A method for synthesizing 1,1'-thiodisaccharides with high stereoselectivity using organic catalysis

Abstract

The present invention belongs to the technical field of organic synthesis, and in particular to a method for synthesizing 1,1'-thiodisaccharides with high stereoselectivity by organic catalysis. The present invention first screens the reaction conditions and the amount of substrate, and then uses the reaction of 2-nitro sugar ene and glycosyl mercaptan to synthesize galactose-type 1,1'-thiodisaccharides with high stereoselectivity under the catalysis of bifunctional organic thiourea. At the same time, the present invention further synthesizes glucose-type 1,1'-2-nitrothiodisaccharides. The present invention also applies the synthesis method to the synthesis of thio-1,1'-2,2'-diacetylaminodisaccharide fragments of the biologically active natural product tunicamycin. The method of the present invention has the characteristics of good α selectivity, high yield, mild reaction conditions, wide substrate range, etc., is easy to realize large-scale batch production, and has important application prospects.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and in particular relates to a method for synthesizing 1,1'-thiodisaccharide with high stereoselectivity through organic catalysis. Background Art

[0002] Non-reducing 1,1'-disaccharides are widely distributed in plants, fungi, yeasts, red algae, lichens and insects, and are structural motifs of many natural products, such as trehalose, trehalosamine, tunicamycin, tunicamycin and avilamycin. 1,1'-disaccharides play an important role in preventing cell damage during drying and protecting cells and their components from other stress conditions. Tunicamycin has a scaffold structure of 1,1'-2,2'-diaminodisaccharide and exhibits excellent antibacterial and antitumor activities, while aminodeoxytrehalose derivatives have strong antibacterial activity. In addition, thioglycosides, as classic analogs of natural O-glycosides, are resistant to enzyme and acid hydrolysis and have many applications in glycobiology and drug development. Therefore, 1,1'-thiodisaccharides have become potential sugar mimetics for bioactivity research.

[0003] Thanks to the efforts of carbohydrate chemists, different methods for the synthesis of 1,1'-thiodisaccharides have been developed in recent years, including the traditional Lewis acid-catalyzed glycosylation of glycosyl donors with glycosyl thiols, the glycosylation of glycosyl halides with glycosyl thiols, the metal-catalyzed glycosylation of glycosyl tributyltin with glycosyl sulfosuccinimide, the rhenium (V)-catalyzed glycosylation of glycoenes with glycosyl thiols, and the photoinitiated thiol-ene reaction between 2-substituted glycoenes and glycosyl thiols.

[0004] Despite these important advances, challenges remain, including stoichiometric activators, relatively harsh reaction conditions, and stereoselectivity issues. At the same time, 2-nitroglycosides are considered to be important synthons for the synthesis of 2-amino-2-deoxyglycosides. To this end, the present invention provides a new method for synthesizing 1,1'-thiodisaccharides with high stereoselectivity by reacting 2-nitroglycosides with glycosylthiols under the catalysis of bifunctional organic thioureas, as shown in the following formula.

[0005]

[0006] At the same time, the method is also applied to the synthesis of the thio-1,1'-2,2'-diacetylamino disaccharide fragment of the biologically active natural product tunicamycin. The method is easy to achieve large-scale batch production and has important application prospects. Summary of the invention

[0007] The object of the present invention is to provide a method for synthesizing 1,1'-thiodisaccharides with high stereoselectivity by organic catalysis, which can efficiently synthesize thiodisaccharide compounds.

[0008] In order to achieve the above technical objectives, the present invention adopts the following technical solutions:

[0009] A class of 1,1'-thiodisaccharides, the general structure of which is shown below:

[0010]

[0011] Wherein, R1 is Bn, TIPS, TBS or Ac.

[0012] R2 is Bn, TIPDS or Ac.

[0013] R3 is Bn, TIPDS, TBS or Ac.

[0014] R4 is -NO2 or -NHAc.

[0015] R5 is

[0016] More preferably, for

[0017] Specifically, Ac is an acetyl group, Bn is a benzyl group, TIPS is a triisopropylsilyl group, TBS is a tert-butyldimethylsilyl group, and TIPDS is a 1,1,3,3-tetraisopropyl-1,3-disiloxane group.

[0018] Furthermore, the present invention also provides a method for preparing the 1,1'-thiodisaccharide, comprising the following steps:

[0019] The 2-nitroglycoside donor and acceptor 1 are dissolved in solvent 1, and then catalyst 1 is added and stirred at 0 to 20° C. (preferably 0° C.) for 1-2 h (preferably 1.5 h), followed by TLC analysis, concentration under reduced pressure, and purification to obtain a 1,1'-thiodisaccharide product.

[0020] Specifically, receptor 1 is a glycosyl thiol receptor.

[0021] Specifically, the 2-nitroglycoside donors are 1a, 1b, 5a, 5b, 5c, and have the structural formula:

[0022]

[0023]

[0024] The glycosyl thiol acceptor is 2a-2g, and the structural formula is:

[0025]

[0026] Specifically, the molar ratio of the 2-nitroglycoalkene donor to the acceptor 1 is 1:(1-2), preferably 1:1.2.

[0027] Specifically, catalyst 1 is thiourea 3a-e, and the structural formula is:

[0028]

[0029] Specifically, the molar ratio of the receptor 1 to the catalyst 1 is (10-12):1, preferably 12:1.

[0030] Specifically, solvent 1 is DCM, Tol, CH3CN or THF.

[0031] Specifically, the concentration of solvent 1 is 0.1-0.5M, preferably 0.1M.

[0032] Based on a general inventive concept, when R5 is When the 1,1'-thiodisaccharide is a galactose-type 1,1'-2-nitrothiodisaccharide or the 1,1'-thiodisaccharide is a glucose-type 1,1'-2-nitrothiodisaccharide, the general structural formula of the galactose-type 1,1'-2-nitrothiodisaccharide is:

[0033]

[0034] Specifically, in the galactose-type 1,1'-2-nitrothiodisaccharide, R1 is Bn or TIPS, R2 is Bn, R3 is Bn, and R4 is -NO2.

[0035] The general structural formula of the glucose-type 1,1'-2-nitrothiodisaccharide is:

[0036]

[0037] Specifically, in the glucose-type 1,1'-2-nitrothiodisaccharide, R1 is Bn, TBS or TIPS, R2 is Bn or TIPDS, R3 is Bn, TBS or TIPDS, and R4 is -NO2.

[0038] Preferably, the for

[0039] More preferably, the galactose-type 1,1'-2-nitrothiodisaccharide is a compound with the following structure:

[0040]

[0041] Further preferably, the glucose-type 1,1'-2-nitrothiodisaccharide is a compound with the following structure:

[0042]

[0043] Based on a general inventive concept, when R5 is When the 1,1'-thiodisaccharide is 1,1'-2,2'-diacetylaminodisaccharide, the structural formula of which is as follows:

[0044]

[0045] Specifically, in the 1,1'-2,2'-diacetylamino disaccharide, R1 is Ac, R2 is Ac, R3 is Ac, and R4 is -NHAc.

[0046] The preparation method of the 1,1'-2,2'-diacetylamino disaccharide comprises the following steps:

[0047] (1) dissolving a 2-nitroglycoside donor and an acceptor 1 in a solvent 1, then adding a catalyst 1 and stirring the mixture at 0 to 20° C. (preferably 0° C.) for 1 to 2 h (preferably 1.5 h), followed by TLC analysis, concentrating under reduced pressure, and purifying to obtain a 1,1'-thiodisaccharide product;

[0048] (2) dissolving the 1,1'-thiodisaccharide product obtained in step (1) in solvent 2, cooling to -5 to 5°C (preferably 0°C), reducing and acetylating, and then stirring the reaction at -5 to 5°C (preferably 0°C) for 1-2h (preferably 2h), concentrating, and purifying to obtain an intermediate product;

[0049] (3) The intermediate product in step (2) is dissolved in solvent 3 and cooled to -5 to 5°C (preferably 0°C), then solvent 4 is added, the reaction temperature is raised to room temperature (20-25°C) and the reaction is carried out for 1-2h (preferably 1.5h), purified to obtain a crude product, and then the crude product is dissolved in solvent 5 and cooled to -5 to 5°C (preferably 0°C), catalyst 2 and reagent 1 are added, the temperature is raised to room temperature (20-25°C) and the reaction is stirred for 1-2h (preferably 2h), diluted, washed, dried, filtered, concentrated in vacuo, purified to obtain the final product.

[0050] Specifically, the 2-nitroglycoside donor is 5c and the acceptor 1 is 2g.

[0051] Specifically, the molar ratio of the 2-nitroglycoalkene donor to the acceptor 1 is 1:(1-2), preferably 1:1.2.

[0052] Specifically, catalyst 1 is thiourea 3a-e.

[0053] Specifically, the molar ratio of the receptor 1 to the catalyst 1 is (10-12):1, preferably 12:1.

[0054] Specifically, solvent 1 is DCM, Tol, CH3CN or THF.

[0055] Specifically, the concentration of solvent 1 is 0.1-0.5M, preferably 0.1M.

[0056] Specifically, in step (2), zinc powder and anhydrous copper sulfate are used for reduction, and acetic acid and acetic anhydride are used for acetylation.

[0057] Specifically, solvent 2 is a mixed solvent of THF and H2O, wherein the volume ratio of THF to H2O is 10:1.

