A one-pot relay glycosylation method for synthesizing 1,3-dithiosaccharides

Abstract

The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for one-pot relay glycosylation to synthesize 1,3-dithiosaccharides. The present invention first realizes "one-pot relay glycosylation": directly converting glycosyl thiol, 3-O-acetyl-2-nitro sugar olefin and another thiol acceptor into 1,3-dithio-2-nitro iduronic glycoside. This method has the advantages of good regioselectivity and stereoselectivity, mild reaction conditions, simple operation, good substrate generality and high synthesis efficiency. The present invention also realizes "one-pot relay glycosylation": directly converting glycosyl thiol, 3-O-acetyl-2-nitro glucose olefin and another thiol acceptor into 1,3-dithio-2-nitro mannoside / glucoside. The present invention also uses "one-pot relay glycosylation" to efficiently and stereoselectively synthesize peptidoglycans with 1,3-linkage, 1,4-linkage and 1,6-linkage, providing a new way for the effective synthesis of peptidoglycan fragment analog thio compounds, and having important application prospects.

Description

Technical Field

[0001] The present invention belongs to the technical field of organic synthesis, and particularly relates to a method for synthesizing 1,3-dithiosugars by one-pot relay glycosylation. Background Art

[0002] 2-Amino-2-deoxysugars are important carbohydrate derivatives and widely exist in nature in the form of various glycoconjugates and natural product sugar molecules. The amino sugars present on the cell surface act as glycosyl receptors and specifically and selectively recognize and bind to enzymes, antibodies, lectins, etc., thereby mediating the mutual recognition between antigens and antibodies.

[0003] O-glycosides are the main form of carbohydrate compounds in nature and have many very important biological activities. If the O atom connected to the sugar on the aglycone is replaced by an S atom, it becomes a thioglycoside, and thioglycosides have better acid-base and biological stability. Contrary to the formation of N- or O-glycosidic bonds, due to the high nucleophilicity of the thio group and the vast majority of properties of thioglycosides being similar to those of O-glycosides. Therefore, thioglycosides can be used to replace O-glycosides to synthesize thio-oligosaccharides or glycoproteins with high efficiency and high selectivity.

[0004] 2-Acetamido-2-deoxysugars exist in organisms in the form of glucose or galactose. When preparing 2-amino-2-deoxysugars by chemical synthesis methods, the design of the amino sugar donor and the protection of the amino group are both particularly important. The inventor found through experiments that when using an amino precursor nitro protecting group to synthesize amino glycosides, the introduction of the nitro group can achieve the synthesis of amino glycosides with high efficiency and high stereoselectivity.

[0005] Based on this, the present application first synthesizes 2-nitrothioglycosides through 2-nitro-glycals, and then simultaneously synthesizes 1,3-dithionitro-glycosides by one-pot method, and designs a new method for efficiently synthesizing 1,3-dithio-2-nitro-glycosides based on 3-O-acetyl-2-nitro-glycals, which is easy to realize large-scale batch production and has important application prospects. Summary of the Invention

[0006] The purpose of the present invention is to provide a method for synthesizing 1,3-dithiosugars by one-pot relay glycosylation, which can efficiently synthesize dithioamino glycoside compounds.

[0007] To achieve the above technical purpose, the present invention adopts the following technical solutions:

[0008] A class of 1,3-dithiosugars, the general structural formula of which is shown as follows:

[0009]

[0010] Among them, R is or

[0011] R’ is Ac, TIPS or

[0012] R” is or

[0013] R”’ is Ac.

[0014] Further preferably, is

[0015] Further preferably, R1 is Boc or Bz.

[0016] Specifically, Ac is acetyl, Bn is benzyl, Me is methyl, t Bu is tert-butyl, Fmoc is fluorenylmethoxycarbonyl, All is allyl, Boc is tert-butoxycarbonyl, Bz is benzoyl, TIPS is triisopropylsilyl.

[0017] Furthermore, the present invention also provides a method for synthesizing the 1,3-dithio-glycoside, comprising the following steps:

[0018] (1) Dissolve the 2-nitro-glycene donor and the receptor 1 in solvent 1, add catalyst 1, and react at -40 - 25 °C for 0.5 - 3 h, then distill off solvent 1 under reduced pressure;

[0019] (2) Dissolve the thiol receptor and the product of step (1) in solvent 2, react at 20 - 25 °C for 0.5 - 1 h or 4 - 5 d, distill off solvent 2 under reduced pressure, and purify to obtain the final product.

[0020] Specifically, in step (1), the receptor 1 is a glycosyl thiol receptor or a mercapto serine receptor.

[0021] Specifically, the 2-nitro-glycene donor is 1a, 10g, 10l, and the specific structural formulas are:

[0022]

[0023] The glycosyl thiol receptor is 2a, 2b, 2d, and the specific structural formulas are:

[0024]

[0025] The mercapto serine receptor is 4l, 4i, and the specific structural formulas are:

[0026]

[0027] The thiol receptors are 4a, 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4j, 4k, and the specific structural formula is:

[0028]

[0029] Specifically, the solvent 1 is dichloromethane, toluene or chloroform, preferably dichloromethane; the solvent 2 is toluene, dichloromethane, acetonitrile, tetrahydrofuran, 1,4-dioxane, fluorobenzene or trifluorotoluene, preferably toluene.

[0030] Based on a general inventive concept, when R' is Ac and R" is the 1,3-dithio-glycoside is 1,3-dithio-2-nitro-iduride, and its general structural formula is shown as follows:

[0031]

[0032] Specifically, is or

[0033] Specifically, R is or

[0034] Specifically, the 1,3-dithio-2-nitro-iduride is a compound with the following structure:

[0035]

[0036] Furthermore, the preparation method of the 1,3-dithio-2-nitro-iduride includes the following steps:

[0037] (1) Dissolve the 2-nitro-glycene donor and the receptor 1 in dichloromethane under nitrogen protection at -40 - 25 °C (preferably -20 °C) to obtain a reaction system I; dissolve the catalyst 1 in dichloromethane and add it to the reaction system I. First, react at -40 - 25 °C (preferably -20 °C) for 0.5 - 1 h, and then react at room temperature (20 - 25 °C) for 1 - 1.5 h. Evaporate the solvent under reduced pressure to obtain the intermediate product I;

[0038] (2) Under nitrogen protection, dissolve the intermediate product I obtained in step (1) in dichloromethane at room temperature (20 - 25 °C), add TEA, and react at room temperature (20 - 25 °C) for 1 - 2 h. Evaporate the solvent under reduced pressure to obtain the intermediate product II;

[0039] (3) Dissolve catalyst 2 and catalyst 3 in toluene under nitrogen protection, mix with intermediate II, then add a thiol acceptor to obtain reaction system II. After that, dissolve catalyst 1 in toluene and add it to reaction system II under nitrogen protection. React at room temperature (20 - 25 °C) for 4 - 5 days, distill off toluene under reduced pressure, and purify by silica gel column chromatography to obtain the final product.

[0040] Specifically, in step (1), acceptor 1 is a glycosyl thiol acceptor; the 2-nitro-glycene donor is 1a, the glycosyl thiol acceptors are 2a, 2b, 2d, and the thiol acceptors are 4a, 4b, 4e, 4f, 4g.

[0041] Specifically, the molar ratio of the 2-nitro-glycene donor to TEA is 1:(0.1 - 0.2). Preferably, the molar ratio of the 2-nitro-glycene donor to TEA is 1:0.2.

[0042] Specifically, in step (3), catalyst 2 is 2,6-bis(trifluoromethyl)benzoic acid, and catalyst 3 is tetrabutylammonium iodide; the molar ratio of catalyst 2 to catalyst 3 is (1 - 1.5):1, preferably 1.5:1.

[0043] Specifically, the molar ratio of the 2-nitro-glycene donor to catalyst 2 is 1:(0.4 - 0.6), preferably 1:0.6.

[0044] Based on a general inventive concept, when R” is the 1,3-dithio-glycoside is 1,3-dithio-2-nitro-mannose / glucoside, and its structural general formula is shown as follows:

[0045] or

[0046] Specifically, is

[0047] Specifically, R is or

[0048] Specifically, R’ is TIPS or

[0049] Specifically, the 1,3-dithio-2-nitro-mannose / glucoside is a compound with the following structure:

[0050]

[0051] Furthermore, the preparation method of the 1,3-dithio-2-nitro-mannose / glucoside includes the following steps:

[0052] (1) Dissolve the 2-nitro glycosyl olefin donor and the acceptor 1 in dichloromethane under nitrogen protection at -40 - 25 °C (preferably -40 °C) to obtain reaction system I; dissolve the catalyst 1 in dichloromethane and add it to reaction system I. First, react at -40 °C to -30 °C (preferably -40 °C) for 1 - 2 hours, then raise the temperature to -20 °C to -10 °C (preferably -20 °C) and react for 0.5 - 1 h. Evaporate the solvent under reduced pressure to obtain intermediate product I;

[0053] (2) Dissolve the catalyst 2 and the catalyst 3 in toluene under nitrogen protection, mix them with the intermediate product I, and then add the thiol acceptor to obtain reaction system II. Then dissolve the catalyst 1 in toluene and add it to reaction system II under nitrogen protection. React at room temperature (20 - 25 °C) for 4 - 5 d. Evaporate toluene under reduced pressure and purify by silica gel column chromatography to obtain the final product.

[0054] Specifically, in step (1), the acceptor 1 is a glycosyl thiol acceptor; the 2-nitro glycosyl olefin donors are 10g, 10l, the glycosyl thiol acceptors are 2a, 2b, 2d, and the thiol acceptors are 4e, 4h, 4j, 4k.

