relates to the technical fields of organic chemistry and medicinal chemistry, and particularly relates to an indole glycoside compound, a pyrrole glycoside compound, and a synthesis method and application thereof. Background Art

[0002] Indole compounds are widely present in natural products, active drugs, and pesticide molecules, and are also very important fine chemical raw materials. Therefore, the construction and modification of indole heterocycles have always been one of the research hotspots of synthetic chemists and medicinal chemists. Naturally occurring indole alkaloids exhibit different mechanisms and structures. The characteristics of bisindole alkaloids mainly lie in the two indole structures involved in the molecular structure, which can be indirectly connected through various structures, such as the anti-tumor drugs vinblastine and vincristine isolated from Catharanthus roseus. They can also directly polymerize to form natural bisindole alkaloids, such as staurosporine obtained from Streptomyces staurosporeus. Monomer dimerization has great potential in enhancing biological activity, reducing side effects, overcoming drug resistance, and changing pharmacokinetic, pharmacodynamic, or physicochemical characteristics.

[0003] On the other hand, in the 1990s, Swiss chemists first discovered the structure of indole C-glycoside Man(α1-C)Trp in the human body. Subsequently, the structures of such indole C-glycosides were successively discovered in glycoprotein biological macromolecules such as human serum sterilizing protein, erythropoietin receptor, and Ebola virus sGP protein. In vitro studies have shown that indole carbon glycoside compounds have excellent biological activities, including antiviral effects, inhibition of SGLT2, anti-inflammatory and analgesic effects, and anti-cancer and anti-tumor activities. Therefore, the research on indole carbon glycoside compounds has great development prospects.

[0004] The acquisition of early glycosides mainly relies on the extraction and separation of natural products. This method faces many problems such as long separation cycles, complex components, difficult separation, and high demand for raw materials. So far, the synthesis of indole carbosides can be classified into the following categories: a) Electron-rich aromatic compounds, such as indole reacting with activated glycosyl donors to form indole carbosides (Mandal, P., et al. J. Org. Chem 2021, 86, 8516–8526.); b) Transition metal-catalyzed reaction of terminal alkynyl sugars with o-iodoaniline or reaction of 1-iodoenol sugars with o-alkynylaniline to synthesize indole carbosides (Sun, J. S., et al. Org. Biomol. Chem. 2022, 18, 8834-8838.); c) Reaction of terminal halides with indole under the catalysis of organometallic reagents (Pd, Cu, Fe, Ni, etc.) to generate indole carbosides (Shevchenko, V. E., et al. Chem. Heterocycl. Compd. 1981, 17, 561-571. Subash, C. T., et al. Tetrahedron Lett. 2007, 48, 663-667. Deng, Z., et al. Nat. Catal. 2019, 2, 793–800.); d) Reaction of enol sugars with indole under the action of InCl3 to generate the corresponding indole carbosides (Yang, J. S., et al. Synthetic Comm. 2007, 37, 691-701. Kunwar, A. C., et al. Tetrahedron Lett. 2002, 43, 2095-2098.).

[0005] Most of the reported methods require pre-activation of glycosyl donors or indole; some have large leaving groups or directing groups (such as trichloroacetimidate, benzenethiol, etc.), with poor atom economy; or use precious metal / rare metal catalysts. These methods all have defects such as low selectivity, extremely difficult synthesis of ligands, or high catalyst prices. So far, there has been no report on the synthesis method and activity study of sugars substituted with bis-indole or bis-pyrrole at the 1,3-positions of the sugar ring. Summary of the Invention

[0006] Aiming at the deficiencies of the prior art, the present invention provides an indole glycoside compound and a pyrrole glycoside compound, their synthesis methods and applications, and solves the problems of lack of indole or pyrrole glycoside structural diversity, large use of catalysts in the synthesis of corresponding glycosides, and poor glycoside selectivity in the prior art.

[0007] To achieve the above objectives, the present invention is realized through the following technical solutions:

[0008] The present invention discloses an indole glycoside compound and a pyrrole glycoside compound, and the structural formula is shown as any one of the following formulas (Ⅰ):

[0009]

[0010] Among them, Pg 1 is any one of a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, and a silyl group; Pg 2 is any one of a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, and a silyl group; or, Pg 1 O and Pg 2 O are each independently substituted by any one of an azide group, a substituted amino group, a mercapto group, an alkyl thioether, and an aryl thioether;

[0011] R 1 and R 4 are each independently any one of a hydrogen atom, a methyl group, a benzyl group, an allyl group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, and an alkoxycarbonyl group; R 2 and R 3 are each independently any one of a hydrogen atom, a halogen, a methyl group, an alkyl group, a methoxy group, a methoxy group, a benzyloxy group, an aromatic ring, a heteroaromatic ring, an allyloxy group, a propargyloxy group, a nitro group, an ester group, a carbonyl group, a cyano group, an alkyl thioether group, an aryl thioether group, and a substituted amino group; R 5 and R 6 are each independently any one of a methyl group, an ethyl group, a tert-butyl group, and a phenyl group; Z is a carbon atom or a silicon atom.

[0012] Preferably, when Pg 1 and / or Pg 2 is any one of a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, and a silyl group, Pg 1 and / or Pg 2 can be respectively substituted by one or more independent R X ;

[0013] Or, when Pg 1 O and / or Pg 2 O is any one of a substituted amino group, a mercapto group, an alkyl thioether, and an aryl thioether, Pg 1 O and / or Pg 2 O can be respectively substituted by one or more independent R X ;

[0014] When R 1 and / or R 4 is any one of a methyl group, a benzyl group, an allyl group, an alkynyl group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, and an alkoxycarbonyl group, R 1 and / or R4 may be independently substituted by one or more respective Rs X substituted;

[0015] When R 2 and / or R 3 is any one of methyl, alkyl, methoxy, methoxy, benzyloxy, aromatic ring, heteroaromatic ring, allyloxy and propargyloxy, nitro, ester group, carbonyl group, cyano group, alkylthio group, arylthio group, and substituted amino group, R 2 and / or R 3 may be independently substituted by one or more respective Rs X substituted;

[0016] When R 5 and / or R 6 is any one of methyl, ethyl, tert-butyl, and phenyl, R 5 and / or R 6 may be independently substituted by one or more respective Rs x substituted;

[0017] The said R X is any one of a hydrogen atom, halogen, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide, hydroxyl, and sulfonamide.

[0018] Preferably, when R X is any one of alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide, hydroxyl, sulfonamide, R X may be substituted by one or more hydrogen atoms, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide, hydroxyl, sulfonamide.

[0019] Correspondingly, for the synthesis method of the above indole glycoside compounds and pyrrole glycoside compounds, nitroalkene sugar, the first molecule of substituted indole or substituted pyrrole, and molecular sieve are stirred in an organic solvent for 6 - 12 h to form 1,3-bisindole-2-nitro sugar compounds or 1,3-bispyrrole-2-nitro sugar compounds.

[0020] Preferably, the equivalent ratio of the nitroalkene sugar to the first molecule of substituted indole or substituted pyrrole is 1:1 - 10, the concentration of the organic solvent is 0.001 - 100 mol / L, the reaction temperature is -100 - 200 °C, and the concentration of the molecular sieve is 10 - 500 g / moL.

[0021] Preferably, the organic solvent is any one or a mixture of several solvents in any proportion selected from 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, chloroethanol, 2,2-dichloroethanol, dichloromethane, chloroform, acetonitrile, methanol, ethanol, tert-butanol, isopropanol, benzene, toluene, tetrahydrofuran, N,N-dimethylformamide, DMF, DMSO, 1,4-dioxane, 2-methyl-tetrahydrofuran, diethyl ether, tert-butyl methyl ether.

[0022] Preferably, a catalyst is added to the reaction system of nitroalkene sugar, substituted indole or substituted pyrrole. The dosage of the catalyst is 0.001 - 10.0 equivalents. The catalyst includes any one of BF3·Et2O, TMSOTf, TBSOTf, TESOTf, metal halides, metal sulfonates, perchloric acid and its metal salts, triarylboron, organic phosphoric acid, organic carbonyl acid.

[0023] Preferably, after adding the first molecule of substituted indole or substituted pyrrole and stirring the reaction until the nitroalkene sugar reaction is complete, the second molecule of substituted indole or pyrrole is added to the reaction system to form 1,3-bisindole-2-nitro sugar compounds or 1,3-bispyrrole-2-nitro sugar compounds. The indole or pyrrole at the 1-position and 3-position in the 1,3-bisindole-2-nitro sugar compounds or 1,3-bispyrrole-2-nitro sugar compounds is different. The equivalent of the second molecule of substituted indole or pyrrole is 1.0 - 10.0.

[0024] Correspondingly, a pharmaceutical composition includes the above-mentioned compound or the compound synthesized by the above-mentioned synthesis method, or its stereoisomer, tautomer or its salt, or its prodrug molecule, or a pharmaceutically acceptable carrier.

[0025] Correspondingly, the above-mentioned compound or the compound synthesized by the above-mentioned synthesis method, or its intermediate, or its stereoisomer, tautomer, or its salt, or its prodrug molecule is used in the preparation of drugs for treating Parkinson's disease, cancer or tumors.

[0026] The present invention has the following beneficial effects:

[0027] 1. The present invention adopts a one-step synthesis strategy, using 2-nitroalkene sugar and substituted indole (or pyrrole) as raw materials to efficiently and highly selectively synthesize a series of 1,3-bisindole (or pyrrole)-substituted glycoside compounds and 1-indole (or pyrrole)-2-nitroalkene sugar compounds. The whole synthesis process has the advantages of mild conditions, high yield, good selectivity and simple operation.

[0028] 2. The present invention can further efficiently and highly stereoselectively synthesize sugar derivatives with different indole or pyrrole substitutions at the 1-position and 3-position of the sugar ring by controlling the reaction temperature and the dosage of indole or pyrrole added.

[0029] 3. Since the protecting groups in the product can be removed under mild conditions, and the nitro groups in the product can be further converted into amino groups through simple reactions and further undergo other reactions, such as deamination to form 2-deoxy sugars, formation of amide bonds with carboxylic acids, and formation of amine derivatives through reductive amination; the nitro groups in the product can also be converted into ketone carbonyl groups through the Nef reaction and further reduced to hydroxyl groups, etc. The alpha position of the nitro group can also further react with other electrophilic reagents under basic conditions to form various sugar derivatives. Therefore, the present invention can provide an irreplaceable route for the diverse synthesis and modification of bis-indole and bis-pyrrole substituted sugar derivatives.