[0058] Specifically, solvent 3 is Py, or a mixed solvent of THF and Py, wherein the volume ratio of THF to Py is 1:1.

[0059] Specifically, solvent 4 is Py, or a mixed solvent of HF and Py.

[0060] Specifically, solvent 5 is Py, or a mixed solvent of THF and Py, wherein the volume ratio of THF to Py is 1:1.

[0061] Specifically, the catalyst 2 is 4,4-dimethylaminopyridine or pyridine.

[0062] Specifically, reagent 1 is acetic anhydride.

[0063] Compared with the prior art, the advantages of the present invention are:

[0064] 1. The present invention first screened the reaction conditions and substrate dosage, and then synthesized galactose-type 1,1'-2-nitrothiodisaccharides 4a-f using 2-nitroglycoside donors 1a-b and glycosylthiol acceptors 2a-f under the catalysis of bifunctional organic thiourea. At the same time, the present invention further synthesized glucose-type 1,1'-2-nitrothiodisaccharides 6a-h.

[0065] 2. The present invention also applies the synthesis method to the synthesis of the thio-1,1'-2,2'-diacetylamino disaccharide fragment of the biologically active natural product tunicamycin. The method of the present invention has the characteristics of good α selectivity, high yield, mild reaction conditions, and a wide range of substrates, and is easy to achieve large-scale batch production, and has important application prospects. DETAILED DESCRIPTION

[0066] The technical solution of the present invention is further described in detail below through specific embodiments, but the protection scope of the present invention is not limited thereto.

[0067] The abbreviations involved in the embodiments of the present invention include: Ac is acetyl, Bn is benzyl, Me is methyl, TIPS is triisopropylsilyl, Bz is benzoyl, Tf is trifluoromethanesulfonate, DMAP is 4,4-dimethylaminopyridine, DMF is dimethylformamide, DCM is dichloromethane, TEA is triethylamine, Boc is tert-butyloxycarbonyl, Tol is toluene, THF is tetrahydrofuran, TBS is tert-butyldimethylsilyl, TIPDS is 1,1,3,3-tetraisopropyl-1,3-disiloxane, i Pr is isopropyl, Py is pyridine, PE is petroleum ether, and EA is ethyl acetate. The reagents used in the present invention are all commercially available products.

[0068] Example 1 A method for synthesizing 1,1'-thiodisaccharides with high stereoselectivity by organic catalysis

[0069] 1.1 Optimization of reaction conditions

[0070] The present invention first synthesizes 1,1'-thiodisaccharide by using 3,4,6-tri-O-benzyl-2-nitropentanal 1a as a donor and 2,3,4,6-tetra-O-galactosylthiol 2a as an acceptor, optimizes the catalyst, reaction conditions, etc., and screens a series of catalysts (thiourea 3a and bifunctional organic thioureas 3b-e, wherein catalyst 3a-e can be a common commercially available reagent in the prior art), and the results are shown in Table 1.

[0071]

[0072] Table 1 Optimization of reaction conditions

[0073]

[0074] a The α / β ratio is 1 The results were confirmed by H NMR analysis. b The reaction temperature was 20°C.

[0075] As can be seen from Table 1, the reaction using catalyst 3d at 0°C has the best stereoselectivity and high yield (only α configuration, reaction yield is 92%).

[0076] Next, the present invention investigated the effect of different solvents on the reaction, mainly investigating the solvents as DCM, Tol, CH3CN and THF. The results showed that using DCM and Tol as solvents had better stereoselectivity, and the yield using DCM as solvent was slightly higher (as shown in Table 1).

[0077] As for the amount of solvent, when the amount of catalyst is reduced to 0.05 equivalents, the reaction can maintain good stereoselectivity, but the yield is slightly lower; when the amount of catalyst is increased to 0.2 equivalents, the stereoselectivity decreases to 10:1. If the amount of acceptor is increased to 1.2 equivalents, the reaction yield can be as high as 97% and the stereoselectivity is maintained. However, when the reaction temperature is higher, the reaction yield decreases slightly.

[0078] 1.2 Synthesis of galactose-type 1,1'-2-nitrothiodisaccharides 4a-f

[0079] Under the condition of optimizing the reaction conditions, the present invention selects the applicable scope of the substrate for the bifunctional organic thiourea-catalyzed thioglycosidation reaction, the donor of the reaction is 2-nitroglycoside 1a-b, the acceptor is glycosyl thiol 2a-f, and the acceptor specifically includes 2,3,4,6-tetra-O-galactosyl thiol 2a, 2,3,4,6-tetra-O-pyranose glucopyranosyl thiol 2b, 2,2,4,4,5-tetra-O-mannosyl thiol 2c, 2-acetylamino-3,4,6-tri-O-pyranose glucopyranosyl thiol 2d, and disaccharide glycosyl thiol 2e-f, wherein 1a adopts the literature (Das J, Schmidt R R. Convenient Glycoside Synthesis of AminoSugars: Michael-Type Addition to 2-Nitro-D-galactal [J]. European journal of organic Chemistry, 1998, 1998(8):1609-1613.), 1b was synthesized by the method in the literature (Medina S, Harper MJ, Balmond EI, et al. Stereoselective glycosylation of 2-nitrogalactals catalyzed by a bifunctional organocatalyst[J]. Organic letters, 2016, 18(17):4222-4225.), 2a-b, 2d, 2g were synthesized by the method in (Wojcik F, Lel S, O'Brien AG, et al. Synthesis of homo-and heteromultivalent carbohydrate-functionalized oligo(amidoamines)using novel glyco-building blocks[J]. Beilstein J. Org. Chem. 2013, 9, 2395-2403), 2c was synthesized by the method in the literature (Fiore M, Marra A, Dondoni A. Photoinduced thiol-ene coupling as a click ligation tool forthiodisaccharide synthesis[J].The Journal of organic chemistry,2009,74(11):4422-4425.) was synthesized by the method in the literature (Fujihira T, Chida M, Kamijo H, et al. Novel synthesis of 1-thioglycopyranoses via thioiminium salts [J]. Journal of carbohydrate chemistry, 2002, 21 (4): 287-292), and 2f was synthesized by the method in the literature (Ishido Y, Kanbayashi N, Fujii N, et al. Folding control of a non-natural glycopeptide using saccharide-coded structural information for polypeptides [J]. Chemical Communications, 2020, 56 (18): 2767-2770.). The specific 2-nitroglycosylated donor substrate selection range and reaction formula are as follows:

[0080]

[0081] In the reaction formula, all reactions were performed with donor (1 equivalent), acceptor (1.2 equivalents) and 10 mol% bifunctional organic thiourea catalyst 3d in DCM at 0 °C for 1.5 h and 1 H NMR analysis determined the α / β ratio.

[0082] As can be seen from the reaction formula, 3,4,6-tri-O-benzyl-2-nitrosugar donor 1a can be effectively glycosylated with a variety of glycosyl thiols, and this reaction can also obtain the desired 1,1'-2-nitrothiodisaccharides 4a-f with a yield of 91-98% and excellent α selectivity. In addition, during the reaction, 3,4-di-O-benzyl-6-O-triisopropylsilyl 2-nitrosugar donor 1b can react smoothly with glycosyl thiols 2a and 2b to produce the desired products 4g-h with high yields and excellent α selectivity.

[0083] 1.3 Glucose-type 1,1'-2-nitrothiodisaccharide 6a-h

[0084] After successfully achieving stereoselective sulphosylation of 2-nitrogalactose, the present invention also carried out stereoselective sulphosylation of 2-nitroglucose, wherein 5a was synthesized by the method in the literature (Vedachalam S, Tan SM, Teo HP, et al. N-Heterocyclic Carbene Catalyzed C-Glycosylation: A Concise Approach from Stetter Reaction [J]. Organic letters, 2012, 14 (1): 174-177.). The specific selection range of 2-nitroglucose donor substrate and reaction formula are as follows:

[0085]

[0086] In the reaction formula, all reactions were performed with donor (1 equivalent), acceptor (1.2 equivalents) and 5 mol% bifunctional organic thiourea catalyst 3d in DCM at 0 °C for 1.5 h and 1 H NMR analysis determined the α / β ratio.

[0087] Using similar reaction conditions as the aforementioned 2-nitroglucose donor substrate, 3,4,6-tri-O-benzyl-2-nitroglucose donor 5a reacted with galactosylthiol 2a to obtain a mixture of glucose-type and mannose-type 1,1'-2-nitrothiodisaccharide 6a (α-glu: β-glu: α-mann = 17:1:6) with a yield of 96%. In addition, when 2-nitroglucose donor 5b having a large number of protecting groups (tert-butyl, dimethyl, silyl) at C3 and C6 positions was glycosylated by acceptor 2a, the reaction also obtained a mixture of glucose-type and mannose-type 1,1'-2-nitrothiodisaccharide 6b (α-glu: β-glu: α-mann = 4:1:2) with a yield of 95%.

[0088] As can be seen from the reaction equation, the conformationally constrained 3,4-O-(tetraisopropyldisiloxane)-glucene / 2-nitroglucene was demonstrated to be an effective donor for the selective construction of 2-deoxy-1-O-α-glycosides and 2-amino-2-deoxy-1-O-α-glycosides, thereby preparing 3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-2-nitroglucene 5c. This conformationally constrained 2-nitroglucene 5c was smoothly glycosylated with a variety of glycosyl thiols (including monosaccharide glycosyl thiols 2a-d and disaccharide glycosyl thiols 2e-f) to finally afford the desired 1,1'-2-nitrothiodisaccharides 6c-h in 94-98% yields with excellent α selectivity.