[0055] Specifically, in step (2), the catalyst 2 is 2,6-bis(trifluoromethyl)benzoic acid, and the catalyst 3 is tetrabutylammonium iodide; the molar ratio of catalyst 2 to catalyst 3 is (1 - 1.5):1, preferably 1.5:1.

[0056] Specifically, the molar ratio of the 2-nitro glycosyl olefin donor to the catalyst 2 is 1:(0.4 - 0.6), preferably 1:0.6.

[0057] Based on a general inventive concept, when R” is the 1,3-bisthioglycoside is peptidoglycan 1,3-bisthioglucoside, and its structural general formula is shown as follows:

[0058]

[0059] Specifically, R is or

[0060] Specifically, R’ is TIPS or

[0061] Specifically, the peptidoglycan 1,3-bisthioglucoside is a compound with the following structure:

[0062]

[0063] Further, the preparation method of the peptidoglycan 1,3-bisthioglucoside includes the following steps:

[0064] (1) Dissolve the 2-nitro-glycene donor and acceptor 1 in dichloromethane under nitrogen protection in an ice bath (specifically 0 °C) to obtain reaction system I; dissolve catalyst 1 in dichloromethane and add it to reaction system I, and react at room temperature (20 - 25 °C) for 0.5 - 1 h. Evaporate the solvent under reduced pressure to obtain intermediate product I;

[0065] (2) Mix the thiol acceptor with intermediate product I, dissolve it in toluene under nitrogen protection, react at room temperature (20 - 25 °C) for 0.5 - 1 h, evaporate toluene under reduced pressure, and purify by silica gel column chromatography to obtain the final product.

[0066] Specifically, in step (1), acceptor 1 is a mercapto serine receptor; the 2-nitro-glycene donor is 10g, 10l, the mercapto serine receptor is 4l, 4i, and the thiol acceptor is 4a, 4c, 4d, 4f, 4g, 4h, 4k.

[0067] Based on a general inventive concept, in the above synthesis methods of 1,3-bisthiosaccharide glycosides, preparation methods of 1,3-bisthio-2-nitro iduronic glycosides, preparation methods of 1,3-bisthio-2-nitro mannose / glucose glycosides, and preparation methods of peptidoglycan 1,3-bisthio glucose glycosides, catalyst 1 is 4-pyrrolidinylpyridine (PPY), 4-tert-butylpyridine (4- t BuPy), 4-methoxypyridine (4-OMePy), 4-methoxycarbonylpyridine (4-CO2MePy) or 4-trifluoromethylpyridine (4-CF3Py), preferably 4-pyrrolidinylpyridine (PPY);

[0068] The molar ratio of the 2-nitro-glycene donor to acceptor 1 is 1:(1 - 1.2), preferably 1:1.05; the molar ratio of the 2-nitro-glycene donor to catalyst 1 is 1:(0.1 - 0.2), preferably 1:0.1; the molar ratio of the 2-nitro-glycene donor to the thiol acceptor is 1:(1 - 2), preferably 1:2.

[0069] Compared with the prior art, the advantages of the present invention are:

[0070] 1. First, the present invention uses 3 - O - acetyl - 2 - nitrogalactal and glycosyl thiol under the catalysis of 4 - pyrrolidinylpyridine (PPY) to efficiently synthesize 3 - thioglycosyl - 2 - nitro - ido - hex - 2 - enose compounds through C3 Ferrier rearrangement reaction. During the reaction process, 3 - thioglycosyl - 2 - nitro - ido - hex - 2 - enose reacts with another thiol acceptor under the catalysis of PPY to achieve the highly stereoselective synthesis of 1,3 - dithio - 2 - nitro - ido - glycoside. On this basis, the present invention realizes "one - pot relay glycosylation": directly converting glycosyl thiol, 3 - O - acetyl - 2 - nitrogalactal and another thiol acceptor into 1,3 - dithio - 2 - nitro - ido - glycoside. This method has the advantages of good regioselectivity and stereoselectivity, mild reaction conditions, simple operation, good substrate generality and high synthesis efficiency.

[0071] 2. The present invention also uses PPY to catalyze the efficient synthesis of 3 - thioglycosyl - 2 - nitroglucal compounds from 3 - O - acetyl - 2 - nitroglucal and glycosyl thiol through C3 Ferrier rearrangement reaction. During the reaction process, the 3 - thioglycosyl - 2 - nitroglucal compound reacts with another thiol acceptor under the catalysis of PPY to achieve the highly stereoselective synthesis of 1,3 - dithio - 2 - nitro - manno / glucoside according to the nucleophilic ability and steric hindrance of the acceptor. On this basis, the present invention also realizes "one - pot relay glycosylation": directly converting glycosyl thiol, 3 - O - acetyl - 2 - nitroglucal and another thiol acceptor into 1,3 - dithio - 2 - nitro - manno / glucoside. Further, the present invention also uses "one - pot relay glycosylation" to highly stereoselectively synthesize peptidoglycans with 1,3 - linkage, 1,4 - linkage and 1,6 - linkage, providing a new way for the effective synthesis of thio - compounds of peptidoglycan fragment analogues. Detailed implementation manners

[0072] The technical solutions of the present invention are further described in detail through the following specific examples, but the protection scope of the present invention is not limited thereto.

[0073] Abbreviations in the following examples: Ac is acetyl, t Bu is tert - butyl, Fmoc is fluorenylmethyloxycarbonyl, Bn is benzyl, Me is methyl, TIPS is triisopropylsilyl, Bz is benzoyl, All is allyl, PPY is 4 - pyrrolidinylpyridine, Tf is trifluoromethanesulfonate, DMAP is 4,4 - dimethylaminopyridine, DMF is dimethylformamide, TBAN is tetrabutylammonium nitrate, DTBMP is 2,6 - di - tert - butyl - 4 - methylpyridine, DCM is dichloromethane, TEA is triethylamine, Boc is tert - butyloxycarbonyl.

[0074] Example 1 One - pot relay glycosylation for synthesizing 1,3 - dithio - 2 - nitro - ido - glycoside

[0075] According to the method in the literature (Dharuman S, Gupta P, Kancharla P K, et al. Synthesis of 2-Nitroglycals from Glycals using the Tetrabutylammonium Nitrate–trifluoroacetic Anhydride–triethylamine reagent system and base-catalyzed ferrier rearrangement of Acetylated 2-Nitroglycals[J]. The Journal of Organic Chemistry, 2013, 78(17):8442-8450.), the 3-O-acetyl-2-nitrogalactal donor 1a was first synthesized, and then according to the methods in the literature (Floyd N, Vijayakrishnan B, Koeppe J R, et al. Thiyl glycosylation of olefinic proteins: S-linked glycoconjugate synthesis[J]. Angewandte Chemie International Edition, 2009, 48(42):7798-7802.) and the literature (Wu B, Yang X, Yan M. Synthesis and structure–activity relationship study of antimicrobial auranofin against ESKAPE pathogens[J]. Journal of medicinal chemistry, 2019, 62(17):7751-7768.), the glycosyl thiol acceptors 2a, 2b, and 2d were synthesized.

[0076]

[0077] The thiol receptors 4e–h of the present invention were obtained according to the methods in the literature (Pattabiraman V R, McKinnie S M K, Vederas J C. Solid-supported synthesis and biological evaluation of the lantibiotic peptide bis(desmethyl)lacticin 3147A2[J]. Angewandte Chemie International Edition, 2008, 47(49):9472-9475.), the literature (Noel A, Delpech B, Crich D. Highly stereoselective synthesis of primary, secondary, and tertiary α-S-sialosides under Lewis acidic conditions[J]. Organic letters, 2012, 14(16):4138-4141.), the literature (Ge J T, Zhou L, Luo T, et al. A one-pot method for removal of thioacetyl group via desulfurization under ultraviolet light to synthesize deoxyglycosides[J]. Organic letters, 2019, 21(15):5903-5906.) and the literature (Noel A, Delpech B, Crich D. Highly stereoselective synthesis of primary, secondary, and tertiary α-S-sialosides under Lewis acidic conditions[J]. Organic letters, 2012, 14(16):4138-4141.). Compounds 4a-d can be obtained using commonly available commercial reagents.

[0078]

[0079] Finally, the reaction conditions of the present invention were optimized, and the one-pot method was used with a single catalyst of PPY to complete the simultaneous glycosylation at the 1,3 positions of 2-nitrogalactal. The target compounds 5f-5g, 5m-5n, 5q, 5s with high yields, good regioselectivity and stereospecificity were finally obtained, as shown in the following formula.

[0080]

[0081] In this example, 1,3-dithio-ido-glycosides were constructed by one-pot relay glycosylation. The method for preparing the following compounds 5a, 5g, 5l, 5m, 5n, 5q, and 5s was Reaction 1. In Reaction 1, the 2-nitro-glycene donor was 1a, the glycosyl thiol acceptor was 2a, 2b, 2d, and the thiol acceptor was 4a, 4b, 4e, 4f, 4g.