[0030] 4. Some of the 1,3-bis-indole (or pyrrole) substituted sugar derivatives obtained in the present invention exhibit good anti-Parkinson's disease biological activity and broad anti-tumor activity. BRIEF DESCRIPTION OF THE DRAWINGS

[0031] Figure 1 Cytotoxic activity diagrams of each compound against the following tumor cells and cancer cells (786-O human renal clear cell adenocarcinoma cells, MKN-45 human gastric cancer cells, A549 human lung cancer cells, HCT116 human colon cancer cells, 5637 human bladder cancer cells, GBC-SD human gallbladder cancer cells, HepG2 human liver cancer cells, DU145 human prostate cancer cells, MCF7 human breast cancer cells, A-673 human rhabdomyosarcoma cells, SF126 human brain tumor cells, CAL-62 human thyroid cancer cells, A-375 human malignant melanoma cells);

[0032] Figure 2 For each compound against MPP + Rescue activity, optimal activity concentration and effective duration diagrams of damaged SHSY5Y cells. DETAILED DESCRIPTION OF THE EMBODIMENTS

[0033] Next, the technical solutions in the embodiments of the present invention will be clearly and completely described in conjunction with the accompanying drawings in the embodiments of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without making creative efforts belong to the scope of protection of the present invention.

[0034] Unless otherwise specified, the technical means used in the implementation examples are conventional means well known to those skilled in the art.

[0035] 1. The present invention provides a 1,3-bis(indolyl) substituted sugar derivative and its synthesis method. The specific method is as follows: Nitroalkene sugar (1.0 equiv), substituted indole (1.0 - 10.0 equiv), molecular sieve (10 - 500 g / mol), and optionally a catalyst (0.001 equiv - 10.0 equiv) are added, and they are stirred in an organic solvent for 6 - 12 h within a certain temperature range to form a 1,3-bis(indolyl)-2-nitro sugar compound.

[0036] Among them, the nitroalkene sugar includes but is not limited to fully acetylated 2-nitroalkene sugars prepared from monosaccharides such as fully acetylated glucose 2-nitroalkene sugar, fully acetylated galactose 2-nitroalkene sugar, fully acetylated arabinose 2-nitroalkene sugar, fully acetylated rhamnose 2-nitroalkene sugar, etc.

[0037] The corresponding 2-nitroalkene sugars formed after functional group modification at the 6-position of the monosaccharide, fully acetylated 2-nitroalkene sugars of disaccharides, 2-nitroalkene sugars with different substitutions at the 4,6-positions. Among them, the 3-position substituent OPg includes but is not limited to protecting groups commonly used in carbohydrate chemistry such as acetoxy, benzyloxy, benzoyloxy, etc., and preferably acetyl. The 4-position Pg 1 , is any one of protecting groups commonly used in carbohydrate chemistry such as hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl, etc.; in particular, Pg 1 O can also be substituted by other functional groups such as azide, substituted amino, mercapto, alkylthioether, arylthioether, etc. The 6-position Pg 2 , is any one of protecting groups commonly used in carbohydrate chemistry such as hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl, etc.; in particular, Pg 1 O can also be substituted by other functional groups such as azide, substituted amino, mercapto, alkylthioether, arylthioether, etc.

[0038] Furthermore, the molecular sieve is (type A potassium), (type A sodium), (type A calcium), etc. molecular sieves widely used in organic synthesis reactions.

[0039] Furthermore, the catalyst is a Lewis acid catalyst, such as BF3·Et2O, TMSOTf, TBSOTf, TESOTf, metal halides (such as SnCl4, TiCl4, FeCl3, AlCl3, FeCl2, MgCl2, ZnCl2, ZrCl4, BiCl3, InCl3, FeBr3, FeBr2, BiBr3, InBr3, ZnBr2, MgBr2, ZnI2, MgI2, BiX3), metal sulfonates (such as Fe(OTf)2, Fe(OTf)3, In(OTf)3, Bi(OTf)3, Yb(OTf)3, Sc(OTf)3, Hf(OTf)4, etc.), perchloric acid and its metal salts (such as MgClO4, LiClO4, etc.), triarylboron (such as triphenylboron, etc.) or common hydrogen-bonding organic small molecule catalysts in organic synthetic chemistry (such as urea, substituted urea, thiourea, substituted thiourea), protonic acid catalysts (such as organic phosphoric acid, organic carbonyl acids [such as formic acid, acetic acid, trifluoroacetic acid, benzoic acid]).

[0040] Furthermore, the reaction concentration of the organic solvent is 0.001 - 100 mol / L, and the reaction temperature is -100 - 200 °C.

[0041] Furthermore, the organic solvent is any one of 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, chloroethanol, 2,2-dichloroethanol, dichloromethane (DCM), chloroform (CHCl3), acetonitrile (MeCN), methanol (MeOH), ethanol (EtOH), tert-butanol (t-BuOH), isopropanol (i-PrOH), benzene (PhH), toluene, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), dimethyl sulfoxide (DMSO), 1,4-dioxane, 2-methyl-tetrahydrofuran (2-MeTHF), ether, tert-butyl methyl ether or a mixture of any of these solvents in any proportion.

[0042] The reaction general formula is as follows:

[0043]

[0044] Among them, Pg is any one of hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl and other protecting groups commonly used in carbohydrate chemistry.

[0045] Pg 1 is any one of hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl and other protecting groups commonly used in carbohydrate chemistry.

[0046] Pg 2is any one of the protecting groups commonly used in carbohydrate chemistry, such as a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, etc.

[0047] R 1 is any one of a hydrogen atom, a methyl group, a benzyl group, an allyl group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group.

[0048] R 2 is any one of a hydrogen atom, a halogen, a methyl group, an alkyl group, a methoxy group, a methoxy group, a benzyloxy group, an aromatic ring, an aromatic heterocycle, an allyloxy group, a propargyloxy group, a nitro group, an ester group, a carbonyl group (including an aldehyde carbonyl and a ketone carbonyl), a cyano group, an alkylthio group, an arylthio group, a substituted amino group.

[0049] R 5 and R 6 are each any one of the protecting groups commonly used in carbohydrate chemistry to form a six-membered ring structure at positions 4 and 6 of the sugar ring, such as a methyl group, an ethyl group, a tert-butyl group, and a phenyl group, and Z is a carbon atom or a silicon atom.

[0050] Furthermore, when Pg and / or Pg 1 and / or Pg 2 is any one of a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, Pg and / or Pg 1 and / or Pg 2 can each be substituted by one or more independent R X groups.

[0051] Alternatively, Pg 1 O and Pg 2 O can each be substituted by other functional groups, such as an azide group, a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, etc. When Pg 1 O and / or Pg 2 O is any one of a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, Pg 1 O and / or Pg 2 O can each be substituted by one or more independent R X groups.

[0052] When R 1 is any one of a methyl group, a benzyl group, an allyl group, an alkyne group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group, R 1 can be substituted by one or more independent R X groups.

[0053] When R 2When R is any one of methyl, alkyl, methoxy, benzyloxy, aromatic ring, heteroaromatic ring, allyloxy, propargyloxy, nitro, ester group, carbonyl group (including aldehyde carbonyl and ketone carbonyl), cyano, alkylthio group, arylthio group, and substituted amino group, 2 it may be substituted by one or more R's X each being independent.

[0054] When R 5 and / or R 6 is any one of methyl, ethyl, tert-butyl and phenyl, R 5 and / or R 6 may be respectively substituted by one or more R's x each being independent.

[0055] Specifically: the said R X is any one of hydrogen atom, halogen, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl and sulfonamide.

[0056] Furthermore, when R X is any one of alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl, sulfonamide, R X may be substituted by one or more of hydrogen atom, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl, sulfonamide.

[0057] 2. The present invention provides a 1,3-bis(indole)-substituted sugar derivative and its synthesis method. The specific method is as follows: Nitroalkene sugar (1.0 equiv), the first molecule of substituted indole (1.0 - 5.0 equiv) and molecular sieve (10 - 500 g / mol) are stirred in an organic solvent (0.001 - 100 mol / L) within a certain temperature range (-100 - 200 °C) for 6 - 12 h. Subsequently, the second molecule of substituted indole (1.0 - 10.0 equiv) is added to form a 1,3-bis(different indole)-2-nitro sugar compound.

[0058] Among them, the selection of nitroalkene sugar, molecular sieve and organic solvent is the same as that in the above synthesis method 1.

[0059] The reaction general formula is as follows:

[0060]

[0061] Among them, Pg is any one of protecting groups commonly used in carbohydrate chemistry such as hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl, etc.

[0062] Pg 1 is any one of protecting groups commonly used in carbohydrate chemistry, such as hydrogen atom, methyl group, acetyl group, benzoyl group, benzyl group, allyl group, sulfonyl group, silyl group, etc.

[0063] Pg 2 is any one of protecting groups commonly used in carbohydrate chemistry, such as hydrogen atom, methyl group, acetyl group, benzoyl group, benzyl group, allyl group, sulfonyl group, silyl group, etc.

[0064] R 1 and R 4 are each independently any one of hydrogen atom, methyl group, benzyl group, allyl group, propargyl group, alkyl group, cycloalkyl group, sulfonyl group, acyl group, alkoxycarbonyl group.

[0065] R 2 and R 3 are each independently any one of hydrogen atom, halogen, methyl group, alkyl group, methoxy group, methoxy group, benzyloxy group, aromatic ring, heteroaromatic ring, allyloxy group, propargyloxy group, nitro group, ester group, carbonyl group (including aldehyde carbonyl, ketone carbonyl), cyano group, alkylthio group, arylthio group, substituted amino group.

[0066] R 5 and R 6 are each independently any one of methyl group, ethyl group, tert-butyl group and phenyl group, and Z is a carbon atom or a silicon atom.

[0067] Furthermore, when Pg and / or Pg 1 and / or Pg 2 is any one of methyl group, acetyl group, benzoyl group, benzyl group, allyl group, sulfonyl group, silyl group, Pg and / or Pg 1 and / or Pg 2 can be respectively substituted by one or more R X each independently.

[0068] Alternatively, Pg 1 O and Pg 2 O can be respectively substituted by any one of other functional groups such as azide group, substituted amino group, mercapto group, alkylthioether, arylthioether, etc. When Pg 1 O and / or Pg 2 O is any one of substituted amino group, mercapto group, alkylthioether, arylthioether, Pg 1 O and / or Pg 2 O can be respectively substituted by one or more R X each independently.

[0069] When R 1 and / or R 4When R is any one of methyl, benzyl, allyl, alkynyl, propargyl, alkyl, cycloalkyl, sulfonyl, acyl, alkoxycarbonyl, 1 and / or R 4 can each be substituted by one or more R X which are independent of each other.

[0070] When R 2 and / or R 3 is any one of methyl, alkyl, methoxy, methoxy, benzyloxy, aromatic ring, heteroaromatic ring, allyloxy, propargyloxy, nitro, ester group, carbonyl (including aldehyde carbonyl, ketone carbonyl), cyano, alkylthioether group, arylthioether group, substituted amino, R 2 and / or R 3 can each be substituted by one or more R X which are independent of each other.

[0071] Specifically: the said R X is any one of hydrogen atom, halogen, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxy and sulfonamide.

[0072] Furthermore, when R X is any one of alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxy, sulfonamide, R X is substituted by one or more of hydrogen atom, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxy, sulfonamide.