[0089] 1.4 Synthesis of 1,1'-2,2'-diacetylamino disaccharide fragment of tunicamycin

[0090] Furthermore, the present invention adopts the aforementioned bifunctional organic thiourea catalytic reaction conditions to synthesize tunicamycin disaccharide fragments, and the specific reaction formula is as follows:

[0091]

[0092] In the reaction formula, donor 5c was used to glycosylate with 2-acetamido-3,4,6-tri-O-galactosylpyranthiol 2g to obtain compound 7 (1,1'-2-nitro-2'-acetamidothiodisaccharide) with a yield of 97%. This reaction has excellent stereoselectivity. Then, Zn / AcOH / CuSO4 / Ac2O was used to reduce and acetylate the nitro group in compound 7 to obtain compound 8 with a yield of 71%. Finally, based on compound 8, the silyl group was removed and the acetyl group was added to generate compound 9 with a yield of 65%.

[0093] In summary, the present invention provides a method for synthesizing 1,1'-2-nitrothiodisaccharides using 2-nitroglycosides and glycosylthiols under bifunctional organic thiourea catalysis. The method is carried out under very mild reaction conditions and has excellent stereoselectivity and high yield when using a variety of substrates. On this basis, the present invention also synthesized tunicamycin 1,1'-2,2'-diacetylaminodisaccharide fragments.

[0094] 1.5 Reaction procedure and specific ratio of raw materials used for each compound

[0095] The general procedure of the bifunctional organic thiourea-catalyzed glycosylation reaction of the present invention is:

[0096] 2-Nitroglycoside (1.0 equivalent) and glycosylthiol (1.2 equivalent) were dissolved in dry DCM (0.1 M); then catalyst 3d (0.1 equivalent) was added and the reaction was stirred at 0°C for 1.5 hours and monitored by TLC analysis. Finally, the reaction mixture was concentrated under reduced pressure. The residue during the reaction was purified by size exclusion chromatography (DCM: MeOH = 1: 1) to obtain the corresponding 1,1'-thiodisaccharide product.

[0097] Notes on the experimental method of the present invention:

[0098] All moisture-sensitive reactions were performed under an argon atmosphere. Solvents used in glycosylation reactions (CH2Cl2, Tol, THF, CH3CN) were distilled over CaH2 and stored in activated The reactions were monitored by TLC analysis, detected by UV (254 nm) and, where applicable, by sparging with 20% sulfuric acid in EtOH or using (NH4)6Mo7O 24 ·4H2O (25 g / L) solution and (NH4)4Ce(SO4)4·2H2O (10 g / L) were tested in 10% sulfuric acid (aqueous solution) and then carbonized at about 150°C. Flash column chromatography was performed on silica gel (300-400 mesh). CDCl3, CD3OD, CD3COCD3 were recorded on a Bruker AV 400. 1 H and 13 C spectrum. Relative to tetramethylsilane (CdCl in 1 HNMR) or residual signals of deuterated solvents, chemical shifts (δ) are in ppm. Coupling constants (J) are in Hz. All 13 C spectra were all proton-decoupled. COSY, HSQC, NOESY, and HMBC experiments were used to further elucidate the structures where applicable.

[0099] Specifically, the dosage ratios of the compounds and raw materials in the present invention are as follows:

[0100] Synthesis of 3,6-di-O-tert-butyldimethylsilyl-4-O-benzyl-2-nitrodextran (5b):

[0101] 3,6-di-O-tert-butyldimethylsilyl-4-O-benzyl glucan (464.8 mg, 1.0 mmol), tetrabutylammonium nitrate (426.3 mg, 1.4 mmol) and 2,6-di-tert-butyl-4-methylpyridine (410.7 mg, 2 mmol) were dissolved in dry CH2Cl2 (5 mL, 0.2 M), the reaction mixture was cooled to -70 °C, and then Tf2O (0.24 mL, 1.4 mmol) was added. The reaction mixture was stirred at the same temperature for 5 minutes and monitored by TLC analysis. After completion of the reaction, the reaction mixture was diluted with CH2Cl2, the suspension was filtered and washed with CH2Cl. The filtrate was washed with 1M HCl, brine, dried over Na2SO4, and concentrated under reduced pressure. After purification by column chromatography (40:1, PE:EA), 2-nitroglycoside (5b) was obtained as a light yellow foam solid (249.8 mg, 49%). [α] D 35 +38.3 (c=0.5, CHCl3); 1H NMR (400MHz, CDCl3) δ8.20 (s, 1H), 7.40-7.29 (m, 5H), 4.81 (t, J=2.2Hz, 1H), 4-64 (d, J=12.3Hz, 1H), 4.61 -4.55 (m, 2H), 3.91 (dd, J=11.7, 8.2Hz, 1H), 3.74-3.67 (m, 2H), 0.88 (s, 9H), 0.80 (s, 9h), 0.; 09 (s, 3H), 0. 13 C NMR (100 MHz, CDCl3) δ 153.8, 136.8, 132.1, 128.7, 128.4, 127.9, 80.8, 73.1, 71.6, 61.63, 61.57, 25.9, 25.6, 18.3, 17.9, -5.0, -5.1, -5.29, -5.32. Calculated C 25 H 44 NO6Si2(M+H) + HRMS (ESI) of M / z 510.2707, found 510.2707.

[0102] Among them, the compound 3,6-di-O-tert-butyldimethylsilyl-4-O-benzyl glucan was synthesized by the method in the literature (Berlin WK, Zhang WS, Shen TY. Glycosyl-inositol derivatives: III. Synthesis of hexosamine-inositolphosphates related to putative insulin mediators [J]. Tetrahedron, 1991, 47 (1): 1-20.).

[0103] Synthesis of 3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-2-nitrodextran (5c):

[0104] 3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyldextran (545.0 mg, 1.0 mmol), tetrabutylammonium nitrate (426.3 mg, 1.4 mmol), 2,6-di-tert-butyl-4-methylpyridine (410.7 mg, 2 mmol) and MS (500 mg) was dissolved in dry CH2Cl2 (5 ml, 0.2 M), the reaction mixture was cooled to -30 °C, and then 0.24 ml, 1.4 mmol of Tf2O was added. The reaction mixture was stirred at the same temperature for 5 minutes and monitored by TLC analysis. After the reaction was completed, the reaction mixture was diluted with CH2Cl2, the suspension was filtered and washed with CH2Cl. The filtrate was washed with 1M HCl, brine, dried over Na2SO4 and concentrated under reduced pressure. After purification by column chromatography (90:1, PE:EA), 2-nitroglycoside (5c) was obtained as a white foam solid (324.5 mg, 55%). [α] D 35 +224 (c=0.38, CHCl3); 1 H NMR 1H (400MHz, CDCl3) δ8.01 (s, 1H), 4.91 (d, J = 6.2Hz, 1H), 4.16 (dd, J = 11.5, 1.8Hz, 1H), 4.06 (dd, J = 10.6, 6.2Hz ,1H),4.00(dd,J=11.5,4.8Hz,1H),3.89(ddd,J=10.7,4.7,1.6Hz,1H),1.19-1.15(m,7H),1.10-0.98(m,42H). 13 C NMR (100 MHz, CDCl3) δ 153.8, 133.1, 81.9, 72.1, 71.1, 61.8, 17.93, 17.89, 17.6, 17.42, 17.38, 17.2, 17.14, 17.10, 17.00, 16.96, 13.1, 13.0, 12.44, 12.38, 12.0. Calculated C 27 H 56 NO7Si3(M+H) + HRMS (ESI) of M / z 590.3365, found 590.3364.

[0105] Among them, 3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl glucan was synthesized by the method in the literature (Balmond E I, Benito-Alifonso D, Coe DM, et al. A 3,4-trans-Fused Cyclic Protecting Group Facilitates α-Selective Catalytic Synthesis of 2-Deoxyglycosides [J]. Angewandte Chemie, 2014, 126 (31): 8329-8333.).

[0106] Compound 4a includes two configurations, α and β. The synthesis method is as follows: the reaction is carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2a (43.7 mg, 0.12 mmol). The product is purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). Among them, 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-pyranogalactoside (4a-α) is a compound in the form of a white foam solid (80.1 mg, 97% yield, only α, PE:EA=1:1, Rf=0.4). [α] D 25 +79.6 (c=1.33, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.40-7.26(m,12H),7.26-7.18(m,3H),5.90(d,J=5.8Hz,1H),5.37(d,J=3.1Hz,1H),5.25(dd,J=10 .6,4.8Hz,1H),5.20(d,J=10.0Hz,1H),4.98(dd,J=10.0,3.2Hz,1H),4.82(d,J=11.0Hz,1H),4.69(s,2H),4.53(d,J=10. 0Hz,1H),4.47(m,2H),4.42(d,J=11.6Hz,1H),4.32-4.25(m,1H),4.21(dd,J=10.9,2.8Hz,1H),4.08-3.97(m,3H),3.86( t,J=6.7Hz,1H),3.61(t,J=8.4Hz,1H),3.55(dd,J=8.7,5.6Hz,1H),2.14(s,3H),2.04(s,3H),2.00(s,3H),1.97(s,3H); 13 C NMR (100 MHz, CDCl3) δ 170.3, 170.2, 170.0, 169.5, 137.8, 137.6, 136.9, 128.6, 128.5, 128.4, 128.23, 128.20, 128.1, 127.93, 127.90, 84.3, 84.2, 82.5, 75.6, 75.4, 74.7, 73.6, 73.01, 71.8, 71.1, 67.9, 67.4, 67.0, 60.9, 20.68, 20.66, 20.6. Calculated C 41 H 47 NO 15 SNa(M+Na) +HRMS (ESI) of M / z 848.2564, found 848.2601.