[0082] Reaction 1: Add the 2-nitro-glycene donor and the glycosyl thiol acceptor to a 10 mL round-bottom flask, and dissolve them in 0.8 mL of dry dichloromethane under nitrogen protection at -20 °C. Dissolve 4-pyrrolidinylpyridine in 0.2 mL of dry dichloromethane, and slowly add it dropwise to the reaction system. After continuing the reaction at -20 °C for half an hour, transfer it to room temperature and react for about 1 h. When the 2-nitro-glycene donor reaction is complete detected by TLC, evaporate the solvent under reduced pressure and azeotrope with toluene twice. Change to nitrogen protection, dissolve in 1 mL of dry dichloromethane at room temperature, slowly add TEA dropwise, react at room temperature for about 1 h, when the reaction system is clean detected by TLC, directly evaporate the solvent under reduced pressure and azeotrope with toluene twice. Add 2,6-bis(trifluoromethyl)benzoic acid and tetrabutylammonium iodide, dissolve them in 1 mL of dry toluene under nitrogen protection, add the thiol acceptor, then dissolve PPY in 0.3 mL of dry toluene and add it to the reaction system under nitrogen protection, and react at room temperature (22 °C) for 4.5 d. Detect by TLC, directly evaporate toluene under reduced pressure, and purify by silica gel column chromatography to obtain 1,3-dithio compounds. The specific dosage ratios of each compound and raw materials are as follows:

[0083] Compound 5a

[0084] Compound 1a (32 mg, 0.1 mmol) and 2a (38 mg, 0.105 mmol) reacted under the condition of PPY (1.5 mg, 0.01 mmol). When the reaction was complete detected by TLC, it was treated with TEA (3 μL, 0.02 mmol), then 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol) and tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol) were added. n-Butyl mercaptan 4a (21 μL, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 4.5 d, detected by TLC and purified by column chromatography to obtain a white powdery solid compound 5a (42.3 mg, 0.068 mmol, 68%), [α] D 25 = +41.2 (c 0.85, CHCl3). 11H NMR (400 MHz, CDCl3) δ 6.28 (s, 1H, Ha-1), 5.28 (t, J = 9.3 Hz, 1H, Hb-3), 5.13 - 5.06 (m, 2H, Hb-4, Hb-2), 4.83 (d, J = 10.1 Hz, 1H, Hb-1), 4.78 (s, 1H, Ha-4), 4.72 (t, J = 6.2 Hz, 1H, Ha-5), 4.62 (d, J = 1.7 Hz, 1H, Ha-3), 4.57 (s, 1H, Ha-2), 4.22 - 4.18 (m, 2H, Hb-6), 4.16 (d, J = 6.2 Hz, 2H, Ha-6), 3.87 - 3.80 (m, 1H, Hb-5), 2.76 - 2.60 (m, 2H, S-1), 2.08 (s, 3H, OAc), 2.07 (s, 6H, OAc), 2.04 (s, 3H, OAc), 2.02 (s, 6H, OAc), 1.71 - 1.62 (m, 2H, S-2), 1.50 - 1.36 (m, 2H, S-3), 0.94 (t, J = 7.3 Hz, 3H, S-4). 13 13C NMR (100 MHz, CDCl3) δ 170.7, 170.4, 170.2, 170.1, 169.5, 169.4, 83.4, 83.1, 78.4, 76.5, 73.6, 69.8, 69.1, 68.3, 63.6, 62.9, 62.1, 38.5, 32.1, 31.2, 22.0, 20.7, 20.6, 13.6. HRMS (ESI-TOF) Calculated for C 28 H 41 NO 16 S2[M+K] + 750.1498, found 750.1486。

[0085] Compound 5f

[0086] Compound 1a (32 mg, 0.1 mmol) and 2a (38 mg, 0.105 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and found to be complete. After treatment with TEA (3 μL, 0.02 mmol), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl thiol 4f (96 mg, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC and then purified by column chromatography to obtain colorless oily compound 5f (46.3 mg, 0.042 mmol, 42%), [α] D 25 = +53.3 (c 1.16, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.41 - 7.27 (m, 15H, H-Ar), 6.41 (s, 1H, Ha-1), 5.29 (t, J = 9.3 Hz, 1H, Hb-3), 5.10 (dd, J = 19.1, 9.3 Hz, 2H, Hb-4, Hb-2), 5.00 (d, J = 10.8 Hz, 1H), 4.93 (d, J = 11.0 Hz, 1H), 4.85 - 4.75 (m, 4H, Ha-4), 4.69 - 4.59 (m, 4H, Ha-3), 4.56 (d, J = 3.4 Hz, 1H, Hc-1), 4.54 (s, 1H, Ha-2), 4.20 (d, J = 3.9 Hz, 2H, Hb-6), 4.14 - 4.09 (m, 2H, Ha-6), 4.00 (t, J = 9.2 Hz, 1H, Hc-3), 3.93 - 3.87 (m, 1H, Hc-5), 3.87 - 3.80 (m, 1H, Hb-5), 3.58 - 3.46 (m, 2H, Hc-2, Hc-4), 3.39 (s, 3H, OMe), 3.05 (dd, J = 14.0, 2.6 Hz, 1H, Hc-6), 2.80 (dd, J = 14.0, 5.9 Hz, 1H, Hc-6), 2.07 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.98 (s, 3H, OAc). 1313C NMR(100MHz,CDCl3)δ170.7,170.4,170.3,170.2,169.50,169.47,138.6,137.98,137.95,128.6,128.5,128.2,128.05,128.02,128.0,127.9,127.7,98.0,83.3,83.0,81.8,80.1,79.5,78.6,76.4,75.8,75.2,73.6,73.5,69.8,69.7,69.0,68.2,63.7,62.7,62.1,55.4,38.2,32.8,20.77,20.73,20.72,20.67,20.65.HRMS(ESI-TOF)Calculated for C 52 H 63 NO 21 S2[M+K] + 1140.2966,found 1140.2963。

[0087] Compound 5g

[0088] Compound 1a(32mg,0.1mmol) and 2a(38mg,0.105mmol) were reacted under the condition of PPY(1.5mg,0.01mmol). The reaction was monitored by TLC and found to be complete. Then it was treated with TEA(3μL,0.02mmol), and then 2,6-di-CF3-PhCOOH(15mg,0.06mmol), tetrabutylammonium iodide TBAI(15mg,0.04mmol), glycosyl mercaptan 4g(67mg,0.2mmol) and PPY(1.5mg,0.01mmol) were added. The mixture was dissolved in 1.3mL of dry toluene. After reacting for 6 days, it was monitored by TLC and purified by column chromatography to obtain a white powdery solid compound 5g(51.7mg,0.042mmol,54%), [α] D 25 =+66.7(c 1.15,CHCl3). 11H NMR (400 MHz, CDCl3) δ 6.36 (s, 1H, Ha-1), 5.48 (t, J = 9.7 Hz, 1H, Hc-3), 5.27 (t, J = 9.3 Hz, 1H, Hb-3), 5.10 (dd, J = 19.7, 9.9 Hz, 2H, Hb-4, Hb-2), 5.01 (t, J = 9.6 Hz, 1H, Hc-4), 4.94 (d, J = 3.6 Hz, 1H, Hc-1), 4.89 (dd, J = 10.2, 3.6 Hz, 1H, Hc-2), 4.82 (d, J = 10.3 Hz, 2H, Hb-1, Ha-4), 4.67 (t, J = 6.1 Hz, 1H, Ha-5), 4.62 (s, 1H, Ha-3), 4.58 (s, 1H, Ha-2), 4.22 - 4.12 (m, 4H, Hb-6, Ha-6), 4.07 - 4.00 (m, 1H, Hc-5), 3.88 - 3.78 (m, 1H, Hb-5), 3.45 (s, 3H, OMe), 2.91 (dd, J = 14.2, 2.7 Hz, 1H, Hc-6), 2.69 (dd, J = 14.2, 7.2 Hz, 1H, Hc-6), 2.11 (s, 9H, OAc), 2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.01 (s, 3H, OAc). 13 13C NMR (100 MHz, CDCl3) δ 170.7, 170.6, 170.20, 170.17, 170.1, 169.8, 169.6, 169.5, 96.6, 83.4, 82.6, 78.0, 76.4, 73.5, 71.3, 70.8, 69.9, 69.7, 69.0, 68.3, 68.2, 63.8, 62.8, 62.1, 55.6, 38.3, 32.2, 29.7, 20.79, 20.75, 20.66, 20.65. HRMS (ESI-TOF) Calculated for C 37 H 51 NO 24 S2[M + K] + 996.1874, found 996.1880。

[0089] Compound 5l

[0090] Compound 1a (32 mg, 0.1 mmol) and 2b (38 mg, 0.105 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete. After treatment with TEA (3 μL, 0.02 mmol), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4e (80 mg, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC and purified by column chromatography to obtain a white powdery solid compound 5l (58.2 mg, 0.057 mmol, 57%), [α] D 25 = +34.1 (c 0.83, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H, H-Ar), 7.63 (t, J = 7.9 Hz, 2H, H-Ar), 7.44 - 7.38 (m, 2H, H-Ar), 7.35 - 7.29 (m, 2H, H-Ar), 6.29 (s, 1H, Ha-1), 6.16 (d, J = 8.4 Hz, 1H, NH), 5.46 (d, J = 4.7 Hz, 1H, Hb-4), 5.34 (t, J = 9.9 Hz, 1H, Hb-2), 5.08 (dd, J = 10.0, 3.2 Hz, 1H, Hb-3), 4.81 (s, 1H, Ha-4), 4.77 (s, 1H, Ha-2), 4.69 (d, J = 9.8 Hz, 1H, Hb-1), 4.66 - 4.60 (m, 3H, Ha-3), 4.46 (dd, J = 10.4, 7.4 Hz, 1H), 4.36 (dd, J = 10.5, 6.9 Hz, 1H), 4.28 - 4.17 (m, 4H, Hb-6), 4.11 (dd, J = 11.6, 7.8 Hz, 1H), 4.04 (t, J = 6.4 Hz, 1H, Hb-5), 3.34 (dd, J = 14.4, 5.0 Hz, 1H), 3.12 (dd, J = 14.4, 3.7 Hz, 1H), 2.19 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.50 (s, 9H, t Bu). 1313C NMR (100 MHz, CDCl3) δ 170.7, 170.6, 170.2, 170.03, 169.97, 169.5, 168.9, 155.8, 143.9, 143.7, 141.3, 127.72, 127.69, 127.14, 127.07, 125.2, 120.0, 83.1, 83.0, 82.9, 80.0, 75.1, 71.6, 69.2, 67.2, 67.1, 67.0, 64.6, 63.1, 61.7, 54.3, 47.1, 37.8, 37.3, 28.0, 20.8, 20.7, 20.6, 20.5. HRMS (ESI-TOF) Calculated for C 46 H 56 N2O 20 S2 [M+K] + 1059.2500, found 1059.2502。