[0073] 3. The present invention provides a 1,3-bis(pyrrole)-substituted sugar derivative and its synthesis method. The specific method is as follows: nitrovinyl sugar (1.0 equiv), substituted pyrrole (1.0 - 10.0 equiv) and molecular sieve (10 - 500 g / mol) are stirred in an organic solvent (0.001 - 100 mol / L) within a certain temperature range (-100 - 200 °C) for 6 - 12 h to form a 1,3-bis(pyrrole)-2-nitro sugar compound.

[0074] Among them, the selection of nitrovinyl sugar, molecular sieve and organic solvent is the same as that in the above synthesis method 1.

[0075] The reaction general formula is as follows:

[0076]

[0077] Among them, Pg is any one of hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl and other protecting groups commonly used in carbohydrate chemistry.

[0078] Pg 1 is any one of protecting groups commonly used in carbohydrate chemistry, such as a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, etc.

[0079] Pg 2 is any one of protecting groups commonly used in carbohydrate chemistry, such as a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, etc.

[0080] R 1 is any one of a hydrogen atom, a methyl group, a benzyl group, an allyl group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group.

[0081] R 2 is any one of a hydrogen atom, a halogen, a methyl group, an alkyl group, a methoxy group, a methoxy group, a benzyloxy group, an aromatic ring, an aromatic heterocycle, an allyloxy group, a propargyloxy group, a nitro group, an ester group, a carbonyl group (including an aldehyde carbonyl group and a ketone carbonyl group), a cyano group, an alkylthio group, an arylthio group, a substituted amino group.

[0082] R 5 and R 6 are respectively any one of a methyl group, an ethyl group, a tert-butyl group and a phenyl group, and Z is a carbon atom or a silicon atom.

[0083] Further, when Pg and / or Pg 1 and / or Pg 2 is any one of a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, Pg and / or Pg 1 and / or Pg 2 can be respectively substituted by one or more independent R X groups.

[0084] Pg 1 O and Pg 2 O can be respectively substituted by other functional groups, such as any one of an azide group, a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, etc. When Pg 1 O and / or Pg 2 O is any one of a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, Pg 1 O and / or Pg 2 O can be respectively substituted by one or more independent R X groups.

[0085] When R 1 is any one of a methyl group, a benzyl group, an allyl group, an alkyne group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group, R 1 can be substituted by one or more independent R XSubstituted.

[0086] When R 2 is any one of methyl, alkyl, methoxy, methoxy, benzyloxy, aromatic ring, heteroaromatic ring, allyloxy, propargyloxy, nitro, ester group, carbonyl group (including aldehyde carbonyl, ketone carbonyl), cyano, alkylthio group, arylthio group, and substituted amino group, R 2 can be substituted by one or more R's each independently X Substituted.

[0087] Specifically: The said R X is any one of hydrogen atom, halogen, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl, and sulfonamide.

[0088] Furthermore, when R X is any one of alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl, sulfonamide, R X is substituted by one or more of hydrogen atom, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl, sulfonamide.

[0089] 4. The present invention provides a 1,3-bis(pyrrole)-substituted sugar derivative and its synthesis method. The specific method is as follows: Nitro-ene sugar (1.0 equiv), the first molecule of substituted pyrrole (1.0 - 5.0 equiv) and molecular sieve (10 - 500 g / mol) are stirred in an organic solvent (0.001 - 100 mol / L) within a certain temperature range (-100 - 200 °C) for 6 - 12 h. Subsequently, the second molecule of substituted pyrrole (1.0 - 10.0 equiv) is added to form a 1,3-bis(different pyrrole)-2-nitro sugar compound.

[0090] Among them, the selection of nitro-ene sugar, molecular sieve and organic solvent is the same as that in the above synthesis method 1.

[0091] The reaction general formula is as follows:

[0092]

[0093] Among them, Pg is any one of the protecting groups commonly used in carbohydrate chemistry such as hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl, etc.

[0094] Pg 1 is any one of the protecting groups commonly used in carbohydrate chemistry such as hydrogen atom, methyl, acetyl, benzoyl, benzyl, allyl, sulfonyl, silyl, etc.

[0095] Pg 2 is any one of protecting groups commonly used in carbohydrate chemistry, such as a hydrogen atom, a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, etc.

[0096] R 1 and R 4 are each independently any one of a hydrogen atom, a methyl group, a benzyl group, an allyl group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group.

[0097] R 2 and R 3 are each independently any one of a hydrogen atom, a halogen, a methyl group, an alkyl group, a methoxy group, a benzyloxy group, an aryl ring, an aromatic heterocycle, an allyloxy group, a propargyloxy group, a nitro group, an ester group, a carbonyl group (including an aldehyde carbonyl and a ketone carbonyl), a cyano group, an alkylthio group, an arylthio group, a substituted amino group.

[0098] R 5 and R 6 are each independently any one of a methyl group, an ethyl group, a tert-butyl group, and a phenyl group, and Z is a carbon atom or a silicon atom.

[0099] Furthermore, when Pg and / or Pg 1 and / or Pg 2 is any one of a methyl group, an acetyl group, a benzoyl group, a benzyl group, an allyl group, a sulfonyl group, a silyl group, Pg and / or Pg 1 and / or Pg 2 can be each independently substituted by one or more R X .

[0100] Alternatively, Pg 1 O and Pg 2 O can be each independently substituted by any one of other functional groups such as an azide group, a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, etc. When Pg 1 O and / or Pg 2 O is any one of a substituted amino group, a mercapto group, an alkylthio group, an arylthio group, Pg 1 O and / or Pg 2 O can be each independently substituted by one or more R X .

[0101] When R 1 and / or R 4 is any one of a methyl group, a benzyl group, an allyl group, an alkyne group, a propargyl group, an alkyl group, a cycloalkyl group, a sulfonyl group, an acyl group, an alkoxycarbonyl group, R 1 and / or R 4 can be each independently substituted by one or more R X .

[0102] When R 2 and / or R 3 is any one of methyl, alkyl, methoxy, methoxy, benzyloxy, aromatic ring, heteroaromatic ring, allyloxy and propargyloxy, nitro, ester group, carbonyl group (including aldehyde carbonyl and ketone carbonyl), cyano group, alkylthio group, arylthio group, and substituted amino group, R 2 and / or R 3 can be respectively substituted by one or more R X which are independent of each other.

[0103] Specifically: The said R X is any one of hydrogen atom, halogen, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl group and sulfonamide.

[0104] Furthermore, when R X is any one of alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl group, sulfonamide, R X is substituted by one or more hydrogen atoms, alkyl, fluoroalkyl, alkenyl, alkynyl, nitro, cyano, cycloalkyl, aryl, amino, alkoxy, substituted amino, amide group, hydroxyl group, sulfonamide.

[0105] In order to further elaborate on the synthesis of 1,3-bisindole (or pyrrole)-substituted glycoside compounds or 1-indole (or pyrrole)-2-nitroalkene sugar compounds in the present invention, the present invention selectively synthesized the following substances and elaborated on the synthesis process of each compound in combination with specific examples.

[0106]

[0107] Example 1 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W1)

[0108] The specific reaction process has the following 5 methods:

[0109] 1. Add (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS Molecular sieve (100 mg) and 0.4 mL of dry DCM (a dry solvent usually refers to a solvent with a water content ≤ 50 ppm) were slowly added dropwise with TMSOTf (54 μL, 0.3 mmol) at -20 °C. After the addition was completed, the reaction mixture was allowed to warm to room temperature naturally and react overnight. The reaction solution was concentrated under reduced pressure, and the crude product obtained was purified by silica gel column chromatography (the eluent was n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (17.3 mg, yield 16%).

[0110] The reaction equation is as follows:

[0111]

[0112] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0113] 1 H NMR (400 MHz, DMSO-d6) δ 7.97 (d, J = 7.8 Hz, 1H), 7.90 (s, 1H), 7.74 (d, J = 7.9 Hz, 1H), 7.55 (s, 1H), 7.48 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 7.9 Hz, 1H), 7.28–7.08 (m, 4H), 6.20 (d, J = 6.5 Hz, 1H), 6.10 (dd, J = 12.1, 6.5 Hz, 1H), 5.15 (t, J = 10.2 Hz, 1H), 4.50–4.40 (m, 1H), 4.16 (dd, J = 12.2, 5.5 Hz, 1H), 4.00–3.93 (m, 1H), 3.89 (s, 3H), 3.86 (m, 1H), 3.74 (s, 3H), 1.88 (s, 3H), 1.57 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 170.4, 169.2, 136.7, 136.5, 129.3, 128.1, 127.2, 122.4, 121.8, 119.9, 119.7, 119.2, 119.1, 111.1, 110.3, 110.1, 105.6, 86.5, 72.4, 70.2, 69.6, 62.8, 37.4, 33.1, 33.0, 20.9, 20.6; HRMS (ESI) calcd for C 28 H 29 N3NaO7 [M+Na] + 542.1898, found 542.1897.

[0114] 2. Add (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg), 1-[3,5-bis(trifluoromethyl)phenyl]-3-[(1S,2S)-(+)-2-(dimethylamino)cyclohexyl]thiourea (8.0 mg, 5 mol%), and 0.4 mL of dry DCM to a dry reaction tube, react at 65 °C for 12 - 24 h, concentrate the reaction solution under reduced pressure, and purify the obtained crude product by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (17.4 mg, yield 16%).

[0115] The reaction equation is as follows:

[0116]

[0117] 3. Add (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg), tris(pentafluorophenyl)borane (TPFPB, 5.1 mg, 5 mol%), and 0.4 mL of dry DCM to a dry reaction tube, react at 65 °C for 12 - 24 h, concentrate the reaction solution under reduced pressure, and purify the obtained crude product by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (17.6 mg, yield 17%).

[0118] The reaction equation is as follows:

[0119]

[0120] 4. Add (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS Molecular sieve (100 mg) and 0.4 mL of dry 1,1,1,3,3,3 - hexafluoroisopropanol (HFIP) were reacted at room temperature for 2 - 8 h. The reaction solution was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: n - hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2 - nitro - 1,3 - bis(1 - methyl - 3 - indolyl)-4 - acetoxy - 5 - acetoxymethylpyranose (51.9 mg, yield 50%).

[0121] The reaction equation is as follows:

[0122]

[0123] 5. (3S,4S,5R)-2 - nitro - 3,4 - diacetoxy - 5 - acetoxymethylpyran - 1 - ene (63.4 mg, 0.2 mmol), 1 - methylindole (57.6 mg, 0.44 mmol), MS were added to a dry reaction tube Molecular sieve (100 mg) and 0.4 mL of dry 2,2,2 - trifluoroethanol (TFE) were reacted at room temperature for 2 - 8 h. The reaction solution was concentrated under reduced pressure, and the obtained crude product was purified by silica gel column chromatography (eluent: n - hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2 - nitro - 1,3 - bis(1 - methyl - 3 - indolyl)-4 - acetoxy - 5 - acetoxymethylpyranose (93.4 mg, yield 90%).