[0107] 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-β-D-galactopyranoside (4a-β), a white solid; [α] D 25 +8.0 (c=0.64, CHCl3); 1 HNMR (400MHz, CDCl3) δ7.40-7.28(m,12H),7.26-7.20(m,3H),5.34(d,J=2.9Hz,1H),5.17(t ,J=10.1Hz,1H),5.02-4.90(m,3H),4.88(d,J=11.2Hz,1H),4.73(d,J=10.2Hz,1H),4.62(d,J =11.5Hz,1H),4.55(d,J=11.2Hz,1H),4.51-4.43(m,3H),4.12-4.05(m,2H),4.05-3.98(m,2H ),3.72-3.66(m,2H),3.65-3.54(m,2H),2.12(s,3H),2.05(s,3H),2.02(s,3H),1.97(s,3H). 13 C NMR (100 MHz, CDCl3) δ 170.31, 170.30, 170.0, 169.6, 137.8, 137.5, 136.4, 128.7, 128.6, 128.5, 128.4, 128.3, 128.10, 128.08, 128.0, 127.9, 86.8, 81.2, 80.5, 79.5, 77.9, 74.9, 74.4, 73.7, 72.5, 71.8, 71.43, 68.0, 67.1, 67.0, 61.1, 20.8, 20.71, 20.68, 20.6. Calculated C 41 H 47 NO 15 SNa(M+Na) + HRMS (ESI) of m / z 848.2564, found 848.2599.

[0108] 1-S-(2.3.4.6-tetra-O-acetyl-1-thio-β-D-glucopyranosyl)-3.4-6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-galactopyranoside (4b):

[0109] The reaction was carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2b (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 4b (78.5 mg, 95% yield, only α, PE: EA = 2: 1, Rf = 0.3) was obtained. [α] D 35 +68.0 (c=1.50, CHCl3); 1 H NMMR (400MHz, CDCl3) δ7.38-7.26(m,13H),7.24-7.19(m,2H),5.92(d,J=5.8Hz,1H),5.26(dd,J=10.9,5.8Hz,1H),5.13(t ,J=9.2Hz,1H),5.06(t,J=9.6Hz,1H),5.03-4.96(m,1H),4.82(d,J=11.0Hz,1H),4.69(s,2H),4.55(d,J=10.1Hz,1H),4.50 -4.44(m,2H),4.40(d,J=11.5Hz,1H),4.30(t,J=6.7Hz,1H),4.22(dd,J=10.9,2.9Hz,1H),4.12(dd,J=12.5,4.1Hz,1H),4 .02(d,J=2.4Hz,1H),3.98(dd,J=12.5,2.1Hz,1H),3.62-3.53(m,3H),2.04(s,3H),2.03(s,3H),2.00(s,3H),1.99(s,3H). 13 C NMR (100 MHz, CDCl3) δ 170.6, 170.1, 169.29, 169.28, 137.8, 137.6, 137.0, 128.6, 128.5, 128.4, 128.2, 128.1, 128.03, 127.98, 127.9, 84.1, 83.3, 81.9, 76.2, 75.7, 75.4, 73.8, 73.7, 73.2, 73.1, 71.1, 70.9, 67.8, 67.7, 61.6, 20.7, 20.58, 20.55. Calculated C 41 H 47 NO 15 SK(M+K) + HRMS (ESI) of M / z 864.2304, found 864.2314.

[0110] 1-S-(2.3.4.6-Tetra-O-acetyl-1-thio-β-D-mannopyranyl)-3.4-6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-galactopyranoside (4c):

[0111] The reaction was carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2c (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 4c (79.3 mg, yield 96%, only α, PE: EA = 2: 1, Rf = 0.3) was obtained. [α] D 35 +143.0 (c=1.60, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.39-7.25(m,13H),7.24-7.18(m,2H),5.87(d,J=5.9Hz,1H),5.37(s,1H),5.35(dd,J=3.3, 1.2Hz,1H),5.33-5.29(m,1H),5.29(s,1H),5.12(dd,J=10.1,3.4Hz,1H),4.82(d,J=11.0Hz,1H),4.72(s,2H),4.5 1-4.44(m,2H),4.41(d,J=11.7Hz,1H),4.31-4.23(m,2H),4.21(dd,J=8.0,2.9Hz,1H),4.16-4.07(m,2H),4.02(d, J=2.3Hz,1H),3.63-3.56(m,1H),3.53(dd,J=9.2,5.9Hz,1H),2.12(s,3H),2.11(s,3H),2.05(s,3H),1.99(s,3H). 13 C NMR (100 MHz, CDCl3) δ 170.6, 169.82, 169.78, 169.7, 137.73, 137.65, 136.9, 128.6, 128.5, 128.4, 128.3, 128.2, 128.0, 127.88, 127.85, 83.8, 80.1, 79.7, 75.9, 75.4, 73.6, 73.2, 71.3, 70.4, 70.1, 69.6, 67.8, 65.6, 62.0, 26.9, 20.8, 20.7, 20.6. Calculated C 41 H 47 NO 15 SK(M+K) +HRMS (ESI) of M / z 864.2304, found 864.2318.

[0112] 1-S-(2-deoxy-2-acetylamino-3,4,6-tri-O-acetyl-1-thio-β-D-pyranoglucopyranosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-pyranoglucopyranoside (4d):

[0113] The reaction was carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2d (43.6 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 4d (76.7 mg, 93% yield, only α, PE: EA = 1: 1, Rf = 0.25) was obtained. [α] D 25 +52.2 (c=1.10, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.38-7.27(m,10H),7.25-7.20(m,2H),7.19-7.11(m,2H),7.08(d,J=7.1Hz,1H),6.19(d,J=6.1Hz,1H),5.89-5.74(m, 1H),5.44(d,J=10.2Hz,1H),5.28(dd,J=10.9,6.1Hz,1H),5.07-4.93(m,1H),4.83(d,J=11.5Hz,1H),4.77(d,J=10.7Hz,1H),4.71(d,J=10.7 Hz,1H),4.47(d,J=12.0Hz,1H),4.41(d,J=11.7Hz,2H),4.27(dd,J=12.4,4.3Hz,2H),4.18(d,J=9.5Hz,1H),4.06(dd,J=12.4,2.1Hz,1H),3. 88-3.74(m,2H),3.67-3.56(m,1H),3.50(td,J=10.3,7.2Hz,1H),3.19 (d,J=9.8Hz,1H),2.10(s,3H),2.01(s,3H),1.97(s,3H),1.68(s,3H). 13C NMR (100 MHz, CDCl3) δ 171.2, 170.7, 169.7, 137.3, 136.9, 136.3, 128.8, 128.7, 128.6, 128.5, 128.39, 128.36, 128.3, 128.22, 128.17, 83.5, 79.4, 78.0, 76.1, 76.0, 74.9, 73.9, 73.6, 73.5, 71.8, 71.5, 70.7, 69.1, 62.0, 56.3, 22.9, 20.8, 20.71, 20.67. Calculated C 41 H 49 N2O 14 S(M+H) + HRMS (ESI) of M / z was 825.2905, and the result was 825.2898.

[0114] 1-S-(2,3,4,6-tetra-O-acetyl-α-D-glucopyranosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-galactopyranoside (4e):

[0115] The reaction was carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2e (78.3 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). A colorless oily compound 4e (107.0 mg, yield 96%, only α, PE:EA=1:1, Rf=0.45) was obtained. [α] D 35 +77.4 (c=1.89, CHCl3); 1H NMR (400MHz, CDCl3) δ7.42-7.26(m,13H),7.24-7.18(m,2H),5.90(d,J=5.8Hz,1H),5.39(d,J=4.0Hz,1H),5.37-5.30(m,1H),5.26(dd,J=10 .9,5.8Hz,1H),5.19(t,J=9.0Hz,1H),5.06(t,J=9.9Hz,1H),4.90-4.76(m,3H),4.68(s,2H),4.58(d,J=10.1Hz,1H),4.47(t,J=11.9Hz,2H), 4.40(d,J=11.3Hz,1H),4.34(dd,J=12.3,2.3Hz,1H),4.29(t,J=6.6Hz,1H),4.26-4.17(m,2H),4.05-3.90(m,4H),3.86(dt,J=12Hz,1H),3. 59(d,J=6.9Hz,2H),3.51(dt,J=9.7,3.0Hz,1H),2.10(s,3H),2.10(s, 3H),2.04(s,3H),2.03(s,3H),2.00(s,3H),1.99(s,3H),1.99(s,3H). 13 C NMR (100MHz, CDCl3) δ170.6,170.5,170.4,170.2,169.9,169.6,169.4,137.8,1 37.7,136.9,128.6,128.5,128.4,128.20,128.17,128.13,128.10,127.9,95.6, 84.0,82.3,81.4,76.39,76.36,75.7,75.3,73.8,73.2,73.1,72.0,71.7,71.1,70.0,69.3,68.4,68.0,62.5,61.4,20.9,20.8,20.7,20.60,20.58,20.57,20.5. Calculate C 53 H 64 NO 23 S(M+H) + HRMS (ESI) of M / z 1114.3590, found 1114.3595.