[0091] Compound 5m

[0092] Compound 1a (32 mg, 0.1 mmol) and 2b (38 mg, 0.105 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete. After treatment with TEA (3 μL, 0.02 mmol), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl mercaptan 4f (96 mg, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC and purified by column chromatography to obtain colorless oily compound 5m (70.5 mg, 0.064 mmol, 64%), [α] D 25 = +34.1 (c 0.83, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H, H-Ar), 7.63 (t, J = 7.9 Hz, 2H, H-Ar), 7.44 - 7.38 (m, 2H, H-Ar), 7.35 - 7.29 (m, 2H, H-Ar), 6.29 (s, 1H, Ha-1), 6.16 (d, J = 8.4 Hz, 1H, NH), 5.46 (d, J = 4.7 Hz, 1H, Hb-4), 5.34 (t, J = 9.9 Hz, 1H, Hb-2), 5.08 (dd, J = 10.0, 3.2 Hz, 1H, Hb-3), 4.81 (s, 1H, Ha-4), 4.77 (s, 1H, Ha-2), 4.69 (d, J = 9.8 Hz, 1H, Hb-1), 4.66 - 4.60 (m, 3H, Ha-3), 4.46 (dd, J = 10.4, 7.4 Hz, 1H), 4.36 (dd, J = 10.5, 6.9 Hz, 1H), 4.28 - 4.17 (m, 4H, Hb-6), 4.11 (dd, J = 11.6, 7.8 Hz, 1H), 4.04 (t, J = 6.4 Hz, 1H, Hb-5), 3.34 (dd, J = 14.4, 5.0 Hz, 1H), 3.12 (dd, J = 14.4, 3.7 Hz, 1H), 2.19 (s, 3H, OAc), 2.07 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.05 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.01 (s, 3H, OAc), 1.50 (s, 9H, t Bu). 13 13C NMR (100 MHz, CDCl3) δ 170.7, 170.6, 170.2, 170.03, 169.97, 169.5, 168.9, 155.8, 143.9, 143.7, 141.3, 127.72, 127.69, 127.14, 127.07, 125.2, 120.0, 83.1, 83.0, 82.9, 80.0, 75.1, 71.6, 69.2, 67.2, 67.1, 67.0, 64.6, 63.1, 61.7, 54.3, 47.1, 37.8, 37.3, 28.0, 20.8, 20.7, 20.6, 20.5. HRMS (ESI-TOF) Calculated for C 46 H 56 N2O 20 S2 [M+K] + 1059.2500, found 1059.2502。

[0093] Compound 5n

[0094] Compound 1a (32 mg, 0.1 mmol) and 2b (38 mg, 0.105 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and found to be complete. After treatment with TEA (3 μL, 0.02 mmol), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl thiol 4g (67 mg, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 6 days, the reaction was monitored by TLC and purified by column chromatography to obtain a white powdery solid compound 5n (61.3 mg, 0.064 mmol, 64%), [α] D 25 = +87.1 (c 0.7, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 6.38 (s, 1H, Ha-1), 5.52 - 5.43 (m, 2H, Hc-3, Hb-4), 5.35 (t, J = 9.9 Hz, 1H, Hb-2), 5.08 (dd, J = 10.0, 2.9 Hz, 1H, Hb-3), 5.03 (t, J = 9.6 Hz, 1H, Hc-4), 4.97 - 4.88 (m, 2H, Hc-1, Hc-2), 4.84 (s, 1H, Ha-4), 4.74 (s, 1H, Ha-2), 4.70 - 4.59 (m, 3H, Hb-1, Ha-5, Ha-3), 4.22 (d, J = 6.3 Hz, 2H, Hb-6), 4.13 (d, J = 6.0 Hz, 2H, Ha-6), 4.04 (t, J = 6.4 Hz, 2H, Hb-5, Hc-5), 3.45 (s, 3H, OMe), 2.93 (dd, J = 14.2, 2.4 Hz, 1H, Hc-6), 2.69 (dd, J = 14.3, 6.9 Hz, 1H, Hc-6), 2.20 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.09 (s, 6H, 2OAc), 2.06 (s, 6H, 2OAc), 2.01 (s, 6H, 2OAc), 2.00 (s, 3H, OAc). 1313C NMR(100MHz,CDCl3)δ170.58,170.55,170.24,170.20,170.0,169.8,169.4,96.6,82.9,82.5,77.9,75.0,71.6,71.2,70.8,70.0,69.3,68.3,67.2,67.0,64.0,62.8,61.7,55.6,37.9,32.1,20.9,20.8,20.73,20.71,20.69,20.6,20.5.HRMS(ESI-TOF)Calculated for C 37 H 51 NO 24 S2[M+H] + 958.2315,found 958.2324。

[0095] Compound 5q

[0096] Compound 1a(32mg,0.1mmol) and 2d(69mg,0.105mmol) were reacted under the condition of PPY(1.5mg,0.01mmol). The reaction was monitored by TLC and found to be complete. Then it was treated with TEA(3μL,0.02mmol), and then 2,6-di-CF3-PhCOOH(15mg,0.06mmol), tetrabutylammonium iodide TBAI(15mg,0.04mmol), benzyl mercaptan 4b(23μL,0.2mmol) and PPY(1.5mg,0.01mmol) were added and dissolved in 1.3mL of dry toluene. After reacting for 4.5d, it was monitored by TLC and purified by column chromatography to obtain colorless oily compound 5q(52.7mg,0.051mmol,51%), [α] D 25 =+91.1(c 0.75,CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.39 - 7.27 (m, 5H, H - Ar), 6.11 (s, 1H, Ha - 1), 5.41 (d, J = 3.9 Hz, 1H, Hc - 1), 5.39 - 5.31 (m, 2H, Hb - 3, Hc - 3), 5.06 (t, J = 9.9 Hz, 1H, Hc - 4), 4.95 (t, J = 9.6 Hz, 1H, Hb - 2), 4.87 (dd, J = 10.5, 4.0 Hz, 1H, Hc - 2), 4.81 (d, J = 9.8 Hz, 2H, Hb - 1, Ha - 4), 4.74 (t, J = 6.2 Hz, 1H, Ha - 5), 4.63 - 4.54 (m, 2H, Ha - 3, Hb - 6), 4.44 (s, 1H, Ha - 2), 4.27 (dd, J = 12.5, 3.8 Hz, 1H, Hc - 6), 4.20 - 4.12 (m, 3H, Ha - 6, Hb - 6), 4.10 - 3.95 (m, 3H, Hc - 6, Hc - 5, Hb - 4), 3.87 - 3.74 (m, 3H, CH2Ph, Hb - 5), 2.11 (s, 3H, OAc), 2.10 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.04 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.01 (s, 6H, 2OAc). 13 13C NMR (100 MHz, CDCl3) δ 170.64, 170.62, 170.5, 170.2, 170.1, 169.9, 169.8, 169.5, 136.3, 129.1, 128.8, 127.7, 95.6, 83.0, 82.7, 76.9, 76.8, 76.0, 72.5, 70.4, 70.0, 69.3, 69.0, 68.6, 67.9, 63.8, 62.9, 62.6, 61.5, 38.5, 35.5, 20.9, 20.8, 20.8, 20.7, 20.6. HRMS (ESI - TOF) Calculated for C 43 H 55 NO 24 S2[M + K] + 1072.2187, found 1072.2189。

[0097] Compound 5s

[0098] Compound 1a (32 mg, 0.1 mmol) and 2d (69 mg, 0.105 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete. After treatment with TEA (3 μL, 0.02 mmol), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl thiol 4g (67 mg, 0.2 mmol) and PPY (1.5 mg, 0.01 mmol) were dissolved in 1.3 mL of dry toluene. After reacting for 6 days, the reaction was monitored by TLC and the product was purified by column chromatography to obtain a white powdery solid compound 5s (49.8 mg, 0.040 mmol, 40%), [α] D 25 = +87.0 (c 1.2, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 6.38 (s, 1H, Ha-1), 5.48 (t, J = 9.7 Hz, 1H), 5.42 (d, J = 4.0 Hz, 1H, Hd-1), 5.39 - 5.32 (m, 2H, Hd-4), 5.10 - 4.99 (m, 2H), 4.98 - 4.84 (m, 4H), 4.81 (d, J = 10.1 Hz, 2H), 4.65 (t, J = 6.3 Hz, 1H, Ha-5), 4.61 (d, J = 10.3 Hz, 2H, Ha-3), 4.55 (s, 1H), 4.28 (dd, J = 12.4, 3.8 Hz, 1H), 4.21 - 4.12 (m, 3H, Ha-2), 4.10 - 3.97 (m, 4H, Hd-5), 3.83 - 3.76 (m, 1H), 3.44 (s, 3H, OMe), 2.93 (dd, J = 14.3, 2.7 Hz, 1H, Hd-6), 2.68 (dd, J = 14.3, 6.9 Hz, 1H, Hd-6), 2.12 (s, 3H, OAc), 2.11 (s, 3H, OAc), 2.09 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.065 (s, 3H, OAc), 2.055 (s, 6H, 2OAc), 2.04 (s, 3H, OAc), 2.03 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.012 (s, 3H, OAc), 2.010 (s, 3H, OAc). 1313C NMR (100 MHz, CDCl3) δ 170.62, 170.56, 170.5, 170.2, 170.1, 169.9, 169.82, 169.76, 169.5, 96.6, 95.6, 82.9, 82.7, 78.1, 76.9, 75.9, 72.4, 71.2, 70.8, 70.3, 70.03, 69.96, 69.3, 69.0, 68.5, 68.3, 67.9, 63.7, 62.8, 62.5, 61.5, 55.6, 38.2, 32.1, 20.9, 20.8, 20.7, 20.6. HRMS (ESI-TOF) Calculated for C 49 H 67 NO 32 S2[M+NH4] + 1263.3426, found 1263.3434。

[0099] Example 2 One-Pot Relay Glycosylation for the Synthesis of 1,3-Dithio-2-nitromannoside / glucoside

[0100] In this invention, compound S6 is first used to synthesize compound S10, and then 10 g is synthesized. The specific reaction formula is as follows:

[0101]

[0102] The reagents and conditions in the reaction process are: (a) TIPSCl, DMAP, Imidazole, DMF. (79%). (b) TBAN, DTBMP, Tf2O, DCM. (62%).