[0124] The reaction equation is as follows:

[0125]

[0126] According to the above 5 synthesis methods, the yields of methods 1 - 4 are relatively low, and only the 5th synthesis method finally obtains a relatively high yield of the product. Therefore, all subsequent examples refer to the 5th synthesis method and no catalyst will be used anymore.

[0127] Example 2 Synthesis of (1R,2R,3R,4S,5R)-2 - nitro - 1,3 - bis((1 - methyl - 5 - bromo)-3 - indolyl)-4 - acetoxy - 5 - acetoxymethylpyranose (W2)

[0128] At room temperature, (3S,4S,5R)-2 - nitro - 3,4 - diacetoxy - 5 - acetoxymethylpyran - 1 - ene (63.4 mg, 0.2 mmol), 1 - methyl - 5 - bromoindole (92.0 mg, 0.44 mmol), MS were added to a reaction tube Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-bromo)-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (59.4 mg, yield 44%).

[0129] The reaction equation is as follows:

[0130]

[0131] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0132] 1 H NMR (400 MHz, DMSO-d6) δ 8.16 (s, 1H), 7.99 (s, 1H), 7.91 (s, 1H), 7.59 (s, 1H), 7.42 (d, J = 8.7 Hz, 1H), 7.33 (d, J = 8.7 Hz, 1H), 7.29 (d, J = 8.8 Hz, 1H), 7.24 (d, J = 8.8 Hz, 1H), 6.15 (d, J = 6.5 Hz, 1H), 6.04 (dd, J = 12.1, 6.6 Hz, 1H), 5.02 (t, J = 10.2 Hz, 1H), 4.38 (t, J = 11.3 Hz, 1H), 4.10 (dd, J = 12.2, 5.7 Hz, 1H), 3.88 (m, 1H), 3.84 (s, 3H), 3.80 (dd, J = 12.3, 2.7 Hz, 1H), 3.70 (s, 2H), 1.3 (s, 3H), 1.55 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 170.4, 169.1, 135.5, 135.3, 131.1, 129.8, 128.6, 124.9, 124.3, 122.2, 121.6, 112.9, 112.6, 112.3, 112.2, 111.2, 105.5, 86.1, 72.4, 70.2, 69.2, 62.7, 55.4, 40.9, 37.1, 33.4, 33.3, 20.9, 20.6; HRMS (ESI) calcd for C 28 H 27 Br2N3NaO7 [M + Na] + 698.0108, found 698.0108.

[0133] Synthesis of Example 3 (1R,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W3)

[0134] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyran-1-ene (63.4 mg, 0.2 mmol), 1-methyl-7-methoxy-indole (70.8 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (98.4 mg, yield 85%).

[0135] The reaction equation is as follows:

[0136]

[0137] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0138] 1 H NMR (600 MHz, CDCl3) δ 7.66 (t, J = 4.8 Hz, 2H), 7.32 (s, 1H), 6.91 (s, 1H), 6.85 - 6.83 (m, 2H), 6.77 (d, J = 2.2 Hz, 1H), 6.72 (d, J = 2.2 Hz, 1H), 6.17 (d, J = 6.2 Hz, 1H), 5.57 (dd, J = 12.5, 6.2 Hz, 1H), 5.21 (t, J = 10.2 Hz, 1H), 4.36 (dd, J = 12.4, 10.3 Hz, 1H), 4.17 (dd, J = 12.3, 5.6 Hz, 1H), 3.94 (dd, J = 12.3, 2.4 Hz, 1H), 3.88 (s, 3H), 3.87 (s, 3H), 3.76 (s, 3H), 3.66 (s, 3H), 1.97 (s, 3H), 1.63 (s, 3H); 1313C NMR (151 MHz, CDCl3) δ 170.7, 169.1, 157.1, 156.6, 137.6, 126.6, 124.3, 122.0, 120.7, 119.6, 110.8, 110.0, 109.6, 106.1, 92.8, 86.2, 72.2, 71.1, 69.8, 62.6, 55.7, 55.6, 37.7, 33.1, 32.9, 29.7, 20.8, 20.5; HRMS (ESI) calcd for C 30 H 34 N3O9 [M + H] + 580.2290, found 580.2283.

[0139] Example 4 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5,6-dimethoxy)-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (W4)

[0140] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethyl pyranose-1-ene (63.4 mg, 0.2 mmol), 1-methyl-5,6-dimethoxy-indole (84.0 mg, 0.44 mmol), MS molecular sieve (100 mg), and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5,6-dimethoxy)-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (113.7 mg, yield 89%).

[0141] The reaction equation is as follows:

[0142]

[0143] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0144] 11H NMR (600 MHz, CDCl3) δ 7.28 (s, 1H), 7.26 (s, 1H), 7.21 (s, 1H), 7.17 (s, 1H), 6.89 (s, 1H), 6.77 (s, 1H), 6.72 (s, 1H), 6.16 (d, J = 6.2 Hz, 1H), 5.54 (dd, J = 12.4, 6.3 Hz, 1H), 5.19 (t, J = 10.2 Hz, 1H), 4.34–4.27 (m, 1H), 4.15 (dd, J = 12.4, 5.2 Hz, 1H), 3.99 (s, 3H), 3.95 (s, 3H), 3.95 (s, 3H), 3.94 (s, 3H), 3.87 (m, 1H), 3.77 (s, 3H), 3.68 (s, 3H), 1.92 (s, 3H), 1.64 (s, 3H); 13 13C NMR (151 MHz, CDCl3) δ 170.7, 169.1, 147.7, 147.4, 145.4, 144.9, 131.6, 131.3, 125.9, 123.7, 120.4, 110.4, 105.6, 101.6, 101.3, 92.9, 92.7, 86.1, 72.2, 71.2, 69.9, 62.5, 56.9, 56.5, 56.3, 56.2, 37.8, 33.4, 33.1, 29.7, 20.7, 20.5; HRMS (ESI) calcd for C 32 H 38 N3O 11 [M+H] + 640.2501, found 640.2493.

[0145] Example 5 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-bromo-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W5)

[0146] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methyl-5-bromo-7-methoxyindole (105.1 mg, 0.44 mmol), MS Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-bromo-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (91.1 mg, yield 62%).

[0147] The reaction equation is as follows:

[0148]

[0149] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0150] 1 H NMR (400 MHz, DMSO-d6) δ 7.87 (s, 1H), 7.78 (d, J = 1.6 Hz, 1H), 7.52 - 7.47 (m, 2H), 6.83 (d, J = 1.6 Hz, 1H), 6.77 (d, J = 1.6 Hz, 1H), 6.10 (d, J = 6.6 Hz, 1H), 6.02 (dd, J = 12.0, 6.6 Hz, 1H), 5.02 (t, J = 10.2 Hz, 1H), 4.33 (t, J = 11.3 Hz, 1H), 4.15 (dd, J = 12.2, 5.5 Hz, 1H), 4.06 (s, 3H), 3.92 (s, 4H), 3.90 (s, 3H), 3.88 (s, 3H), 3.83 (dd, J = 12.2, 2.7 Hz, 1H), 1.89 (s, 3H), 1.62 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 170.4, 169.2, 148.5, 148.1, 131.5, 131.3, 129.2, 124.9, 115.2, 114.4, 112.8, 112.0, 106.8, 106.1, 105.6, 86.0, 70.1, 69.1, 62.7, 56.5, 56.3, 55.4, 36.9, 36.76, 20.9, 20.6; HRMS (ESI) calcd for C 30 H 31 Br2N3NaO9 [M + Na] + 758.0319, found 758.0301.

[0151] Synthesis of Example 6 (1R,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-5-propynyloxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W6)

[0152] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyran-1-ene (63.4 mg, 0.2 mmol), 1-methyl-5-propynyloxyindole (81.4 mg, 0.44 mmol), MS molecular sieve (100 mg), and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-propynyloxy)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (90.3 mg, yield 72%).

[0153] The reaction equation is as follows:

[0154]

[0155] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0156] 1 H NMR (400 MHz, CDCl3) δ 7.44 (s, 1H), 7.36 (t, J = 4.4 Hz, 2H), 7.21 (d, J = 8.8 Hz, 1H), 7.06–6.98 (m, 3H), 6.19 (d, J = 6.2 Hz, 1H), 5.58 (dd, J = 12.4, 6.2 Hz, 1H), 5.27 (t, J = 10.2 Hz, 1H), 4.82 (d, J = 2.4 Hz, 2H), 4.78 (d, J = 2.4 Hz, 2H), 4.36 (dd, J = 12.5, 10.4 Hz, 1H), 4.18 (dd, J = 12.3, 4.9 Hz, 1H), 4.00 (dd, J = 12.3, 2.4 Hz, 1H), 3.87 (m, 1H), 3.84 (s, 3H), 3.74 (s, 3H), 3.71 (d, J = 3.4 Hz, 1H), 2.57 (dt, J = 7.5, 2.4 Hz, 2H), 2.00 (s, 3H), 1.66 (s, 3H); 1313C NMR (101 MHz, CDCl3) δ 170.8, 169.1, 152.3, 151.9, 133.0, 132.6, 128.3, 128.1, 113.6, 112.4, 110.3, 105.6, 104.1, 103.8, 86.2, 79.4, 79.1, 75.4, 75.3, 71.9, 71.2, 69.8, 62.5, 57.3, 57.2, 56.8, 37.8, 33.4, 33.2, 29.7, 20.7, 20.5; HRMS (ESI) calcd for C 34 H 33 N3NaO9 [M+Na] + 650.2109, found 650.2114.

[0157] Example 7 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-allyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W7)

[0158] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-allylindole (69.1 mg, 0.44 mmol), MS molecular sieve (100 mg), and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1-allyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (66.2 mg, yield 58%).

[0159] The reaction equation is as follows:

[0160]

[0161] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0162] 11H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 6.9 Hz, 1H), 7.88 (s, 1H), 7.75 (d, J = 7.9 Hz, 1H), 7.57 (s, 1H), 7.46 (d, J = 8.2 Hz, 1H), 7.37 (d, J = 7.5 Hz, 1H), 7.24–7.18 (m, 1H), 7.17–7.09 (m, 3H), 6.20 (d, J = 6.5 Hz, 1H), 6.16–5.91 (m, 3H), 5.25–5.06 (m, 3H), 4.99–4.93 (m, 3H), 4.81–4.71 (m, 3H), 4.53–4.39 (m, 1H), 4.17 (dd, J = 12.1, 5.8 Hz, 1H), 4.04–3.96 (m, 1H), 3.91 (dd, J = 12.1, 2.7 Hz, 1H), 1.87 (s, 3H), 1.56 (s, 3H); 13 13C NMR (101 MHz, DMSO-d6) δ 170.4, 169.2, 136.2, 135.9, 134.9, 134.8, 128.5, 128.2, 128.1, 126.9, 122.4, 121.9, 120.1, 119.7, 119.4, 119.3, 116.9, 116.3, 111.2, 110.8, 110.5, 106.3, 86.7, 72.0, 70.6, 69.6, 62.9, 48.5, 48.3, 37.7, 20.9, 20.6; HRMS (ESI) calcd for C 32 H 34 N3O7 [M+H] + 572.23291, found 572.2400.