[0116] 1-S-(2,3,4,6-tetra-O-acetyl-β-D-glucopyranosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-glucopyranosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-galactopyranoside (4f):

[0117] The reaction was carried out according to the general procedure, using donor 1a (46.2 mg, 0.1 mmol) and acceptor 2f (78.3 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A white foam solid compound 4f (101.4 mg, 91% yield, only α, PE: EA = 1: 1, Rf = 0.45) was obtained. [α] D 35 +50.7 (c=0.90, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.38-7.26(m,12H),7.26-7.18(m,3H),5.90(d,J=5.8Hz,1H),5.24(dd,J=10.9,5.8Hz,1H),5.16-5. 08(m,2H),5.05(t,J=9.6Hz,1H),4.94(t,J=8.1Hz,1H),4.92-4.87(m,1H),4.81(d,J=11.0Hz,1H),4.68(s,2H),4.54-4.3 9(m,6H),4.36(dd,J=12.5,4.3Hz,1H),4.26(dd,J=7.6,6.0Hz,1H),4.18(dd,J=10.9,2.9Hz,1H),4.09-3.99(m,3H),3.77 (t,J=9.5Hz,1H),3.67-3.58(m,2H),3.58-3.50(m,2H),2.10(s,3H),2.08(s,3H),2.02(s,3H),2.01(s,9H),1.98(s,3H). 13 C NMR (100 MHz, CDCl3) δ 170.5, 170.24, 170.20, 169.7, 169.5, 169.3, 169.0, 137.9, 137.7, 137.0, 128.53, 128.50, 128.4, 128.2, 128.1, 128.0, 127.89, 127.87, 100.7, 84.1, 83.0, 81.8, 75.9, 75.7, 75.4, 73.6, 73.4, 73.1, 73.0, 72.0, 71.6, 71.2, 71.0, 67.8, 67.4, 61.7, 61.5, 20.8, 20.7, 20.5. Calculated C 53 H 64 NO 23 S(M+H) + HRMS (ESI) of M / z 1114.3590, found 1114.35 84.

[0118] 1-S-(2,3,4,6-Tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-3,4-di-O-benzyl-2-deoxy-2-nitro-6-O-triisopropylsilyl-1-thio-α-D-galactopyranoside (4g):

[0119] The reaction was carried out according to the general procedure, using donor 1b (52.7 mg, 0.1 mmol) and acceptor 2a (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). A colorless oily compound 4g (82.1 mg, yield 92%, α:β=25:1, PE:EA=2:1, Rf=0.45) was obtained. [α] D 35 +45.4 (c=1.45, CHCl3); 1 HNMR (400MHz, CDCl3) δ7.38-7.26(m,10H),5.88(d,J=5.8Hz,1H),5.41(d,J=2.9Hz,1H),5.27(dd,J=10.9,5.8Hz,1H),5.22(t, J=10.0Hz,1H),5.00(dd,J=10.0,3.3Hz,1H),4.83(d,J=10.7Hz,1H),4.75(d,J=11.0Hz,1H),4.75(d,J=11.0Hz,1H),4.70(d,J= 11.0Hz,1H),4.56(d,J=10.7Hz,1H),4.51(d,J=9.9Hz,1H),4.18(dd,J=10.9,2.8Hz,1H),4.13-4.00(m,4H),3.93(t,J=6.7Hz,1 H),3.86(t,J=9.2Hz,1H),3.75(dd,J=9.2,5.3Hz,1H),2.15(s,3H),2.05(s,3H),2.02(s,3H),1.97(s,3H),1.12-1.02(m,21H). 13 C NMR (100 MHz, CDCl3) δ 170.24, 170.15, 170.0, 169.5, 138.2, 137.1, 128.6, 128.4, 128.31, 128.28, 127.9, 127.7, 84.9, 84.5, 83.1, 75.6, 75.5, 74.7, 73.3, 73.2, 72.7, 71.7, 67.9, 67.0, 61.0, 60.2, 20.7, 20.63, 20.62, 20.6, 18.07, 18.05, 11.9. Calculated C43 H 62 NO 15 SSi(M+H) + HRMS (ESI) of M / z 892.3610, found 892.3618.

[0120] 1-S-(2,3,4,6-Tetra-O-acetyl-1-thio-β-D-glucopyranosyl)-3,4-di-O-benzyl-2-deoxy-2-nitro-6-O-triisopropylsilyl-1-thio-α-D-galactopyranoside (4h):

[0121] The reaction was carried out according to the general procedure, using donor 1b (52.7 mg, 0.1 mmol) and acceptor 2b (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). A colorless oily compound 4h (78.5 mg, yield 88%, only α, PE:EA=2:1, Rf=0.45) was obtained. [α] D 35 +69.5 (c=1.04, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.37-7.26(m,10H),5.89(d,J=5.9Hz,1H),5.26(dd,J=10.9,5.8Hz,1H),5.17(t,J=9.3Hz,1H),5.07( t,J=9.7Hz,1H),5.01(t,J=9.6Hz,1H),4.83(d,J=10.7Hz,1H),4.75(d,J=11.0Hz,1H),4.69(d,J=11.0Hz,1H),4.54(t,J=10 .6Hz,2H),4.27(dd,J=12.4,4.5Hz,1H),4.17(dd,J=10.9,2.8Hz,1H),4.10-3.96(m,3H),3.85(t,J=9.2Hz,1H),3.76(dd,J= 9.2,5.4Hz,1H),3.70(ddd,J=9.9,4.3,2.1Hz,1H),2.07(s,3H),2.03(s,3H),2.01(s,3H),1.99(s,3H),1.13-0.98(m,21H). 13C NMR (100 MHz, CDCl3) δ 170.6, 170.1, 169.4, 169.3, 138.2, 137.1, 128.6, 128.4, 128.30, 128.28, 127.8, 127.7, 84.4, 84.1, 82.8, 76.3, 75.7, 75.4, 73.6, 73.3, 73.2, 72.6, 70.9, 67.8, 61.9, 60.2, 20.7, 20.58, 20.55, 20.5, 18.0, 11.9. Calculated C 43 H 62 NO 15 SSi(M+H) + HRMS (ESI) of M / z 892.3610, found 892.3604.

[0122] Compound 6a includes two configurations, α and β. The synthesis method is as follows: the reaction is carried out according to the general procedure, using donor 5a (46.2 mg, 0.1 mmol) and acceptor 2a (43.7 mg, 0.12 mmol). The product is purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). Among them, 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-α-D-pyranoglucoside / β-D-pyranoglucoside / α-D-pyranomannoside (6a-α) is a white oily compound (79.3 mg, yield 96%, α-glu:β-glu:α-man=17:1:6, PE:EA=2:1, Rf=0.3). 1 H NMR(400MHz, Acetone-d6)δ7.43-7.22(m),6.11(d,J=5.8Hz),6.05(d,J=2.4Hz),5.46(dd,J= 4.8,2.6Hz),5.43(dd,J=3.1,1.0Hz),5.39(dd,J=3.2,0.9Hz),5.2-5.12(m),5.07(d,J=9.8H z),4.98-4.92(m),4.85-4.71(m),4.69-4.62(m),4.60-4.53(m),4.35(t,J=8.4Hz),4.32-4. 02(m),3.96-3.79(m),2.12(s),2.11(s,1H),2.04(s),2.01(s),1.98(s),1.94(s),1.92(s). 13C NMR (100MHz, Acetone-d6) δ170.62,170.58,170.5,170.4,170.1,170.0,16 9.9,169.8,139.4,139.17,139.15,138.94,138.90,138.7,138.5,138.2,1 29.2,129.13,129.05,129.01,128.96,128.9,128.70,128.68,128.64,128 .61,128.58,128.51,128.48,128.45,128.42,128.36,128.31,128.29,128 .19,87.20,86.5,84.4,83.3,82.5,79.5,79.3,79.2,78.8,77.7,76.1,75.5,75.30,75.25,75.2,75.0,74.6,74.3,73.9,73.8,73.50,73.48,73.1,73 .0,72.4,72.3,72.2,72.0,71.6,69.3,68.9,68.82,68.77,68.4,68.31,68.30,68.27,68.2,62.3,62.1,62.0,20.7,20.57,20.55,20.52,20.47,20.4. Calculate C 41 H 48 NO 15 S(M+H) + HRMS (ESI) of M / z 826, found 826.2746.