[0103] Among them, compound S6 is synthesized by the method in the literature (Filice M, Guisan J M, Terreni M, et al. Regioselective monodeprotection of peracetylated carbohydrates [J]. natureprotocols, 2012, 7(10): 1783-1796.). In addition, the synthesis method of compound S10 is:

[0104] Compound S6 (15.7 g, 68.4 mmol), DMAP (8 g, 68.4 mmol) and imidazole (28 g, 410.4 mmol) are dissolved in 40 mL of dry DMF. TIPSCl (59 mL, 273.6 mmol) is slowly added dropwise under ice bath, and then the reaction is carried out at 60 °C for 48 h. TLC is used to detect the completion of the reaction (R f(PE / EA = 3:1), purified by column chromatography (PE / EA = 500:1), to obtain a pale yellow solid compound S10 (21 g, 54.3 mmol, 79%).

[0105] The synthesis method of compound 10 g is as follows:

[0106] Dissolve compound S10 (10 g, 26 mmol), TBAN (15.8 g, 52 mmol) and DTBMP (10.7 g, 52 mmol) in dry dichloromethane (5 mL) at room temperature. Slowly add trifluoromethanesulfonic anhydride (8.7 mL, 52 mmol) dropwise at -70 °C, and continue the reaction for about 10 min. Monitor the reaction by TLC (R f = 0.2, PE / EA = 10:1). Pour the reaction system into a mixed system of 1 M HCl and dichloromethane. Extract with dichloromethane three times, combine the organic phases, wash once with saturated sodium chloride solution, dry over anhydrous sodium sulfate, filter, evaporate the solvent under reduced pressure. Wash the crude product with ethyl acetate, discard the filter residue, concentrate the filtrate under reduced pressure, and purify by silica gel column chromatography (PE / EA = 10:1) to obtain a pale yellow solid compound 10 g, [α] D 25 = -34.9 (c 0.9, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 8.33 (s, 1H, H-1), 5.88 - 5.79 (m, 1H, H-3), 4.69 - 4.57 (m, 1H, H-5), 4.38 - 4.29 (m, 2H, H-6, H-4), 4.13 (dd, J = 12.2, 5.1 Hz, 1H, H-6), 2.11 (s, 3H, OAc), 2.07 (s, 3H, OAc), 1.19 - 1.02 (m, 21H, 3 i Pr). 13 C NMR (100 MHz, CDCl3) δ 170.3, 169.5, 155.1, 128.0, 79.4, 65.2, 64.2, 60.8, 20.7, 17.85, 17.81, 12.0. HRMS (ESI-TOF) Calculated for C 19 H 33 NO8Si [M + H] + 432.2054, found 432.2047.

[0107] The structural formula of compound 10 l is as follows:

[0108]

[0109] Compound 10l was synthesized by the method in the literature (Wu X, Zheng Z, Wang L, et al. Stereoselective Synthesisof 2,3-Diamino-2,3-dideoxyglycosides from 3-O-Acetyl-2-nitroglycals[J]. European Journal of Organic Chemistry, 2022, 2022(26):e202200519.).

[0110] The present invention also synthesized thiol receptors 4j and 4k according to the method in the literature (Abacilar M, Daus F, Haas C, et al. Synthesis and NMRanalysis of 13Cand 15N-labeled long-chain polyamines (LCPAs)[J]. RSC Advances, 2016, 6(96):93343-93348.) and the thiol receptors 4e–i obtained by the aforementioned method.

[0111]

[0112] The present invention also prepared thiol receptor 4l, and compound 4l can be obtained by using commonly available commercial reagents.

[0113] The structural formula of compound 4l is as follows:

[0114]

[0115] Finally, the present invention optimized the reaction conditions, used PPY as the catalyst, and completed the synthesis of 1,3-dithio-glucose / mannoside by a one-pot method. Finally, the target compounds 12g', 12i-12j, 12m, 12o, 12q, 12p' with higher yields and better selectivities were obtained, and the results are shown in the following formula.

[0116]

[0117] In this example, 1,3-dithio-glucose / mannoside was constructed by one-pot relay glycosylation, and the method for preparing the following compounds 12d / 12d', 12g / 12g', 12i / 12i', 12j / 12j', 12m / 12m', 12o / 12o', 12p / 12p', 12q / 12q' was reaction two. In reaction two, the 2-nitrosugar enol donors were 10g and 10l, the glycosyl thiol receptors were 2a, 2b, and 2d, and the thiol receptors were 4e, 4h, 4j, and 4k.

[0118] Reaction 2: Add the 2-nitro glycene donor and the glycosyl mercaptan acceptor into a 10 mL round-bottom flask. Under nitrogen protection, dissolve them in 0.8 mL of dry dichloromethane at -40 °C. Then dissolve the catalyst 4-pyrrolidinylpyridine in 0.2 mL of dry dichloromethane and slowly add it dropwise to the reaction system. After that, continue the reaction at -40 °C for about 2 hours and then slowly raise the temperature to -20 °C. When TLC detects that the nitro glycene donor has completely reacted, transfer the reaction mixture to room temperature. When TLC detects that the reaction system is clean, directly distill off the solvent under reduced pressure and azeotrope with toluene twice. Add 2,6-bis(trifluoromethyl)benzoic acid and tetrabutylammonium iodide, dissolve them in 0.8 mL of dry toluene under nitrogen protection. After adding the mercaptan acceptor, dissolve PPY in 0.2 mL of dry toluene and add it to the reaction system under nitrogen protection. React at 25 °C for 4.5 d. Detect by TLC, directly distill off toluene under reduced pressure, and purify by silica gel column chromatography to obtain the 1,3-dithio compound. The specific amounts and ratios of each compound and raw material are as follows:

[0119] Compound 12d / 12d′

[0120] Compound 10g (43 mg, 0.1 mmol) and 2a (40 mg, 0.11 mmol) react under the condition of PPY (1.5 mg, 0.01 mmol). When TLC detects that the reaction is complete (PE / EA = 2:1, R f = 0.5), then add 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4e (80 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) and dissolve them in 1 mL of dry toluene. After reacting for 4.5 d, detect by TLC (PE / EA = 3:1, R f = 0.27), and purify by column chromatography (PE / EA = 4:1) to obtain a white foamy solid compound 12d / 12d' (80.6 mg, 0.071 mmol, 71%, 12d / 12d'>20:1), 12d[α] D 25 = +11.4 (c 1.0, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H, H-Ar), 7.60 (t, J = 7.4 Hz, 2H, H-Ar), 7.43 - 7.38 (m, 2H, H-Ar), 7.32 (t, J = 7.4 Hz, 2H, H-Ar), 6.15 (d, J = 8.7 Hz, 1H, NH), 5.94 (d, J = 6.9 Hz, 1H, Ha-1), 5.19 - 5.09 (m, 2H, Hb-3, Hb-4), 4.95 - 4.88 (m, 1H, Hb-2), 4.86 (dd, J = 6.8, 3.8 Hz, 1H, Ha-2), 4.67 - 4.61 (m, 1H), 4.42 - 4.35 (m, 5H, Hb-1, Ha-4, Ha-5, Ha-6), 4.28 (dd, J = 12.5, 3.5 Hz, 1H, Hb-6), 4.22 (t, J = 7.0 Hz, 1H), 4.06 (dd, J = 15.7, 5.2 Hz, 3H, Ha-6, Hb-6), 3.79 (s, 1H, Ha-3), 3.66 (d, J = 9.0 Hz, 1H, Hb-5), 3.33 (dd, J = 14.5, 4.8 Hz, 1H), 3.15 (dd, J = 14.5, 3.6 Hz, 1H), 2.11 (s, 3H, OAc), 2.02 (s, 6H, 2OAc), 2.02 (s, 3H, OAc), 1.99 (s, 3H, OAc), 1.47 (s, 9H, t Bu), 1.12 - 1.07 (m, 21H, 3 i Pr). 13 13C NMR (100 MHz, CDCl3) δ 170.72, 170.68, 170.1, 169.4, 169.3, 168.9, 155.9, 143.9, 143.7, 141.3, 127.8, 127.7, 127.2, 125.1, 120.0, 84.5, 82.9, 80.5, 75.9, 74.5, 73.6, 70.3, 67.6, 67.0, 64.3, 61.4, 54.2, 48.7, 47.1, 36.2, 29.7, 28.0, 26.9, 20.73, 20.67, 20.61, 20.58, 18.02, 17.98, 12.2. HRMS (ESI-TOF) Calculated for C 53 H 74 N2O 19 S2Si [M + H] + 1135.4175, found 1135.4170。