[0163] Example 8 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (W8)

[0164] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethyl pyranose-1-ene (63.4 mg, 0.2 mmol), indole (51.5 mg, 0.44 mmol), MS Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (54.0 mg, yield 55%).

[0165] The reaction equation is as follows:

[0166]

[0167] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0168] 1 H NMR (400 MHz, DMSO-d6) δ 11.40 (d, J = 2.6 Hz, 1H), 11.09 (d, J = 2.6 Hz, 1H), 7.83–7.77 (m, 2H), 7.63 (d, J = 7.8 Hz, 1H), 7.47 (d, J = 8.1 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.23–7.17 (m, 1H), 7.17–7.12 (m, 1H), 7.11–7.02 (m, 3H), 6.04 (d, J = 4.1 Hz, 1H), 5.99 (t, J = 10.2 Hz, 1H), 5.87 (s, 1H), 4.20–3.97 (m, 3H), 3.74 (m, 1H), 2.01 (s, 3H), 1.66 (s, 3H). 13 C NMR (101 MHz, DMSO) δ 170.5, 170.4, 137.1, 136.3, 127.1, 126.2, 124.7, 123.8, 122.5, 121.9, 120.4, 119.8, 119.4, 118.47, 109.2, 108.3, 88.9, 72.9, 71.1, 66.8, 63.5, 36.6, 21.1, 20.8. HRMS (ESI) calcd for C 26 H 25 N3NaO7 [M+Na] + 514.1585, found 514.1585.

[0169] Synthesis of Example 9 (1R,2R,3R,4S,5R)-2-nitro-1,3-bis((1,2,5-trimethyl)3-pyrrolyl)-4-acetoxy-5-acetoxymethyl pyranose (W9)

[0170] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), indole (48.0 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-1,3-bis(1,2,5-trimethyl)-3-pyrrolyl)-4-acetoxy-5-acetoxymethylpyranose (52.3 mg, yield 55%).

[0171] The reaction equation is as follows:

[0172]

[0173] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0174] 1 1H NMR (400 MHz, CDCl3) δ 6.15 (s, 1H), 5.70 (s, 1H), 5.59 (d, J = 6.7 Hz, 1H), 5.22 (dd, J = 12.0, 6.7 Hz, 1H), 5.09 (t, J = 10.3 Hz, 1H), 4.21 (dd, J = 12.3, 4.3 Hz, 1H), 4.10 - 4.06 (m, 1H), 4.00–3.88 (m, 2H), 3.34 (s, 3H), 3.29 (s, 3H), 2.21 (s, 6H), 2.14 (s, 3H), 2.10 (s, 3H), 2.06 (s, 3H), 1.87 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 170.9, 168.9, 129.2, 127.5, 127.2, 126.2, 113.0, 109.9, 105.8, 102.2, 87.4, 77.3, 71.1, 70.5, 69.5, 63.1, 37.7, 30.3, 30.1, 20.9, 20.7, 12.5, 10.2, 10.1; HRMS (ESI) calcd for C 24 H 34 N3O7 [M + H] + 476.2391, found 476.2385.

[0175] Synthesis of (1R,2R,3R,4S,5R)-2-Nitro-1,3-bis((1,5-dimethyl)-3-pyrrolyl)-4-acetoxy-5-acetoxymethylpyranose (W10) in Example 10

[0176] At room temperature, (3S,4S,5R)-2-Nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), indole (41.8 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain (1R,2R,3R,4S,5R)-2-Nitro-1,3-bis((1,5-dimethyl)-3-pyrrolyl)-4-acetoxy-5-acetoxymethylpyranose (78.1 mg, yield 87%).

[0177] The reaction equation is as follows:

[0178]

[0179] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0180] 1 H NMR (400 MHz, CDCl3) δ 6.41 (d, J = 3.7 Hz, 1H), 5.96 (d, J = 3.6 Hz, 1H), 5.85 (d, J = 3.7 Hz, 1H), 5.80 - 5.78 (m, 2H), 5.26 (dd, J = 12.2, 6.8 Hz, 1H), 5.07 (t, J = 10.2 Hz, 1H), 4.24–4.14 (m, 2H), 3.91 (dd, J = 12.4, 2.5 Hz, 1H), 3.77 - 3.73 (m, 1H), 3.62 (s, 3H), 3.51 (s, 3H), 2.21 (s, 3H), 2.19 (s, 3H), 2.05 (s, 3H), 1.84 (s, 3H); 13 C NMR (101 MHz, CDCl3) δ 170.6, 168.5, 131.8, 128.8, 128.3, 121.2, 109.7, 106.2, 105.8, 103.8, 85.3, 77.3, 72.8, 69.6, 69.4, 62.4, 37.7, 30.5, 30.1, 20.8, 20.4, 12.7, 12.5; HRMS (ESI) calcd for C 22 H 30 N3O7[M + H]+ 448.2078, found 448.2067.

[0181] Synthesis of Example 11 (1S,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-5-methoxy)3-indolyl)-4-acetoxy-5-p-toluenesulfonyloxymethylpyranose (W11)

[0182] At room temperature, (3R,4S,5R)-2-Nitro-3,4-diacetoxy-5-p-toluenesulfonyloxymethylpyranose-1-ene (85.8 mg, 0.2 mmol), 1-methyl-5-methoxyindole (70.8 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain ((1S,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-5-methoxy)3-indolyl)-4-acetoxy-5-p-toluenesulfonyloxymethylpyranose (89.8 mg, yield 65%).

[0183] The reaction equation is as follows:

[0184]

[0185] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0186] 1 H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 8.0 Hz, 2H), 7.46 (d, J = 7.8 Hz, 1H), 7.39–7.33 (m, 2H), 7.27 (dd, J = 5.7, 3.2 Hz, 2H), 7.22 (d, J = 8.0 Hz, 2H), 7.06 (s, 1H), 6.88 (dd, J = 8.9, 2.4 Hz, 1H), 6.79 (dd, J = 9.0, 2.3 Hz, 1H), 5.64 (dd, J = 11.6, 9.7 Hz, 1H), 5.35 (d, J = 9.6 Hz, 1H), 5.23 (s, 1H), 4.42–4.29 (m, 1H), 4.11 (d, J = 10.1 Hz, 2H), 3.82 (s, 3H), 3.79 (s, 2H), 3.74 (s, 3H), 3.69 (s, 3H), 2.31 (s, 3H), 1.55 (s, 3H); 1313C NMR (101 MHz, DMSO-d6) δ 169.1, 154.2, 153.9, 145.3, 132.5, 132.2, 130.4, 129.9, 128.1, 126.8, 112.0, 111.2, 111.1, 108.4, 76.7, 75.5, 69.3, 56.0, 33.1, 21.5, 20.7. HRMS (ESI) calcd for C 35 H 37 N3NaO 10 S [M+Na] + 714.2092, found 714.2090.

[0187] Example 12 Synthesis of (1S,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-4-acetoxy-5-azidomethylpyranose (W12)

[0188] At room temperature, (3R,4S,5R)-2-nitro-3,4-diacetoxy-5-azidomethylpyranose-1-ene (85.8 mg, 0.2 mmol), 1-methyl-5-propargyloxyindole (81.4 mg, 0.44 mmol), MS molecular sieve (100 mg), and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain ((1S,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-4-acetoxy-5-azidomethylpyranose (106.1 mg, yield 87%).

[0189] The reaction equation is as follows:

[0190]

[0191] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0192] 11H NMR (400 MHz, DMSO-d6) δ 7.53 (s, 1H), 7.45–7.38 (m, 2H), 7.36 (d, J = 8.9 Hz, 1H), 7.30 (d, J = 8.9 Hz, 1H), 7.18 (s, 1H), 6.96–6.81 (m, 2H), 5.66 (dd, J = 11.5, 9.6 Hz, 1H), 5.37 (d, J = 9.6 Hz, 1H), 5.25 (s, 1H), 4.87–4.73 (m, 4H), 4.24 (d, J = 8.6 Hz, 1H), 4.11 (s, 1H), 3.74 (s, 3H), 3.71 (s, 3H), 3.57 - 3.52 (m, 3H), 3.40 - 3.36 (m, 1H), 1.65 (s, 3H). 13 13C NMR (101 MHz, DMSO-d6) δ 169.3, 152.1, 152.1, 151.8, 133.0, 130.2, 126.6, 112.4, 111.2, 111.1, 108.7, 80.3, 80.3, 78.5, 78.3, 78.3, 56.9, 56.8, 51.2, 33.2, 33.1, 20.9. HRMS (ESI) calcd for C 32 H 30 N6NaO7 [M + Na] + 633.2068, found 633.2066.

[0193] Example 13 Synthesis of (1S,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-methoxy)3-indolyl)-4-acetoxy-5-tert-butyldimethylsilyloxymethyl pyranose (W13)

[0194] At room temperature, (3R,4S,5R)-2-nitro-3,4-diacetoxy-5-tert-butyldimethylsilyloxymethyl pyranose-1-ene (85.8 mg, 0.2 mmol), 1-methylindole (57.2 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain ((1S,2R,3R,4S,5R)-2-nitro-1,3-bis((1-methyl-5-methoxy)3-indolyl)-4-acetoxy-5-tert-butyldimethylsilyloxymethyl pyranose (63.8 mg, yield 54%).

[0195] The reaction equation is as follows:

[0196]

[0197] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0198] 1 H NMR(400MHz,CDCl3)δ7.86(dt,J=8.0,1.0Hz,1H),7.70(d,J=7.9Hz,1H),7.37–7.29(m,2H),7.28–7.22(m,2H),7.20(dt,J=7.0,1.4Hz,1H),7.18–7.12(m,1H),7.08(s,1H),7.05(s,1H),5.45(t,J=10.3Hz,1H),5.36–5.29(m,2H),4.15(t,J=10.4Hz,1H),4.00-3.95(m,1H),3.86(dd,J=11.4,2.8Hz,1H),3.80(dd,J=11.4,4.8Hz,1H),3.75(s,3H),3.74(s,3H),1.70(s,3H),0.92(s,9H),0.04(s,3H),0.00(s,3H). 13 C NMR(101MHz,CDCl3)δ169.1,137.3,136.9,127.5,126.8,126.0,122.3,121.9,120.2,119.8,119.3,118.8,109.5,109.5,109.4,108.3,91.3,81.4,77.2,70.7,63.1,43.7,32.9,29.7,25.9,20.6,18.3,-5.4.HRMS(ESI)calcd for C 32 H 41 N3NaO6Si[M+Na] + 614.2657,found 614.2657.

[0199] Synthesis of Example 14 (1S,2R,3R,4S)-2-nitro-1,3-bis((1-methyl)-3-indolyl)-4-acetoxypyranose (W14)

[0200] At room temperature, (3S,4S)-2-nitro-3,4-diacetoxypyranose-1-ene (49.0 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (the eluent was n-hexane / acetone = 8:1) to obtain (1S,2R,3R,4S)-2-nitro-1,3-bis((1-methyl)-3-indolyl)-4-acetoxypyranose (80.5 mg, yield 90%).