[0123] 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-3,4,6-tri-O-benzyl-2-deoxy-2-nitro-1-thio-β-D-glucopyranoside (6a-β), a colorless oily compound; [α] D 25 +3.5 (c = 0.33, CHCl3); 1H NMR (400MHz, Acetone-d6) δ7.45-7.17(m,15H),5.40(dd,J=2.9,0.9Hz,1H),5.32(d,J=10.3 Hz,1H),5.23-5.09(m,3H),4.89-4.82(m,2H),4.80(d,J=10.1Hz,1H),4.72(d,J=11.0Hz,1H ),4.66(d,J=12.0Hz,1H),4.62-4.51(m,2H),4.36(dd,J=9.7,8.2Hz,1H),4.17-4.12(m,1H) ,4.11-4.01(m,2H),3.91-3.74(m,4H),2.12(s,3H),2.03(s,3H),1.99(s,3H),1.94(s,3H). 13 C NMR (100 MHz, Acetone-d6) δ 170.7, 170.5, 170.2, 170.0, 139.4, 139.1, 138.6, 129.20, 129.16, 128.8, 128.7, 128.71, 128.67, 128.6, 128.4, 90.0, 83.7, 82.0, 80.5, 80.1, 78.4, 76.0, 75.6, 75.2, 73.9, 72.4, 69.3, 68.3, 68.2, 61.9, 27.5, 20.7, 20.63, 20.55, 20.5. Calculated C 41 H 47 NO 15 SK(M+K) + HRMS (ESI) of m / z 864.2304, found 864.2339.

[0124] Compound 6b includes two configurations, α and β. The synthesis method is as follows: the reaction is carried out according to the general procedure, using donor 5b (46.2 mg, 0.1 mmol) and acceptor 2a (43.7 mg, 0.12 mmol). The product is purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). Among them, 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-4-O-benzyl-2-deoxy-2-nitro-3,6,-di-O-tert-butyldimethylsilyl-1-thio-α-D-pyranoglucoside (6b-α) is a colorless oily compound; [α] D 35 +55.1 (c=0.58, CHCl3); 1H NMR (400MHz, Acetone-d6) δ7.44-7.35(m,4H),7.34-7.28(m,1H),5.82(d,J=5.0Hz,1H),5.43( d,J=1.3Hz,1H),5.23-5.14(m,4H),4.80(s,2H),4.47(dd,J=6.6,4.3Hz,1H),4.23-4.18(m,1H ),4.16(t,J=6.4Hz,1H),4.13-4.03(m,4H),3.91(dd,J=11.2,2.7Hz,1H),2.13(s,3H),2.03(s ,3H),1.99(s,3H),1.93(s,3H),0.94(s,9H),0.89(s,9H),0.12(d,J=2.1Hz,6H),0.09(s,6H). 13 C NMR (100 MHz, Acetone-d6) δ 170.7, 170.5, 170.1, 169.9, 139.3, 129.2, 128.50, 128.47, 88.5, 82.2, 77.2, 76.7, 75.4, 75.3, 74.1, 72.4, 71.7, 68.4, 68.1, 62.4, 62.1, 26.3, 26.1, 20.74, 20.66, 20.6, 20.5, 18.9, 18.4, -4.6, -4.9, -5.0, -5.2. Calculated C 39 H 63 NO 15 SSi2Na(M+Na) + HRMS (ESI) of M / z 896.3355, found 896.33 20.

[0125] 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-4-O-benzyl-2-deoxy-2-nitro-3,6,-di-O-tert-butyldimethylsilyl-1-thio-β-D-pyranoside (6b-β), a colorless oily compound; [α] D 25 +1.2 (c = 0.30, CHCl3); 1H NMR (400MHz, Acetone-d6) δ7.44-7.34(m,4H),7.30(td,J=8.5,4.2Hz,1H),5.43(d,J=2.6Hz,1H),5.33(d,J=10.3Hz,1H),5.20 -5.06(m,3H),δ4.88(d,J=11.8Hz,1H),4.84(d,J=11.8Hz,1H),4.56(t,J=9.8Hz,1H),4.45-4.39(m,1H),4.22(t,J=6.7Hz,1H), 4.18-4.12(m,1H),4.07(dd,J=10.9,6.9Hz,1H),4.00(d,J=12.1Hz,1H),3.93(dd,J=11.6,1.2Hz,1H),3.70-3.60(m,2H),2.13 (s,3H),2.04(s,3H),2.01(s,3H),1.93(s,3H),0.93(s,9H),0.87(s,9H),0.14(s,3H),0.10(s,3H),0.04(s,3H),-0.03(s,3H). 13 C NMR (100 MHz, Acetone-d6) δ 170.8, 170.5, 170.2, 170.0, 139.4, 129.1, 128.3, 127.7, 92.3, 82.2, 81.0, 79.9, 78.5, 76.8, 75.0, 75.0, 72.4, 68.1, 68.0, 62.7, 61.7, 26.3, 26.2, 20.7, 20.59, 20.55, 20.5, 18.9, 18.5, -3.8, -4.5, -5.1, -5.4. Calculated C 39 H 64 NO 15 SSi2(M+H) + HRMS (ESI) of M / z 874.3535, found 874.35 52.

[0126] During the synthesis of compound 6b, 1-S-(2,3,4,6-tetra-O-acetyl-1-thio-β-D-pyranosylgalactosyl)-4-O-benzyl-2-deoxy-2-nitro-3,6,-di-O-tert-butyldimethylsilyl-1-thio-α-D-mannoside (6b-pentosan) was also obtained as a colorless oily compound; [a] D 35 -15.3 (c. 0.27, CHCl3); 1H NMR(400MHz, Acetone-d6)δ7.36(d,J=4.4Hz,4H),7.30(td,J=8.2,4.0Hz,1H),5.46-5.41(m,2H),5.17-5.11( m,4H),4.87(d,J=11.2Hz,1H),4.77(d,J=11.4Hz,1H),4.41-4.32(m,2H),4.18(d,J=6.8Hz,1H),4.12(d,J=6.5 Hz,2H),3.99(d,J=11.6Hz,1H),3.93(dd,J=11.7,4.0Hz,1H),3.47(dd,J=9.0,2.3Hz,1H),2.13(s,3H),2.00(s ,3H),1.98(s,3H),1.93(s,3H),0.95(s,9H),0.90(s,9H),0.20(s,3H),0.13(s,3H),0.12(s,3H),0.10(s,3H). 13 C NMR (100 MHz, Acetone-d6) δ 170.7, 170.5, 170.2, 170.1, 139.6, 129.1, 128.3, 128.2, 91.8, 82.3, 81.9, 76.8, 75.6, 75.5, 75.3, 73.8, 72.4, 68.2, 68.1, 63.1, 62.0, 26.4, 26.1, 20.7, 20.64, 20.55, 20.5, 18.9, 18.4, -4.5, -4.65, -4.68, -5.0. Calculated C 39 H 64 NO 15 SSi2(M+H) + HRMS (ESI) of M / z 874.3535, found 874.3540.

[0127] 1-S-(2,3,4,6-Tetra-O-acetyl-1-thio-β-D-galactopyranosyl)-2-deoxy-2-nitro-3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-glucopyranoside (6c):

[0128] The reaction was carried out according to the general procedure, using donor 5c (59.0 mg, 0.1 mmol) and acceptor 2a (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 6c (89.7 mg, yield 94%, only α, PE: EA = 3: 1, Rf = 3.45) was obtained. [a] D 35+75.0 (c.0.55, CHCl3); 1 H NMR (400MHz, CDCl3) δ5.83(d,J=5.6Hz,1H),5.42(d,J=2.7Hz,1H),5.22(t,J=10.0Hz,1H),5. 01(dd,J=10.0,3.3Hz,1H),4.73(dd,J=10.3,5.6Hz,1H),4.51(d,J=10.0Hz,1H),4.44(dd,J= 10.3,7.9Hz,1H),4.12-4.05(m,2H),4.01(dd,J=11.4,2.3Hz,1H),3.95-3.89(m,3H),3.86(d ,J=9.6Hz,1H),2.15(s,3H),2.04(s,6H),1.98(s,3H),1.12-1.03(m,42H),1.00-0.95(m,7H). 13 C NMR (100 MHz, CDCl3) δ 170.2, 170.1, 170.0, 169.4, 87.8, 85.1, 82.0, 74.7, 73.0, 72.1, 71.7, 68.0, 66.9, 61.1, 60.8, 20.6, 20.6, 20.59, 20.57, 18.0, 17.9, 17.6, 17.54, 17.52, 17.27, 17.25, 17.04, 16.98, 12.93, 12.91, 12.5, 12.3, 12.1. Calculated C 41 H 76 NOSSi3(M+H) + HRMS (ESI) of M / z 954.4193, found 954.4187.

[0129] 1-S-(2,3,4,6-Tetra-O-acetyl-1-thio-β-D-pyranoglucopyranosyl)-2-deoxy-2-nitro-3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-pyranoglucopyranoside (6d-α):

[0130] The reaction was carried out according to the general procedure, using donor 5c (59.0 mg, 0.1 mmol) and acceptor 2b (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). A colorless oil compound 6d (90.7 mg, 95% yield, α:β=11:1, PE:EA=3:1, Rf=0.45) was obtained. [a] D 35 +79.3 (c.0.35, CHCl3); 1HNMR (400MHz, CDCl3) δ5.93(d,J=5.8Hz,1H),5.16(t,1H),5.10(t,J=9.5Hz,1H),5.04(t,J=9.4Hz,1H),4.74( dd,J=10.4,5.7Hz,1H),4.53(d,J=9.9Hz,1H),4.42(dd,J=10.4,8.0Hz,1H),4.30(dd,J=12.5,4.2Hz,1H),4.06 (dd,J=12.5,2.2Hz,1H),3.99(m,J=11.7,2.1Hz,2H),3.94-3.88(m,1H),3.84(d,J=9.6Hz,1H),3.69(ddd,J=9. 5,4.0,2.2Hz,1H),2.09(s,3H),2.04(s,3H),2.02(s,3H),1.99(s,3H),1.12-1.03(m,42H),1.00-0.95(m,7H). 13 C NMR (100 MHz, CDCl3) δ 170.6, 170.2, 169.33, 169.25, 87.7, 83.3, 80.9, 76.3, 74.4, 73.8, 73.0, 72.1, 71.1, 67.7, 61.7, 61.0, 20.7, 20.6, 18.00, 17.95, 17.6, 17.53, 17.49, 17.3, 17.2, 17.1, 17.0, 12.91, 12.89, 12.5, 12.3, 12.1. Calculated C 41 H 76 NO 16 SSi(M+H) + HRMS (ESI) of m / z 954.4193, found 954.4192.