[0121] Compound 12g / 12g′

[0122] 10 g (43 mg, 0.1 mmol) of the nitro sugar olefin compound and 2a (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was detected to be complete by TLC (PE / EA = 2:1, R f = 0.5). Then, 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl mercaptan 4h (96 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, TLC detection (PE / EA = 3:1, R f = 0.56) was carried out, and purification by column chromatography (PE / EA = 5:1) gave a colorless oily compound 12 g / 12g' (43.8 mg, 0.037 mmol, 36%, 12 g / 12g' = 1:7). 12g' [α] D 25 = +21.4 (c 0.8, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.40 - 7.26 (m, 14H, H - Ar), 7.24 (s, 1H, H - Ar), 5.34 (d, J = 8.5 Hz, 1H, Ha - 1), 5.17 (t, J = 9.3 Hz, 1H, Hb - 3), 5.07 (t, J = 9.7 Hz, 1H, Hb - 4), 4.99 (t, J = 9.6 Hz, 1H, Hb - 2), 4.92 (d, J = 10.1 Hz, 1H, HCHPh), 4.88 (dd, J = 12.9, 5.0 Hz, 2H, Ha - 2, HCHPh), 4.72 (d, J = 10.1 Hz, 1H, HCHPh), 4.66 (d, J = 12.0 Hz, 1H, HCHPh), 4.62 (d, J = 3.3 Hz, 1H, Hc - 1), 4.61 - 4.53 (m, 2H, CH2Ph), 4.46 (d, J = 9.9 Hz, 1H, Hb - 1), 4.13 (dd, J = 10.9, 2.2 Hz, 2H, Ha - 6, Hb - 6), 4.07 (d, J = 12.8 Hz, 1H, Ha - 3), 4.05 - 3.96 (m, 2H, Ha - 6), 3.92 (d, J = 11.0 Hz, 1H, Hc - 6), 3.87 (dd, J = 10.6, 5.3 Hz, 2H, Ha - 4, Hc - 5), 3.81 - 3.75 (m, 1H, Hc - 3), 3.72 (dd, J = 10.9, 5.2 Hz, 1H, Hc - 6), 3.65 - 3.56 (m, 2H, Ha - 5, Hc - 2), 3.37 (s, 3H), 3.16 (d, J = 9.9 Hz, 1H, Hb - 5), 3.04 (t, J = 11.0 Hz, 1H, Hc - 4), 2.08 (s, 3H, OAc), 2.06 (s, 3H, OAc), 2.02 (s, 3H, OAc), 2.02 (s, 3H, OAc), 1.96 (s, 3H, OAc), 1.12 - 0.99 (m, 21H, 3 i Pr). 1313C NMR (100 MHz, CDCl3) δ 170.7, 170.3, 170.0, 169.4, 169.3, 138.5, 138.3, 128.5, 128.3, 128.2, 128.1, 128.0, 127.7, 127.6, 127.4, 97.9, 87.8, 82.0, 81.6, 80.6, 78.6, 78.3, 76.4, 76.0, 73.7, 73.4, 73.3, 70.7, 70.5, 69.9, 69.3, 67.8, 63.8, 61.4, 55.3, 46.5, 46.1, 29.7, 20.7, 20.6, 18.1, 18.0, 12.7. HRMS (ESI-TOF) Calculated for C 59 H 81 NO 20 S2Si [M+Na] + 1238.4460, found 1238.4472。

[0123] Compound 12i / 12i′

[0124] The nitroglycene compound 10g (43 mg, 0.1 mmol) and 2a (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was complete (PE / EA = 2:1, R f = 0.5). Then 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4j (83 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC (PE / EA = 2:1, R f = 0.2). The product was purified by column chromatography (PE / EA = 2:1) to obtain a white foamy solid compound 12i / 12i' (48.3 mg, 0.042 mmol, 42%, 12i / 12i' > 20:1), 12i[α] D 25 = +14.8 (c 0.6, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H), 7.64 - 7.59 (m, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 5.77 (d, J = 7.1 Hz, 1H), 5.66 (d, J = 5.4 Hz, 1H), 5.15 (t, J = 9.2 Hz, 1H), 5.09 (t, J = 9.6 Hz, 1H), 5.06 - 5.00 (m, 1H), 4.87 (t, J = 9.5 Hz, 1H), 4.84 - 4.79 (m, 1H), 4.55 (d, J = 11.1 Hz, 1H), 4.44 - 4.36 (m, 3H), 4.30 (d, J = 10.1 Hz, 1H), 4.28 - 4.22 (m, 2H), 4.10 - 4.00 (m, 3H), 3.89 (dd, J = 17.2, 5.2 Hz, 2H), 3.76 (d, J = 15.6 Hz, 5H), 3.64 (d, J = 9.4 Hz, 1H), 3.29 (d, J = 3.5 Hz, 2H), 2.16 (s, 3H), 2.09 (s, 3H), 2.05 (s, 3H), 2.01 (s, 3H), 1.99 (s, 3H), 1.10 (t, J = 4.7 Hz, 21H). 13 13C NMR (100 MHz, CDCl3) δ 170.8, 170.7, 170.02, 169.98, 169.7, 169.4, 168.9, 156.5, 143.9, 143.8, 141.3, 127.7, 127.1, 125.2, 120.0, 84.4, 81.0, 75.9, 75.2, 73.4, 70.2, 67.6, 67.2, 63.8, 61.4, 52.8, 52.5, 47.1, 44.1, 35.5, 20.9, 20.7, 20.6, 18.02, 17.98, 12.2. HRMS (ESI-TOF) Calculated for C 52 H 71 N3O 20 S2Si [M + H] + 1150.3920, found 1150.3913。

[0125] Compound 12j / 12j′

[0126] 10 g (43 mg, 0.1 mmol) of the nitro sugar olefin compound and 2b (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete (PE / EA = 2:1, R f = 0.5). Then, 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4e (80 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, TLC detection (PE / EA = 3:1, R f = 0.27) was carried out, and purification by column chromatography (PE / EA = 4:1) gave a white foamy solid compound 12j / 12j' (89.7 mg, 0.079 mmol, 79%, 12j / 12j'> 20:1), and [α] D 25 of 12j = +15.5 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H), 7.63 - 7.58 (m, 2H), 7.41 (td, J = 7.3, 2.4 Hz, 2H), 7.33 (t, J = 7.4 Hz, 2H), 6.14 (d, J = 8.6 Hz, 1H), 5.93 (d, J = 6.5 Hz, 1H), 5.42 (d, J = 2.8 Hz, 1H), 5.09 (t, J = 9.9 Hz, 1H), 4.99 (dd, J = 10.0, 3.2 Hz, 1H), 4.89 - 4.83 (m, 1H), 4.64 (dt, J = 8.4, 4.1 Hz, 1H), 4.43 - 4.35 (m, 4H), 4.23 (t, J = 6.9 Hz, 1H), 4.15 - 4.06 (m, 6H), 3.90 (t, J = 6.8 Hz, 1H), 3.76 (t, J = 3.3 Hz, 1H), 3.33 (dd, J = 14.5, 4.9 Hz, 1H), 3.15 (dd, J = 14.5, 3.6 Hz, 1H), 2.16 (s, 3H), 2.05 (d, J = 0.7 Hz, 3H), 2.04 (s, 3H), 2.03 (s, 3H), 1.98 (s, 3H), 1.47 (s, 9H), 1.09 (t, J = 9.2 Hz, 21H). 1313C NMR (100 MHz, CDCl3) δ 170.7, 170.3, 170.2, 170.0, 169.6, 168.9, 155.9, 143.9, 143.7, 141.3, 127.73, 127.69, 127.2, 125.1, 120.05, 120.03, 82.9, 74.5, 74.3, 71.6, 67.1, 67.0, 66.7, 64.3, 60.5, 60.4, 54.2, 47.1, 36.1, 28.0, 20.73, 20.70, 20.6, 18.04, 17.99, 14.2, 12.2. HRMS (ESI-TOF) Calculated for C 53 H 74 N2O 19 S2Si [M+Na] + 1157.3994, found 1157.3996。

[0127] Compound 12m / 12m′

[0128] The nitroglycene compound 10g (43 mg, 0.1 mmol) and 2b (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete (PE / EA = 2:1, R f = 0.5). Then 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4j (83 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC (PE / EA = 2:1, R f = 0.2). The product was purified by column chromatography (PE / EA = 2:1) to obtain a white foamy solid compound 12m / 12m' (62 mg, 0.054 mmol, 54%, 12m / 12m' > 20:1), 12m [[alpha]] D 25 = +26.3 (c 0.5, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H), 7.63 (d, J = 5.0 Hz, 2H), 7.40 (t, J = 7.4 Hz, 2H), 7.31 (t, J = 7.0 Hz, 2H), 7.14 (d, J = 8.0 Hz, 1H), 5.79 - 5.66 (m, 2H), 5.41 (d, J = 2.8 Hz, 1H), 5.04 (d, J = 9.9 Hz, 2H), 4.98 (dd, J = 9.9, 3.2 Hz, 1H), 4.85 (s, 1H), 4.54 (s, 1H), 4.46 - 4.35 (m, 3H), 4.33 - 4.23 (m, 2H), 4.13 - 4.01 (m, 4H), 3.95 - 3.85 (m, 3H), 3.78 (s, 3H), 3.72 (s, 1H), 3.30 (d, J = 3.4 Hz, 2H), 2.16 (s, 3H), 2.12 (s, 3H), 2.07 (s, 3H), 2.04 (d, J = 6.3 Hz, 3H), 1.97 (s, 3H), 1.14 - 1.06 (m, 21H). 13 13C NMR (100 MHz, CDCl3) δ 171.9, 170.8, 170.3, 170.1, 170.0, 169.94, 169.91, 143.9, 141.3, 127.7, 127.1, 1252, 120.0, 81.9, 81.0, 75.2, 74.4, 74.3, 71.5, 67.2, 66.6, 64.4, 63.9, 63.9, 63.6, 60.6, 52.8, 52.6, 47.1, 35.6, 33.4, 29.7, 26.9, 20.9, 20.71, 20.67, 20.63, 20.56, 18.04, 17.99, 12.3. HRMS (ESI-TOF) Calculated for C 52 H 71 N3O 20 S2Si [M+Na] + 1172.3739, found 1172.3746。