[0201] The reaction equation is as follows:

[0202]

[0203] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0204] 1 H NMR (400 MHz, DMSO-d6) δ 7.92 (s, 1H), 7.89 (d, J = 7.9 Hz, 1H), 7.58 (d, J = 8.0 Hz, 1H), 7.55 (s, 1H), 7.44 (dd, J = 8.3, 2.9 Hz, 2H), 7.25–7.17 (m, 2H), 7.14 (t, J = 7.4 Hz, 1H), 7.07 (t, J = 7.5 Hz, 1H), 5.70 (dd, J = 9.8, 5.7 Hz, 1H), 5.63 (d, J = 9.8 Hz, 1H), 5.05 (q, J = 2.2 Hz 1H), 4.50 (t, J = 4.5 Hz, 1H), 4.36 (d, J = 13.4 Hz, 1H), 3.91 (d, J = 13.3 Hz, 1H), 3.86 (s, 3H), 3.77 (s, 3H), 2.24 (s, 3H); 13 C NMR (101 MHz, DMSO-d6) δ 170.5, 137.1, 136.3, 129.1, 128.4, 126.7, 122.2, 122.1, 120.0, 119.7, 119.6, 118.4, 111.2, 110.5, 110.2, 106.6, 85.0, 71.4, 69.2, 65.5, 39.0, 33.1, 33.0, 21.6; HRMS (ESI) calcd for C 25 H 25 N3NaO5 [M+Na] + 470.1686, found 470.1687.

[0205] Synthesis of Example 15 (1S,2R,3R,4S,5S)-2-nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-4-acetoxypyranose (W15)

[0206] At room temperature, (3S,4S,5S)-2-nitro-3,4-diacetoxy-5-methylpyranose-1-ene (49.0 mg, 0.2 mmol), 1-methyl-5-methoxyindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1S,2R,3R,4S,5S)-2-nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-4-acetoxypyranose (80.5 mg, yield 90%).

[0207] The reaction equation is as follows:

[0208]

[0209] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0210] 1 H NMR (600 MHz, CDCl3) δ 7.65 (d, J = 8.7 Hz, 1H), 7.55 (d, J = 8.7 Hz, 1H), 6.99 (s, 1H), 6.92 (s, 1H), 6.87 (dd, J = 8.7, 2.2 Hz, 1H), 6.81 (dd, J = 8.7, 2.2 Hz, 1H), 6.73 (d, J = 2.2 Hz, 1H), 6.68 (d, J = 2.2 Hz, 1H), 5.31 (t, J = 10.6 Hz, 1H), 5.24 (d, J = 9.5 Hz, 1H), 5.16 (s, 1H), 4.04 (t, J = 11.2 Hz, 1H), 4.01–3.95 (m, 1H), 3.87 (s, 3H), 3.85 (s, 3H), 3.64 (s, 3H), 3.63 (s, 3H), 1.73 (s, 3H), 1.33 (d, J = 6.1 Hz, 3H). 13 C NMR (151 MHz, CDCl3) δ 169.6, 156.8, 156.5, 138.2, 137.7, 126.6, 120.3, 119.5, 110.0, 109.5, 109.4, 93.2, 92.8, 91.4, 77.0, 76.5, 55.7, 55.6, 43.7, 32.8, 20.6, 18.1. HRMS (ESI) calcd for C 28 H 31 N3NaO7 [M+Na] +544.2054, found 544.2049.

[0211] Synthesis of Example 16 (1S,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-lactose (W16)

[0212] At room temperature, (3R,4S,5R)-2-Nitro-lactose-1-ene (121.1 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at room temperature for 2 - 8 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 6:1) to obtain (1S,2R,3R,4S,5R)-2-Nitro-1,3-bis((1-methyl-5-methoxy)-3-indolyl)-lactose (101.7 mg, yield 62%).

[0213] The reaction equation is as follows:

[0214]

[0215] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0216] 1 H NMR (400 MHz, DMSO-d6) δ 7.93 (d, J = 7.8 Hz, 1H), 7.83 (s, 1H), 7.68 (d, J = 7.9 Hz, 1H), 7.51 (s, 1H), 7.48 (d, J = 8.2 Hz, 1H), 7.35 (d, J = 8.0 Hz, 1H), 7.22 (t, J = 7.6 Hz, 1H), 7.18–7.05 (m, 3H), 6.06 (d, J = 6.5 Hz, 1H), 5.80 (dd, J = 11.9, 6.5 Hz, 1H), 5.06 - 5.02 (m, 2H), 4.87 (d, J = 7.9 Hz, 1H), 4.67 (dd, J = 11.2, 7.6 Hz, 1H), 4.45 (t, J = 11.2 Hz, 1H), 4.21–4.09 (m, 3H), 3.97 (dt, J = 14.0, 5.4 Hz, 2H), 3.91 (s, 3H), 3.77 (s, 3H), 3.41 - 3.38 (m, 1H), 3.18 (dd, J = 11.1, 6.9 Hz, 1H), 1.97 (s, 3H), 1.89 (s, 3H), 1.83 (s, 3H), 1.57 (s, 3H), 1.50 (s, 3H); 1313C NMR(151MHz,DMSO-d6)δ170.6,170.2,170.1,170.0,169.4,136.9,136.5,129.4,128.3,128.1,122.4,121.4,120.1,119.9,119.1,118.8,111.5,110.3,109.8,105.6,98.1,88.5,78.5,70.9,70.7,69.5,69.3,68.9,67.2,63.4,60.7,37.1,33.2,32.9,30.0,21.0,20.7,20.7,20.2,20.1;HRMS(ESI)calcd for C 40 H 46 N3O 15 [M+H] + 808.2923,found 808.2904.

[0217] Example 17 Synthesis of (1S,2R,3R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-3-((1-methyl-5-bromo-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (W17)

[0218] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethyl pyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (27.5 mg, 0.21 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at -15 °C for 24 h. After the 2-nitro enose reaction was completed, 1-methyl-5-bromo-7-methoxyindole (71.7 mg, 0.3 mmol) was added, and the temperature was raised to 25 - 50 °C. The reaction was carried out for 2 - 6 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain ((1R,2R,3R,4S,5R)-2-nitro 1-((1-methyl)-3-indolyl)-3-((1-methyl-5-bromo-7-methoxy)-3-indolyl)-4-acetoxy-5-acetoxymethyl pyranose (72.7 mg, yield 58%).

[0219] The reaction equation is as follows:

[0220]

[0221] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0222] 1 1H NMR (600 MHz, DMSO-d6) δ 7.84 (d, J = 7.9 Hz, 1H), 7.52 (s, 1H), 7.49–7.39 (m, 2H), 7.40 - 7.32 (m, 1H), 7.20 (ddd, J = 8.2, 7.0, 1.2 Hz, 1H), 7.11 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 6.75 (d, J = 1.7 Hz, 1H), 5.67 (t, J = 10.6 Hz, 1H), 5.37 (d, J = 9.5 Hz, 1H), 5.19 (s, 1H), 4.31 (s, 1H), 4.20 (s, 1H), 4.14–4.04 (m, 2H), 3.91 (s, 3H), 3.87 (s, 3H), 3.76 (s, 3H), 1.98 (s, 3H), 1.64 (s, 3H). 13 13C NMR (151 MHz, DMSO-d6) δ 170.5, 169.4, 148.3, 137.2, 129.5, 126.4, 122.1, 120.1, 119.8, 112.2, 110.5, 109.1, 106.2, 90.1, 77.4, 75.5, 63.3, 56.4, 36.7, 33.0, 21.0, 20.7. HRMS (ESI) calcd for C 29 H 30 BrN3NaO8 [M + Na] + 650.1108, found 650.1107.

[0223] Example 18 Synthesis of (1S,2R,3R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-)-4-acetoxy-5-acetoxymethylpyranose (W18)

[0224] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyran-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (27.5 mg, 0.21 mmol), MS Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at -15 °C for 24 h. After the reaction of 2-nitroenoxysugar was completed, 5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinoline (47.1 mg, 0.3 mmol) was added, and the temperature was raised to 25 - 50 °C for reaction for 2 - 6 h. The reaction solution was concentrated and purified by silica gel column chromatography (the eluent was n-hexane / acetone = 8:1) to obtain (1S,2R,3R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-3-(5,6-dihydro-4H-pyrrolo[3,2,1-ij]quinolin-1-yl)-4-acetoxy-5-acetoxymethylpyranose (72.7 mg, yield 58%).

[0225] The reaction equation is as follows:

[0226]

[0227] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0228] 1 H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 7.9 Hz, 1H), 7.56–7.35 (m, 4H), 7.20 (t, J = 7.6 Hz, 1H), 7.12 (t, J = 7.5 Hz, 1H), 6.95 (t, J = 7.5 Hz, 1H), 6.83 (d, J = 7.0 Hz, 1H), 5.68 (t, J = 10.6 Hz, 1H), 5.40 (d, J = 9.7 Hz, 1H), 5.31 (t, J = 9.5 Hz, 1H), 4.33 - 4.28 (m, 1H), 4.16 - 4.08 (m, 5H), 3.76 (s, 3H), 2.89 (t, J = 6.2 Hz, 2H), 2.09 (q, J = 5.9 Hz, 2H), 1.98 (s, 3H), 1.67 (s, 3H). 13 C NMR (151 MHz, DMSO) δ 170.6, 169.4, 137.2, 134.2, 129.5, 126.4, 122.3, 122.1, 120.0, 119.9, 119.8, 118.7, 116.5, 110.5, 109.2, 90.5, 77.6, 75.5, 63.5, 55.4, 43.9, 33.0, 24.4, 22.7, 21.1, 20.8. HRMS (ESI) calcd for C 30 H 31 N3NaO7 [M+Na] + 568.2054, found 568.2060.

[0229] Synthesis of Example 19 (1S,2R,3R,4S,5S)-2-Nitro-1-((1-Methyl)-3-indolyl)-3-((1-Methyl-5-methoxy)3-indolyl)-4-acetoxypyranose (W19)

[0230] At room temperature, (3S,4S,5S)-2-Nitro-3,4-diacetoxy-5-methylpyranose-1-ene (49.0 mg, 0.2 mmol), 1-Methylindole (27.5 mg, 0.21 mmol), MS molecular sieve (100 mg) and 2,2,2-Trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at -15 °C for 24 h. After the 2-nitroenopyranose reaction was completed, 1-Methyl-5-methoxyindole (55.5 mg, 0.3 mmol) was added, and the temperature was raised to 25 - 50 °C. The reaction was carried out for 2 - 6 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-Hexane / Acetone = 8:1) to obtain (1S,2R,3R,4S,5S)-2-Nitro-1-((1-Methyl)-3-indolyl)-3-((1-Methyl-5-methoxy)3-indolyl)-4-acetoxypyranose (56.6 mg, yield 55%).