[0131] 1-S-(2,3,4,6-Tetra-O-acetyl-1-thio-β-D-pyranosyl mannosyl)-2-deoxy-2-nitro-3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-pyranoglucoside (6e):

[0132] The reaction was carried out according to the general procedure using donor 5c (59.0 mg, 0.1 mmol) and acceptor 2c (43.7 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 6e (92.3 mg, yield 97%, only α, PE: EA = 3: 1, Rf = 0.45) was obtained. [α] D 35+133.5 (c=1.50, CHCl3); 1 H NMR(400MHz, Acetone-d6)δ5.96(d,J=5.8Hz,1H),5.50(d,J=0.9Hz,1H),5.37 (dd,J=3.3,1.3Hz,1H),5.30-5.21(m,2H),5.14(dd,J=10.2,3.4Hz,1H),4.59 (dd,J=10.2,8.2Hz,1H),4.21-4.11(m,5H),4.00-3.89(m,2H),2.13(s,3H),2 .07(s,3H),2.05(s,3H),1.94(s,3H),1.19-1.05(m,42H),1.04-0.98(m,7H). 13 C NMR (100 MHz, Acetone-d6) δ 170.6, 170.34, 170.25, 170.1, 87.9, 80.1, 79.4, 75.7, 74.5, 73.9, 71.2, 70.8, 70.4, 66.4, 63.3, 62.8, 20.7, 20.6, 20.5, 18.34, 18.32, 18.0, 17.82, 17.80, 17.7, 17.6, 17.4, 17.3, 13.7, 13.5, 13.1, 13.0, 12.7. Calculated C 41 H 76 NO 16 SSi3(M+H) + HRMS (ESI) of M / z 954.4193, found 954.4190.

[0133] Compound 6f includes two configurations, α and β. The synthesis method is as follows: the reaction is carried out according to the general procedure, using donor 5c (46.2 mg, 0.1 mmol) and acceptor 2d (43.7 mg, 0.12 mmol). The product is purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). Among them, 1-S-(2-deoxy-2-acetylamino-3,4,6-tri-O-acetyl-1-thio-β-D-pyranoglucopyranosyl)-2-deoxy-2-nitro-3,6-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-pyranoglucopyranoside (6f-α) is a white solid; [α] D 35 +69.5 (c=1.10, CHCl3); 1H NMR (400MHz, CDCl3) δ6.20(d,J=8.1Hz,1H),5.94(d,J=5.3Hz,1H),5.54(t,J=9.8Hz,1H),5.09(d,J=10.2 Hz,1H),5.00(t,J=9.7Hz,1H),4.73(dd,J=10.3,5.6Hz,1H),4.47-4.38(m,1H),4.29(dd,J=12.4,4.6Hz, 1H),4.10-3.96(m,3H),3.88(dd,J=10.9,5.6Hz,1H),3.78(ddd,J=10.0,4.4,2.2Hz,1H),3.70-3.61(m,2 H),2.09(s,3H),2.01(s,3H),2.00(s,3H),1.96(s,3H),1.13-1.03(m,42H),0.97(dd,J=8.9,5.9Hz,7H). 13 C NMR (100 MHz, CDCl3) δ 171.0, 170.7, 170.3, 169.5, 87.5, 82.6, 79.6, 76.3, 74.6, 73.3, 72.6, 72.4, 68.9, 62.9, 62.1, 55.6, 23.3, 20.72, 20.66, 20.6, 18.03, 17.97, 17.7, 17.5, 17.4, 17.3, 17.2, 17.02, 16.96, 12.9, 12.8, 12.4, 12.2, 12.1. Calculated C 41 H 77 N2O 15 SSi3(M+H) + HRMS (ESI) of M / z 953.4353, found 953.4349.

[0134] 1-S-(2-deoxy-2-acetylamino-3,4,6-tri-O-acetyl-1-thio-β-D-pyranoglucopyranoside)-2-deoxy-2-nitro-3,6-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-β-D-pyranoglucopyranoside (6f-β), a white solid; [α] D 35 +26.0 (c=0.22, CHCl3); 1H NMR(400MHz, CDCl3)δ5.49(d,J=9.2Hz,1H),5.15-5.01(m,3H),4.83(d,J=10 .5Hz,1H),4.44(t,J=9.9Hz,1H),4.38-4.31(m,1H),4.26(dd,J=12.4,4.6Hz ,1H),4.19-4.07(m,3H),3.81(dd,J=11.1,6.6Hz,1H),3.65-3.59(m,2H),3. 52-3.46(m,1H),2.10(s,3H),2.02(s,6H),1.93(s,3H),1.15-0.93(m,49H). 13 C NMR (101 MHz, CDCl3) δ 171.1, 170.7, 170.0, 169.2, 89.9, 82.4, 81.9, 78.9, 77.9, 76.2, 73.8, 72.7, 68.1, 63.2, 62.0, 53.0, 23.2, 20.72, 20.66, 20.6, 18.06, 18.05, 17.31, 17.27, 17.13, 17.11, 17.08, 17.07, 17.0, 12.81, 12.76, 12.21, 12.17, 12.0. Calculated C 41 H 76 N2O 15 SSi3K(M+K) + HRMS (ESI) of M / z 991.3911, found 991.3865.

[0135] 1-S-(2,3,4,6-tetra-O-acetyl-α-D-pyranoglucopyranosyl-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-pyranoglucopyranosyl)-2-deoxy-2-nitro-3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-pyranoglucopyranoside (6 g):

[0136] The reaction was carried out according to the general procedure, using donor 5c (59.0 mg, 0.1 mmol) and acceptor 2e (78.3 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A colorless oily compound 6g (121.8 mg, yield 98%, only α, PE: EA = 3: 1, Rf = 0.4) was obtained. [α] D 35 +88.3 (c=1.80, CHCl3); 1H NMR(400MHz,Acetone-d6)δ6.19(d,J)5.8Hz,1H),5.41(d,J3.9Hz,1H),5.39-5.34(m,1H),5.31(dd,J8.7,4.4Hz,1H),5.06(t,J). S9.9Hz,1H),5.00(dd,J10.4,5.8Hz,1H),4.94(d,J4.5Hz,2H),4.86(dd,J10.5,3.9Hz,1H),4.58(dd,J12.3,2.6Hz,1H),4 (dd,J10.3,8.3Hz,1H),4.31(dd,J12.3,3.6Hz,1H),4.24(dd,J12.4,4.3Hz,1H),4.14-4.03(m,6H),4.00(dt,J9.7,3.1Hz,1H). ),3.91(d,J9.5Hz,1H),2.11(s,3H),2.03(s,3H),2.01(s,3H),1.99(s,6H),1.96(s,6H),1.17-1.08(m,42H),1.03-0.98(m,7H). 13 C NMR(100MHz,Acetone-d6)δ170.9,170.7,170.61,170.59,170.2,170.1,169.9.9 6.8,88.4,82.3,80.7,77.1,76.8,74.8,74.4,74.0,72.9,72.8,71.0,70.0,69.5 ,69.1,63.5,62.5,61.8,21.1,20.8,20.7,20.62,20.57,20.5,18.5,18.5,18.02 ,17.99,17.97,17.7,17.63,17.60,17.4,17.3,13.8,13.7,13.2,13.1,12.9.ReferenceC 53 H 92 WHEN 24 SSi3(M+H) + M / z 1242.5038 HRMS(ESI)

[0137] 1-S-(2,3,4,6-tetra-O-acetyl-β-D-pyranose-(1→4)-2,3,6-tri-O-acetyl-1-thio-β-D-pyranose)-2-deoxy-2-nitro-3,4-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-pyrroloside 6h: The reaction was carried out according to the general procedure, using donor 5c (59.0 mg, 0.1 mmol, 0.1 mmol) and acceptor 2f (78.3 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2:MeOH=1:1). A colorless oily compound 6h (118.0 mg, 95% yield, only α, PE:EA=3:1, Rf=0.4) was obtained. [α] D 35 +42.0 (c=1.00, CHCl3); 1 H NMR (400MHz, Acetone-d6) δ6.17(d,J=5.8Hz,1H),5.22(t,J=9.4Hz,1H),5.17(t,J=9.0Hz,1H),5.05(t,J=8.9Hz,1H),5.01(dd,J=8. 4,3.8Hz,1H),4.97(t,J=8.4Hz,1H),4.90-4.80(m,3H),4.54(dd,J=12.2,1.7Hz,1H),4.48(dd,J=10.4,8.2Hz,1H),4.39(dd,J=12.4, 3.9Hz,1H),4.16(dd,J=12.3,4.1Hz,1H),4.14-4.10(m,2H),4.10-4.04(m,2H),4.01(ddd,J=10.0,3.8,2.4Hz,1H),3.96-3.83(m,3H ),2.10(s,3H),2.04(s,3H),2.01(s,3H),2.01(s,3H),1.97(s,3H),1.97(s,3H),1.92(s,3H),1.19-1.06(m,42H),1.04-0.97(m,7H). 13C NMR (100MHz, Acetone-d6) δ170.7,170.3,170.2,169.90,169.89,169.6,101.3, 88.4,82.7,80.9,77.6,76.8,74.9,74.4,74.2,73.6,72.9,72.5,72.4,72.3,68. 8,62.6,62.4,61.9,20.8,20.71,20.65,20.62,20.55,20.5,18.51,18.47,18.02,17.99,17.98,17.7,17.64,17.61,17.41,17.35,13.8,13.7,13.2,13.1,12.9. Calculate C 53 H 92 NO 24 SSi3(M+H) + HRMS (ESI) of m / z 1242.5038, found 1242.5033.