[0129] Compound 12o / 12o′

[0130] Compound 10l (61 mg, 0.1 mmol) and 2a (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol), and the reaction was detected to be complete by TLC (PE / EA = 1:1, R f= 0.5), 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4e (80 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, TLC detection (PE / EA = 1:1, R f = 0.3), purified by column chromatography (PE / EA = 1:1) to obtain a white foamy solid compound 12o / 12o' (68 mg, 0.052 mmol, 52%, 12o / 12o' > 20:1), 12o [α] D 25 = +36.2 (c 0.65, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 7.76 (d, J = 7.5 Hz, 2H), 7.61 (dd, J = 7.4, 2.8 Hz, 2H), 7.40 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 7.4 Hz, 2H), 6.09 (d, J = 8.6 Hz, 1H), 5.79 (d, J = 8.3 Hz, 1H), 5.63 (d, J = 3.8 Hz, 1H), 5.41 (t, J = 9.9 Hz, 1H), 5.19 (t, J = 9.3 Hz, 1H), 5.12 (t, J = 9.6 Hz, 1H), 5.07 (t, J = 10.1 Hz, 1H), 4.94 (t, J = 9.6 Hz, 1H), 4.74 (dd, J = 10.3, 4.0 Hz, 1H), 4.66 (dd, J = 12.5, 7.1 Hz, 2H), 4.46 - 4.40 (m, 2H), 4.34 (dd, J = 16.7, 7.5 Hz, 2H), 4.24 (dd, J = 18.0, 5.3 Hz, 4H), 4.17 (s, 1H), 4.10 (dd, J = 12.1, 7.8 Hz, 2H), 3.93 (t, J = 7.0 Hz, 1H), 3.81 (dd, J = 11.8, 8.2 Hz, 1H), 3.77 - 3.73 (m, 1H), 3.52 (s, 1H), 3.41 (dd, J = 14.5, 4.4 Hz, 1H), 3.15 (dd, J = 14.4, 3.5 Hz, 1H), 2.21 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.04 (s, 6H), 2.02 (s, 3H), 2.01 (s, 3H), 1.49 (s, 9H). 1313C NMR (100 MHz, CDCl3) δ 171.1, 170.7, 170.6, 170.1, 169.5, 169.3, 168.8, 155.9, 143.81, 141.3, 129.4, 127.7, 127.2, 125.1, 120.1, 95.3, 84.3, 84.0, 83.0, 81.3, 76.3, 73.3, 71.6, 71.2, 69.7, 68.2, 67.9, 67.0, 63.6, 63.5, 61.8, 54.2, 54.1, 47.2, 47.1, 36.3, 31.9, 29.7, 28.05, 27.98, 20.8, 20.73, 20.70, 20.66, 20.63, 20.60, 20.56. HRMS (ESI-TOF) Calculated for C 58 H 72 N2O 28 S2 [M + H] + 1309.3791, found 1309.3780。

[0131] Compound 12p / 12p′

[0132] Compound 10l (61 mg, 0.1 mmol) and 2a (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and was found to be complete (PE / EA = 1:1, R f = 0.5). Then 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), glycosyl thiol 4k (80 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC (PE / EA = 1:1, R f = 0.5). The product was purified by column chromatography (PE / EA = 2:1) to obtain a white foamy solid compound 12p / 12p' (57.7 mg, 0.044 mmol, 44%, 12p / 12p' = 1:3.1), 12p [[alpha]] D 25 = +34.1 (c 0.45, CHCl3). 11H NMR (400 MHz, CDCl3) δ 6.16 (d, J = 7.1 Hz, 1H), 6.04 - 5.86 (m, 3H), 5.52 (d, J = 3.8 Hz, 1H), 5.43 (t, J = 9.8 Hz, 1H), 5.32 (dd, J = 6.4, 1.4 Hz, 1H), 5.29 (s, 1H), 5.28 - 5.23 (m, 1H), 5.20 (d, J = 5.2 Hz, 1H), 5.19 - 5.04 (m, 5H), 4.90 (t, J = 9.6 Hz, 1H), 4.78 (dd, J = 10.3, 3.8 Hz, 1H), 4.63 (s, 1H), 4.49 (dd, J = 12.0, 5.6 Hz, 1H), 4.40 - 4.30 (m, 5H), 4.30 - 4.03 (m, 11H), 3.91 (dt, J = 9.4, 6.4 Hz, 1H), 3.76 - 3.70 (m, 1H), 3.70 - 3.61 (m, 2H), 3.57 - 3.53 (m, 1H), 3.53 - 3.41 (m, 2H), 3.34 (d, J = 9.5 Hz, 1H), 2.97 (dd, J = 9.9, 7.1 Hz, 2H), 2.18 (s, 3H), 2.12 (s, 3H), 2.11 (s, 3H), 2.10 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 2.02 (s, 6H), 2.00 (s, 3H), 1.61 - 1.56 (m, 2H), 1.34 - 1.28 (m, 6H), 0.88 (t, J = 6.7 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 170.83, 170.75, 170.7, 170.13, 170.07, 169.5, 169.4, 135.3, 134.58, 134.55, 117.4, 117.3, 117.1, 105.0, 95.1, 84.6, 78.9, 78.6, 77.9, 76.2, 74.2, 74.0, 73.4, 72.5, 71.3, 70.03, 69.96, 69.8, 69.7, 68.6, 68.1, 68.1, 67.8, 63.3461.9, 61.7, 51.0, 45.8, 31.6, 29.8, 29.7, 29.63, 29.59, 29.56, 29.5, 29.4, 29.3, 29.2, 27.2, 25.8, 22.6, 21.0, 20.8, 20.74, 20.70, 20.63, 20.61, 20.59, 20.56, 14.1. HRMS (ESI-TOF) Calculated for C 57 H 83 NO 29S2[M+Na] + 1332.4390, found 1332.4402.

[0133] Compound 12q / 12q′

[0134] Compound 10l (61 mg, 0.1 mmol) and 2b (40 mg, 0.11 mmol) were reacted under the condition of PPY (1.5 mg, 0.01 mmol). The reaction was monitored by TLC and found to be complete (PE / EA = 1:1, R f = 0.5). Then 2,6-di-CF3-PhCOOH (15 mg, 0.06 mmol), tetrabutylammonium iodide TBAI (15 mg, 0.04 mmol), mercapto serine 4e (80 mg, 0.2 mmol) and PPY (3 mg, 0.02 mmol) were dissolved in 1 mL of dry toluene. After reacting for 4.5 d, the reaction was monitored by TLC (PE / EA = 1:1, R f = 0.3). The product was purified by column chromatography (PE / EA = 1:1) to obtain a white foamy solid compound 12q / 12q' (70.2 mg, 0.047 mmol, 61.5%, 12q / 12q'>20:1), 12q[α] D 25 = +45.8 (c 1.0, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 7.77 (d, J = 7.5 Hz, 2H), 7.61 (d, J = 7.2 Hz, 2H), 7.41 (t, J = 7.4 Hz, 2H), 7.33 (t, J = 7.4 Hz, 2H), 6.11 (d, J = 8.6 Hz, 1H), 5.81 (d, J = 8.0 Hz, 1H), 5.49 - 5.39 (m, 3H), 5.08 (dt, J = 14.7, 9.9 Hz, 2H), 5.01 (dd, J = 10.0, 3.2 Hz, 1H), 4.81 (dd, J = 10.3, 3.9 Hz, 1H), 4.66 (dd, J = 8.6, 4.2 Hz, 2H), 4.46 - 4.36 (m, 3H), 4.36 - 4.20 (m, 5H), 4.19 - 4.04 (m, 5H), 3.99 (t, J = 6.3 Hz, 2H), 3.92 - 3.82 (m, 1H), 3.62 (s, 1H), 3.41 (dd, J = 14.4, 4.2 Hz, 1H), 3.16 (dd, J = 14.4, 3.6 Hz, 1H), 2.19 (s, 3H), 2.18 (s, 3H), 2.11 (s, 3H), 2.07 (s, 6H), 2.04 (s, 9H), 1.98 (s, 3H), 1.50 (s, 9H).13 C NMR (100 MHz, CDCl3) δ 170.7, 170.6, 170.4, 170.2, 170.1, 169.9, 169.8, 169.5, 168.8, 155.9, 143.9, 143.8, 141.33, 141.29, 127.72, 127.68, 127.2, 125.1, 125.0, 120.1, 100.0, 95.6, 94.9, 88.9, 84.9, 83.1, 81.0, 78.6, 74.9, 71.4, 71.2, 71.1, 69.6, 68.3, 68.2, 67.0, 66.9, 66.8, 63.7, 61.8, 61.0, 54.1, 47.1, 36.2, 28.0, 20.7, 20.6. HRMS (ESI-TOF) Calculated for C 58 H 72 N2O 28 S2 [M + H] + 1309.3791, found 1309.3795。

[0135] Furthermore, the present invention also uses amino acid receptors 4a, 4c, 4f–4h, 4k and 4-O-TIPS-2-nitroglucal 10g, 10l for glycosylation, and adopts a one-pot relay glycosylation to synthesize peptidoglycan 1,3-dithio-β-D-glucoside 13a', 13b', 13c / 13c', 13d', 13e', 13f', 13g', 13h', 13j', 13i', and the results are shown in the following formula.