[0231] The reaction equation is as follows:

[0232]

[0233] The obtained product was measured on a nuclear magnetic resonance instrument, and the obtained nuclear magnetic resonance data were as follows:

[0234] 1 H NMR (400 MHz, DMSO-d6) δ 7.84 (d, J = 7.9 Hz, 1H), 7.58 - 7.48 (m, 1H), 7.49 – 7.40 (m, 2H), 7.30 (d, J = 8.8 Hz, 1H), 7.20 (m, 2H), 7.11 (td, J = 7.4, 6.9, 1.0 Hz, 1H), 6.85 (dd, J = 8.9, 2.4 Hz, 1H), 5.66 (dd, J = 11.5, 9.6 Hz, 1H), 5.33 (d, J = 9.6 Hz, 1H), 5.05 (s, 1H), 4.82 – 4.78 (m, 2H), 4.09 (m, 2H), 3.77 (s, 3H), 3.70 (s, 3H), 3.54 (t, J = 2.3 Hz, 1H), 1.67 (s, 3H), 1.16 (d, J = 6.1 Hz, 3H). 1313C NMR (101 MHz, DMSO) δ 169.3, 151.8, 137.1, 129.5, 126.4, 122.1, 119.8, 111.0, 110.5, 109.5, 90.9, 80.3, 78.3, 76.1, 75.5, 56.8, 33.2, 33.0, 20.9, 18.3. HRMS (ESI) calcd for C 29 H 30 N3O6 [M + H] + 516.2129, found 516.2131.

[0235] Example 20 Synthesis of (1S,2R,3R,4S,5R)-2-Nitro-1-((1-Methyl)-3-indolyl)-3-((1-propynyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W20)

[0236] At room temperature, (3S,4S,5R)-2-Nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-Methylindole (27.5 mg, 0.21 mmol), MS molecular sieve (100 mg), and 2,2,2-Trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at -15 °C for 24 h. After the 2-nitroenoxysugar reaction was complete, 1-Propynylindole (46.5 mg, 0.3 mmol) was added, and the temperature was raised to 25 - 50 °C. The reaction was carried out for 2 - 6 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-Hexane / Acetone = 8:1) to obtain (1S,2R,3R,4S,5R)-2-Nitro-1-((1-Methyl)-3-indolyl)-3-((1-propynyl)-3-indolyl)-4-acetoxy-5-methylpyranose (63.0 mg, yield 58%).

[0237] The reaction equation is as follows:

[0238]

[0239] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were:

[0240] 11H NMR (400 MHz, DMSO-d6) δ 7.87 (d, J = 7.9 Hz, 1H), 7.65 (d, J = 25.9 Hz, 2H), 7.52–7.41 (m, 3H), 7.26–7.05 (m, 4H), 5.74 (t, J = 10.6 Hz, 1H), 5.42 (d, J = 9.7 Hz, 1H), 5.32 (s, 1H), 5.05 (d, J = 2.5 Hz, 2H), 4.33 (dt, J = 9.3, 3.8 Hz, 1H), 4.21 (s, 1H), 4.11 (d, J = 4.3 Hz, 2H), 3.78 (s, 3H), 3.40 (d, J = 3.1 Hz, 1H), 1.99 (s, 3H), 1.62 (s, 3H). 13 13C NMR (101 MHz, DMSO) δ 170.6, 169.4, 137.2, 129.6, 126.4, 122.2, 122.1, 120.1, 119.9, 119.9, 110.7, 110.5, 109.2, 90.2, 79.4, 77.5, 76.2, 75.5, 63.4, 35.7, 33.0, 21.1, 20.7. HRMS (ESI) calcd for C 30 H 29 N3NaO7 [M+Na] + 566.1898, found 566.1903.

[0241] Example 21 Synthesis of (1S,2R,3R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-3-((1-methyl)-2-pyrrolyl)-4-acetoxy-5-acetoxymethylpyranose (W21)

[0242] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (27.5 mg, 0.21 mmol), MS molecular sieve (100 mg), and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at -15 °C for 24 h. After the 2-nitroenoxysugar reaction was complete, 1-methylpyrrole (24.0 mg, 0.3 mmol) was added, and the temperature was raised to 25 - 50 °C. The reaction was carried out for 2 - 6 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1S,2R,3R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-3-((1-methyl)-2-pyrrolyl)-4-acetoxy-5-acetoxymethylpyranose (45.0 mg, yield 48%).

[0243] The reaction equation is as follows:

[0244]

[0245] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were as follows:

[0246] 1 H NMR(400MHz,DMSO-d6)δ7.81(d,J=7.9Hz,1H),7.50–7.40(m,2H),7.20(t,J=7.6Hz,1H),7.10(t,J=7.5Hz,1H),6.60(t,J=2.2Hz,1H),6.30(s,1H),5.91(t,J=3.1Hz,1H),5.51(t,J=10.4Hz,1H),5.38(d,J=9.6Hz,1H),5.12(t,J=10.2Hz,1H),4.28(dt,J=9.3,4.4Hz,1H),4.18–4.02(m,3H),3.77(s,3H),3.55(d,J=16.7Hz,3H),1.98(s,3H),1.86(s,3H). 13 C NMR(101MHz,DMSO)δ170.6,169.2,137.1,129.6,127.1,126.4,123.2,122.1,119.9,119.9,110.5,109.0,107.4,107.1,90.3,77.4,75.4,63.4,42.6,33.6,33.0,21.1,20.7.HRMS(ESI)calcd for C 24 H 27 N3NaO7[M+Na] + 492.1741,found 492.1740.

[0247] Synthesis of Example 22 (1S,2R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-p-toluenesulfonyloxymethylpyran-2-ene (W22)

[0248] At room temperature, (3R,4S,5R)-2-nitro-3,4-diacetoxy-5-p-toluenesulfonyloxymethylpyran-1-ene (85.8 mg, 0.2 mmol), 1-methylindole (28.8 mg, 0.22 mmol), and MS were added to a reaction tube Molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were reacted and stirred at -15 °C for 24 - 48 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1S,2R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-p-toluenesulfonyloxymethylpyran-2-ene (68.0 mg, yield 68%).

[0249] The reaction equation is as follows:

[0250]

[0251] The obtained product was measured on a nuclear magnetic resonance spectrometer, and the nuclear magnetic resonance data obtained were as follows:

[0252] 1 H NMR (400 MHz, DMSO-d6) δ 7.67 (d, J = 8.3 Hz, 2H), 7.48 (d, J = 8.0 Hz, 1H), 7.45 (t, J = 4.1 Hz, 2H), 7.26–7.15 (m, 4H), 7.07 (ddd, J = 8.0, 7.0, 1.0 Hz, 1H), 6.09 (dd, J = 3.2, 2.2 Hz, 1H), 5.57 (ddd, J = 8.9, 3.3, 1.9 Hz, 1H), 4.30–4.05 (m, 3H), 3.77 (s, 3H), 2.30 (s, 3H), 2.04 (s, 3H). 13 C NMR (101 MHz, DMSO) δ 170.0, 151.6, 145.4, 137.1, 132.2, 130.8, 130.7, 130.4, 128.1, 126.2, 122.1, 120.0, 119.2, 110.6, 109.0, 73.1, 69.6, 68.8, 64.0, 33.0, 21.5, 21.1. HRMS (ESI) calcd for C 24 H 25 N2O8S [M + H] + 501.1326, found 501.1334.

[0253] Synthesis of Example 23 (1R,2R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyran-2-ene (W23)

[0254] At room temperature, (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (28.8 mg, 0.22 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction tube. The reaction was stirred at -15 °C for 24 - 48 h. The reaction solution was concentrated and purified by silica gel column chromatography (the eluent was n-hexane / acetone = 8:1) to obtain (1R,2R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose-2-ene (34.9 mg, yield 45%).

[0255] The reaction equation is as follows:

[0256]

[0257] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were:

[0258] 1 H NMR (400 MHz, DMSO-d6) δ 7.72 (dt, J = 7.9, 1.0 Hz, 1H), 7.49–7.43 (m, 2H), 7.33 (s, 1H), 7.25 - 7.21 (m, 1H), 7.15 - 7.11 (m, 1H), 6.26 (s, 1H), 5.60 (ddd, J = 8.9, 2.7, 1.8 Hz, 1H), 4.15 (dd, J = 12.3, 5.5 Hz, 1H), 3.93 (dd, J = 12.3, 2.8 Hz, 1H), 3.83 - 3.79 (m, 1H), 3.78 (s, 3H), 2.12 (s, 3H), 1.84 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 170.4, 170.3, 151.2, 137.5, 132.1, 129.9, 126.9, 122.5, 120.0, 119.4, 110.6, 109.5, 66.9, 66.4, 64.7, 62.6, 33.0, 21.2, 20.9. HRMS (ESI) calcd for C 19 H 20 N2NaO7 [M + Na] + 411.1163, found 411.1175.

[0259] Synthesis of Example 24 (1S,2R,4S,5R)-2-Nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyran-2-ene (W24)

[0260] At room temperature, (3R,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyran-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (28.8 mg, 0.22 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube. The reaction was stirred at -15 °C for 24 - 48 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1S,2R,4S,5R)-2-nitro-1-((1-methyl)-3-indolyl)-4-acetoxy-5-acetoxymethylpyran-2-ene (65.2 mg, yield 78%).

[0261] The reaction equation is as follows:

[0262]

[0263] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were:

[0264] 1 H NMR (400 MHz, DMSO-d6) δ 7.41 (s, 1H), 7.33 (d, J = 8.9 Hz, 1H), 7.27 (t, J = 2.1 Hz, 1H), 7.00 (d, J = 2.4 Hz, 1H), 6.83 (dd, J = 8.9, 2.4 Hz, 1H), 6.14 (t, J = 2.7 Hz, 1H), 5.66 (dt, J = 8.5, 2.6 Hz, 1H), 4.29–4.07 (m, 3H), 3.77 (s, 3H), 3.72 (s, 3H), 2.13 (s, 3H), 2.00 (s, 3H). 13 C NMR (101 MHz, DMSO-d6) δ 170.6, 170.2, 154.1, 151.7, 132.4, 131.0, 130.9, 126.7, 111.7, 111.4, 108.8, 101.4, 73.5, 69.5, 64.5, 62.9, 55.9, 33.1, 21.2, 21.0. HRMS (ESI) calcd for C 20 H 22 N2NaO8 [M+Na] + 441.1268, found 441.1274.

[0265] Synthesis of Example 25 (1S,2R,3R,4S,5R)-2-Nitro-1,3-bis(1-methyl-3-indolyl)-4-hydroxy-5-hydroxymethylenepyranose (W25)

[0266] At room temperature, (3S,4S,5R)-2-Nitro-3,4-diacetoxy-5-acetoxymethylenepyranose-1-ene (63.4 mg, 0.2 mmol), 1-methylindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-trifluoroethanol (0.4 mL) were added to a reaction test tube and reacted at room temperature for 2 - 8 h. After the reaction was completed, it was concentrated; then potassium carbonate (13.8 mg, 0.1 mmol) and 0.4 mL of MeOH were added, and stirred for 2 h. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: dichloromethane / methanol = 10:1) to obtain (1S,2R,3R,4S,5R)-2-Nitro-1,3-bis(1-methyl-3-indolyl)-4-hydroxy-5-hydroxymethylenepyranose (62.6 mg, yield 72%).