[0138] 1-S-(2-deoxy-2-acetylamino-3,4,6-tri-O-acetyl-1-thio-β-D-galactopyranosyl)-2-deoxy-2-nitro-3,5-O-(tetraisopropyldisiloxane)-6-O-triisopropylsilyl-1-thio-α-D-glucopyranoside (7):

[0139] The reaction was carried out according to the general procedure, using donor 5c (59.0 mg, 0.1 mmol) and acceptor 2g (43.6 mg, 0.12 mmol). The product was purified by size exclusion chromatography (CH2Cl2: MeOH = 1: 1). A white foam solid compound 7 (92.5 mg, yield 97%, α: β = 25: 1, PE: EA = 1: 1, Rf = 0.45) was obtained. [α] D 35 +90.0 (c=0.35, CHCl3); 1HNMR (400MHz, CDCl3) δ6.55(d,J=7.5Hz,1H),6.03(d,J=5.7Hz,1H),5.67(dd,J=11.0,3.2Hz,1H),5.43( d,J=2.8Hz,1H),5.31(d,J=10.1Hz,1H),4.76(dd,J=10.4,5.7Hz,1H),4.44(dd,J=10.4,8.1Hz,1H),4.19 -4.07(m,4H),4.07-4.01(m,1H),3.82(dd,J=10.8,7.5Hz,1H),3.72(td,J=10.5,7.6Hz,1H),3.52(dd,J= 9.5,8.4Hz,1H),2.12(s,3H),2.03(s,3H),1.96(d,J=1.6Hz,6H),1.18-1.02(m,42H),1.00-0.94(m,7H). 13 C NMR (100 MHz, CDCl3) δ 171.2, 170.4, 170.1, 169.8, 87.3, 81.5, 78.3, 75.2, 74.1, 74.0, 72.5, 69.9, 67.4, 63.9, 61.1, 52.5, 23.5, 20.7, 20.6, 18.1, 18.0, 17.6, 17.44, 17.41, 17.3, 17.23, 17.21, 17.00, 16.95, 12.84, 12.82, 12.5, 12.2, 12.1. Calculated C 41 H 77 N2O 15 SSi3(M+H) + HRMS (ESI) of m / z 953.4353, found 953.4353.

[0140] Synthesis of compound 8:

[0141] Compound 7 (162 mg, 0.17 mmol), zinc powder (222 mg, 3.40 mmol) and anhydrous copper sulfate (27.2 mg, 0.17 mmol) were dissolved in THF:H2O (v:v, 10:1, 1.87 ml) and cooled to 0°C, acetic acid (0.28 ml, 3.4 mmol) and acetic anhydride (0.74 ml) were added dropwise. The solution was then stirred at 0°C for 2 hours. The solution was filtered and concentrated in vacuo. Compound 8 (117 mg, 71%) was obtained as a white foam solid after purification by column chromatography (1:1, PE:EA). [α] D 35 +88.3 (c=0.21, CHCl3); 1H NMR (400MHz, CDCl3) δ6.77(d,J=7.1Hz,1H),5.86(d,J=4.8Hz,1H),5.81(dd,J=11.1,3.1Hz, 1H),5.52(d,J=10.0Hz,1H),5.47(d,J=3.0Hz,1H),4.20-4.05(m,5H),3.82(d,J=8.4Hz,1H) ,3.79(d,J=8.3Hz,1H),3.72(td,J=10.5,7.3Hz,1H),3.48(t,J=8.7Hz,1H),3.32(dd,J=10. 4,4.8Hz,1H),2.11(d,J=1.2Hz,6H),2.02(s,3H),1.97(d,J=3.8Hz,6H),1.21-0.96(m,49H). 13 C NMR (100 MHz, CDCl3) δ 171.3, 170.53, 170.45, 170.1, 169.8, 80.1, 79.8, 75.1, 74.2, 73.8, 73.0, 69.9, 67.7, 64.5, 64.4, 61.3, 53.0, 23.6, 20.70, 20.66, 20.6, 19.2, 18.1, 18.0, 17.42, 17.40, 17.3, 17.21, 17.17, 12.9, 12.8, 12.30, 12.28, 12.1. Calculated C 43 H 81 N2O 14 SSi3(M+H) + HRMS (ESI) of m / z 965.4716, found 965.4702.

[0142] Synthesis of compound 9:

[0143] Compound 8 (40 mg, 0.04 mmol) was dissolved in THF: pyridine (v: v, 1: 1, 1 ml) and cooled to 0 ° C. Then, 65.9% HF / Py (0.2 ml) was added dropwise. The reaction was allowed to warm to room temperature and stirred for 1.5 hours. The crude product was purified by flash column chromatography to remove hydrogen fluoride / pyridine. Then, the crude product was dissolved in pyridine (1 ml) and cooled to 0 ° C. Acetic anhydride (18 μl, 0.2 mmol) and 4,4-dimethylaminopyridine (5 mg, 0.04 mmol) were added successively. The reactant was warmed to room temperature and stirred for 2 hours. The reactant was diluted with CH2Cl2 (10 ml), washed with 1M HCl (5 ml), NaHCO3 (saturated aqueous solution) (5 ml), dried with Na2SO4, filtered and concentrated in vacuo. After purification by column chromatography (40: 1, CH2Cl2: MeOH), a colorless oily compound 9 (19 mg, 65%, 2 steps) was obtained. [α] D 35 +50.0 (c=0.35, CH3OH); 1 H NMR (400MHz, CD3OD) δ5.74(d,J=5.1Hz,1H),5.38(d,J=3.2Hz,1H),5.22(dd,J=10.8,9.3Hz ,1H),5.11-5.05(m,2H),4.80(d,J=10.6Hz,1H),4.57(s,1H),4.46(dt,J=10.1,2.6Hz,1H), 4.35(dd,J=12.5,3.0Hz,1H),4.23-4.12(m,3H),4.10-4.00(m,2H),3.68(dd,J=10.9,5.1H z,1H),2.15(s,3H),2.05(s,6H),2.02(d,J=1.3Hz,6H),2.01(s,3H),1.95(d,J=2.3Hz,6H). 13 C NMR (100 MHz, CD3OD) δ 172.29, 172.26, 171.0, 170.8, 170.7, 170.5, 170.3, 170.0, 84.9, 84.3, 74.5, 71.6, 69.0, 68.5, 67.2, 62.1, 61.9, 61.6, 49.5, 21.5, 19.31, 19.25, 19.24, 19.20, 19.15, 19.1, 17.8. Calculated C 28 H 40 N2O 16 S(M+H) + HRMS (ESI) of m / z 693.2177, found 693.2129.

[0144] The above embodiments are examples of the implementation methods of the present invention, and the implementation methods of the present invention are not limited to the above embodiments. Any other changes, modifications, substitutions, combinations, and simplifications that do not deviate from the spirit and principles of the present invention should be equivalent replacement methods and are included in the protection scope of the present invention.

Claims

1. A method for preparing 1,1'-thiotriose, characterized in that: The steps include: The 2-nitroglycoside donor and the glycosylthiol acceptor are dissolved in solvent 1, and then catalyst 1 is added and stirred at 0 to 20° C. for 1 to 2 hours, followed by TLC analysis, concentration under reduced pressure, and purification to obtain a 1,1'-thiotrisaccharide product; The glycosyl thiol acceptor is 2e or 2f, and the structural formula is: The 2-nitroglycoside donor is 1a or 5c, and the structural formula is: The molar ratio of 2-nitroglycoside donor and glycosylthiol acceptor is 1:(1-2); The molar ratio of glycosyl thiol acceptor to catalyst 1 is (10-12):1; Catalyst 1 is compound 3d, and its structural formula is: The prepared 1,1'-thiotriose product is galactose-type 1,1'-2-nitrothiotriose or glucose-type 1,1'-2-nitrothiotriose, and the structure is as follows:

2. The preparation method according to claim 1, characterized in that Solvent 1 is DCM, Tol, CH3CN or THF; the concentration of solvent 1 is 0.1-0.5M.

3. The preparation method according to claim 1, characterized in that: The steps include: The 2-nitroglycoside donor and the glycosylthiol acceptor were dissolved in dry DCM; then the catalyst 3d was added and the reaction was stirred at 0°C for 1.5 hours and monitored by TLC analysis, and finally the reaction mixture was concentrated under reduced pressure. The residue in the reaction process was purified by size exclusion chromatography to obtain the corresponding 1,1'-thiotrisaccharide product.

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