[0267] The reaction equation is as follows:

[0268]

[0269] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were:

[0270] 1 H NMR (400 MHz, DMSO-d6) δ 7.78 (d, J = 7.9 Hz, 1H), 7.68–7.63 (m, 1H), 7.49–7.35 (m, 4H), 7.22–6.99 (m, 4H), 5.38 (dd, J = 11.4, 9.6 Hz, 1H), 5.19 (d, J = 9.6 Hz, 1H), 5.09 (d, J = 6.9 Hz, 1H), 4.61 (t, J = 5.6 Hz, 1H), 4.23 (t, J = 6.5 Hz, 1H), 3.88 (td, J = 9.8, 7.0 Hz, 1H), 3.81–3.77 (m, 2H), 3.75 (s, 3H), 3.75 (s, 3H), 3.72–3.67 (m, 1H), 3.58 (dt, J = 11.6, 5.9 Hz, 1H). 1313C NMR (101 MHz, DMSO-d6) δ 137.2, 137.1, 132.0, 129.3, 129.1, 128.7, 126.5, 122.0, 121.6, 120.0, 119.7, 119.3, 119.2, 110.4, 110.3, 110.0, 92.2, 84.4, 75.5, 61.7, 46.8, 32.9, 32.9, 19.1. HRMS (ESI) calcd for C 24 H 25 N3NaO5 [M+Na] + 458.1686, found 458.1691.

[0271] Synthesis of Example 26 (1S,2R,3R,4S,5R)-2-Amino-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W26)

[0272] At room temperature, (3S,4S,5R)-2-Nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-Methylindole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg) and 2,2,2-Trifluoroethanol (0.4 mL) were added to a reaction tube and reacted at room temperature for 2 - 8 h. After the reaction was completed, it was concentrated. 2 mL of Raney Ni was washed with 10 mL of methanol and then dissolved in 20 mL of methanol. The crude product from the previous concentration step was dissolved in 20 mL of methanol and then added to the methanol solution of Raney Ni. It was stirred overnight under H2 conditions. The reaction solution was concentrated and purified by silica gel column chromatography (eluent: dichloromethane / methanol = 10:1) to obtain (1S,2R,3R,4S,5R)-2-Amino-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (35.2 mg, yield 36%)

[0273] The reaction equation is:

[0274]

[0275] The obtained product was measured on a nuclear magnetic resonance instrument, and the nuclear magnetic resonance data obtained were:

[0276] 11H NMR (400 MHz, DMSO-d6) δ 7.76 (d, J = 8.0 Hz, 1H), 7.59 (s, 1H), 7.34 (dd, J = 20.4, 8.0 Hz, 2H), 7.22–6.94 (m, 6H), 5.36 (s, 1H), 4.89 (d, J = 9.0 Hz, 1H), 4.16 - 4.06 (m, 4H), 3.78 - 3.74 (s, 2H), 3.72 (s, 3H), 3.70 (s, 3H), 3.48 (d, J = 29.6 Hz, 1H), 2.01 (s, 3H), 1.66 (s, 3H). 13 13C NMR (101 MHz, DMSO-d6) δ 171.4, 170.2, 137.6, 127.9, 126.6, 121.6, 121.4, 119.5, 119.0, 118.7, 111.7, 109.2, 109.1, 79.1, 78.0, 63.3, 31.5, 31.5, 19.4, 19.2. HRMS (ESI) calcd for C 28 H 32 N3O5 [M + H] + 490.2342, found 490.2335.

[0277] Example 27 Synthesis of (1R,2R,3R,4S,5R)-2-nitro-2-D-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (W27)

[0278] Add (3S,4S,5R)-2-nitro-3,4-diacetoxy-5-acetoxymethylpyranose-1-ene (63.4 mg, 0.2 mmol), 1-methyl-3-D-indole (57.6 mg, 0.44 mmol), MS molecular sieve (100 mg) to 0.4 mL of 2,2,2-trifluoroethanol-d3, react at room temperature for 2 - 8 h, concentrate the reaction solution under reduced pressure, and purify the obtained crude product by silica gel column chromatography (eluent: n-hexane / acetone = 8:1) to obtain (1R,2R,3R,4S,5R)-2-nitro-2-D-1,3-bis(1-methyl-3-indolyl)-4-acetoxy-5-acetoxymethylpyranose (65.5 mg, yield 62%).

[0279] The reaction equation is:

[0280]

[0281] Measure the obtained product on a nuclear magnetic resonance instrument, and the obtained nuclear magnetic resonance data are:

[0282] 1 1H NMR (400 MHz, CDCl3) δ) 7.83 (d, J = 7.9 Hz, 2H), 7.48 (s, 1H), 7.40–7.24 (m, 4H), 7.21 (t, J = 7.1 Hz, 2H), 7.07 (s, 1H), 6.27 (d, J = 5.6 Hz, 1H), 5.65 (dd, J = 12.5, 6.3 Hz, 0.38H), 5.28 (t, J = 10.2 Hz, 1H), 4.52–4.39 (m, 1H), 4.21 (dd, J = 12.3, 5.4 Hz, 1H), 3.97 (dd, J = 12.3, 2.3 Hz, 1H), 3.92 - 3.88 (m, 1H), 3.87 (s, 3H), 3.77 (s, 3H), 1.98 (s, 3H), 1.64 (s, 3H); 13 13C NMR (101 MHz, CDCl3) δ 170.8, 169.2, 136.9, 136.8, 127.8, 127.7, 127.6, 122.7, 122.1, 120.0, 119.9, 119.3, 118.9, 109.6, 109.4, 105.9, 86.2, 72.0, 71.0, 71.0, 69.8, 62.6, 37.7, 33.2, 33.0, 29.7, 20.8, 20.0; HRMS (ESI) calcd for C 28 H 28 DN3NaO7 [M + Na] + 543.1960, found 543.1959.

[0283] Example 28 Activity Test

[0284] The concentration of doxorubicin hydrochloride (Dox) was 10 μM, and the concentrations of the remaining compounds (W1 - W27) were 20 μM. The cytotoxic activities of the following cancer cells or tumor cells (786 - O human renal clear cell adenocarcinoma cells, MKN - 45 human gastric cancer cells, A549 human lung cancer cells, HCT116 human colon cancer cells, 5637 human bladder cancer cells, GBC - SD human gallbladder cancer cells, HepG2 human liver cancer cells, DU145 human prostate cancer cells, MCF7 human breast cancer cells, A - 673 human rhabdomyosarcoma cells, SF126 human brain tumor cells, CAL - 62 human thyroid cancer cells, A - 375 human malignant melanoma cells) were tested by the CCK - 8 method. The results are as Figure 1 shown, and compounds W19, W20, and W22 have relatively broad activities against different cancer cells or tumor cells.

[0285] In addition, refer to Figure 2As shown, compounds W23 and W25 have good anti-Parkinson activity at a concentration of 50 μM, and significantly improve the rescue activity of MPP + -damaged SHSY5Y cells compared with the model group. Compounds W3 and W25 showed significant activity at 1 μM.

[0286] The embodiments described above are only descriptions of the preferred embodiments of the present invention, and do not limit the scope of the present invention. Without departing from the design spirit of the present invention, various deformations and improvements made by those of ordinary skill in the art to the technical solutions of the present invention shall fall within the protection scope determined by the claims of the present invention.

Claims

1. An indole glycoside compound and a pyrrole glycoside compound, characterized in that: The structural formula is shown as any one of the following compounds: 。 2. The synthesis method of the indolyl glycoside compounds and pyrrolyl glycoside compounds according to claim 1, characterized in that: A nitroalkene sugar, a first molecule of a substituted indole or a substituted pyrrole, and a molecular sieve are stirred in an organic solvent for 6 to 12 h to form a 1,3-bisindole-2-nitro sugar compound or a 1,3-bispyrrole-2-nitro sugar compound.

3. A method for synthesizing an indolyl glycoside compound and a pyrrolyl glycoside compound according to claim 2, wherein: The equivalent ratio of the nitroalkene sugar to the first molecule of the substituted indole or the substituted pyrrole is 1:1 to 10, the concentration of the organic solvent is 0.001 to 100 mol / L, the reaction temperature is -100 to 200 °C, and the concentration of the molecular sieve is 10 to 500 g / moL.

4. A method for synthesizing an indole glycoside compound and a pyrrole glycoside compound according to claim 2, characterized in that: The organic solvent is any one or a mixture of any proportion of several solvents selected from 2,2,2-trifluoroethanol, 2,2,2-trichloroethanol, 1,1,1,3,3,3-hexafluoro-2-propanol, chloroethanol, 2,2-dichloroethanol, dichloromethane, chloroform, acetonitrile, methanol, ethanol, tert-butanol, isopropanol, benzene, toluene, tetrahydrofuran, N,N-dimethylformamide, DMSO, 1,4-dioxane, 2-methyl-tetrahydrofuran, ether, tert-butyl methyl ether.

5. The synthesis method of an indole glycoside compound and a pyrrole glycoside compound according to claim 2, wherein: A catalyst is added to the reaction system of the nitroalkene sugar and the first molecule of the substituted indole or the substituted pyrrole. The dosage of the catalyst is 0.001 to 10.0 equivalents, and the catalyst includes any one of BF3∙Et2O, TMSOTf, TBSOTf, TESOTf, metal halides, metal sulfonates, perchloric acid and its metal salts, triarylboron, organic phosphoric acid, and organic carbonyl acids.

6. The synthesis method of an indole glycoside compound and a pyrrole glycoside compound according to claim 2, characterized in that: After adding the first molecule of the substituted indole or the substituted pyrrole and stirring the reaction until the nitroalkene sugar reacts completely, a second molecule of the substituted indole or pyrrole is added to the reaction system to form a 1,3-bisindole-2-nitro sugar compound or a 1,3-bispyrrole-2-nitro sugar compound. The indole or pyrrole at the 1-position and the 3-position in the 1,3-bisindole-2-nitro sugar compound or the 1,3-bispyrrole-2-nitro sugar compound is different, and the equivalent of the second molecule of the substituted indole or pyrrole is 1.0 to 10.

0.

7. A pharmaceutical composition, characterized in that: It includes the compound or its salt according to claim 1, and a pharmaceutically acceptable carrier.

8. Use of the compound or its salt according to claim 1 or the pharmaceutical composition according to claim 7 in the preparation of drugs for treating Parkinson's disease and tumors, wherein the tumors include renal clear cell adenocarcinoma, gastric cancer, lung cancer, colon cancer, bladder cancer, gallbladder cancer, liver cancer, prostate cancer, breast cancer, rhabdomyosarcoma, brain tumor, thyroid cancer, or malignant melanoma.

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