[0136]

[0137] In this example, peptidoglycan 1,3-dithio-β-D-glucoside was constructed by one-pot relay glycosylation, and the method for preparing the following compounds 13a / 13a', 13b / 13b', 13c / 13c', 13d / 13d', 13e / 13e', 13f / 13f', 13g / 13g', 13h / 13h', 13i / 13i', 13j / 13j' was reaction three. In reaction three, the 2-nitroglucal donors were 10g, 10l, the mercapto serine receptors were 4l, 4i, and the thiol receptors were 4a, 4c, 4d, 4f, 4g, 4h, 4k.

[0138] Reaction Three: Add the 2-nitro sugar olefin donor and the mercapto serine receptor into a 10 mL round-bottom flask. Under nitrogen protection, dissolve them in 0.8 mL of dry dichloromethane in an ice bath. Then dissolve the catalyst 4-pyrrolidinylpyridine in 0.2 mL of dry dichloromethane and slowly add it dropwise to the reaction system. Transfer it to room temperature and react for about 30 min. When the TLC detection shows that the nitro sugar olefin donor has completely reacted, directly evaporate the solvent under reduced pressure and azeotrope with toluene twice. Add another thiol receptor, change to nitrogen protection, dissolve it in 1 mL of dry toluene at room temperature, and react at room temperature for about 1 h. When the TLC detection shows that the reaction is complete, directly evaporate toluene under reduced pressure and purify it by silica gel column chromatography to obtain the 1,3-dithio peptidoglycan compound. The specific dosages of each compound and raw material are as follows:

[0139] Compound 13a / 13a′

[0140] Nitro sugar olefin donor 10g (43 mg, 0.1 mmol), mercapto serine receptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and n-butyl mercaptan receptor 4a (13 μL, 0.12 mmol). TLC detection shows that the reaction is complete (PE / EA = 5:1, R f = 0.64). Purify it by column chromatography (PE / EA = 8:1) to obtain a colorless oily compound 13a / 13a' (33 mg, 0.047 mmol, 47%, 13a / 13a' = 1:7.3), 13a'[α] D 25 = +15.4 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 5.25 (d, J = 7.9 Hz, 1H), 4.86 (d, J = 9.7 Hz, 1H), 4.54 (dd, J = 18.2, 8.2 Hz, 2H), 4.43 (dd, J = 12.0, 1.9 Hz, 1H), 4.14 (dd, J = 12.0, 5.5 Hz, 1H), 3.79 (s, 3H), 3.74 - 3.62 (m, 2H), 3.30 (dd, J = 10.2, 9.0 Hz, 1H), 3.15 (dd, J = 11.8, 4.4 Hz, 1H), 2.93 (dd, J = 11.9, 5.5 Hz, 1H), 2.74 - 2.62 (m, 2H), 2.07 (s, 3H), 1.64 - 1.54 (m, 2H), 1.45 (s, 9H), 1.43 - 1.34 (m, 2H), 1.12 (ddd, J = 11.2, 9.5, 5.4 Hz, 21H), 0.91 (t, J = 7.3 Hz, 3H). 1313C NMR (100 MHz, CDCl3) δ 170.6, 155.0, 89.8, 82.9, 81.5, 80.3, 69.8, 63.5, 53.5, 52.9, 52.8, 35.6, 31.6, 30.7, 28.3, 26.9, 21.7, 20.8, 18.4, 18.3, 13.8, 13.6. HRMS (ESI-TOF) Calculated for C 30 H 56 N2O 10 S2Si [M+H] + 697.3224, found 697.3226。

[0141] Compound 13b / 13b′

[0142] Nitro-glycal donor 10g (43 mg, 0.1 mmol), mercapto-serine acceptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and cyclopentanethiol acceptor 4c (13 μL, 0.12 mmol), the reaction was monitored by TLC to completion (PE / EA = 5:1, R f = 0.64), purified by column chromatography (PE / EA = 8:1) to give colorless oil compound 13b / 13b' (37 mg, 0.052 mmol, 52%, 13b / 13b' = 1:8.3), 13b' [α] D 25 = +18.9 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 5.26 (d, J = 7.9 Hz, 1H), 4.91 (d, J = 9.8 Hz, 1H), 4.60 - 4.46 (m, 2H), 4.43 (dd, J = 11.9, 1.8 Hz, 1H), 4.15 (dd, J = 11.9, 5.7 Hz, 1H), 3.79 (s, 3H), 3.74 - 3.62 (m, 2H), 3.36 - 3.24 (m, 2H), 3.14 (dd, J = 11.8, 4.5 Hz, 1H), 2.92 (dd, J = 11.9, 5.5 Hz, 1H), 2.07 (s, 3H), 2.04 - 1.93 (m, 2H), 1.73 (s, 2H), 1.65 - 1.50 (m, 4H), 1.45 (s, 9H), 1.22 - 1.06 (m, 21H). 1313C NMR (100 MHz, CDCl3) δ 170.7, 170.5, 155.0, 89.9, 83.1, 81.4, 80.3, 69.9, 63.6, 53.5, 52.9, 52.8, 44.3, 35.5, 33.9, 33.8, 28.3, 26.9, 24.6, 24.5, 20.8, 18.4, 18.3, 18.2, 13.8. HRMS (ESI-TOF) Calculated for C 31 H 56 N2O 10 S2Si [M+Na] + 731.3043, found 731.3044。

[0143] Compound 13c / 13c′

[0144] Nitro sugar olefin donor 10g (43 mg, 0.1 mmol), mercapto serine receptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and adamantane thiol 4d (20 mg, 0.12 mmol). The reaction was monitored by TLC to completion (PE / EA = 5:1, R f = 0.5), and purified by column chromatography (PE / EA = 8:1) to give colorless oily compound 13c / 13c' (33 mg, 0.043 mmol, 43%, 13c / 13c' = 1.1:1), 13c'[α] D 25 = +33.5 (c 0.55, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 5.25 (d, J = 7.7 Hz, 1H), 5.03 (d, J = 9.9 Hz, 1H), 4.55 (d, J = 7.1 Hz, 1H), 4.47 (t, J = 10.2 Hz, 1H), 4.41 (d, J = 10.8 Hz, 1H), 4.11 (dd, J = 11.8, 6.2 Hz, 1H), 3.79 (s, 3H), 3.71 - 3.61 (m, 2H), 3.35 - 3.24 (m, 1H), 3.15 - 3.08 (m, 1H), 2.92 (dd, J = 11.9, 5.6 Hz, 1H), 2.05 (s, 6H), 1.91 (d, J = 12.1 Hz, 3H), 1.82 (d, J = 12.1 Hz, 3H), 1.74 - 1.65 (m, 6H), 1.45 (s, 9H), 1.19 - 1.08 (m, 21H). 1313C NMR (100 MHz, CDCl3) δ 170.7, 170.5, 89.8, 81.1, 80.3, 78.9, 70.0, 63.8, 53.8, 52.9, 47.1, 43.6, 36.0, 35.4, 29.8, 28.3, 26.9, 20.8, 18.4, 18.3, 13.8. HRMS (ESI-TOF) Calculated for C 36 H 62 N2O 10 S2Si [M+H] + 775.3693, found 775.3684。

[0145] Compound 13d / 13d'

[0146] Nitro-glycallyl donor 10g (43 mg, 0.1 mmol), mercapto-serine acceptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4f (58 mg, 0.12 mmol). The reaction was monitored by TLC to completion (PE / EA = 5:1, R f = 0.22), and purified by column chromatography (PE / EA = 3:1) to give colorless oil Compound 13d / 13d' (88 mg, 0.081 mmol, 81%, 13d / 13d' = 1:11), 13d' [α] D 25 = +21.3 (c 1.0, CHCl3). 11H NMR (400 MHz, CDCl3) δ δ 7.39 - 7.26 (m, 14H), 7.26 - 7.23 (m, 1H), 5.25 (d, J = 7.9 Hz, 1H), 4.98 (dd, J = 10.3, 3.7 Hz, 2H), 4.92 (d, J = 11.2 Hz, 1H), 4.79 (d, J = 12.2 Hz, 2H), 4.68 (d, J = 12.2 Hz, 1H), 4.61 - 4.52 (m, 3H), 4.44 (dd, J = 18.0, 7.9 Hz, 1H), 4.37 (dd, J = 11.9, 1.6 Hz, 1H), 4.08 (dd, J = 12.0, 5.3 Hz, 1H), 3.96 (t, J = 9.2 Hz, 1H), 3.83 - 3.74 (m, 4H), 3.69 (t, J = 8.7 Hz, 1H), 3.56 - 3.46 (m, 2H), 3.37 (s, 3H), 3.30 - 3.21 (m, 2H), 3.14 (dd, J = 11.9, 4.4 Hz, 1H), 3.02 (dd, J = 14.0, 1.9 Hz, 1H), 2.94 - 2.85 (m, 1H), 2.68 (dd, J = 14.0, 9.0 Hz, 1H), 2.03 (s, 3H), 1.45 (s, 9H), 1.18 - 1.03 (m, 21H). 13 13C NMR (100 MHz, CDCl3) δ 170.7, 170.6, 155.0, 138.5, 138.1, 128.6, 128.54, 128.49, 128.2, 128.09, 128.06, 127.99, 127.96, 127.85, 127.76, 97.8, 89.9, 83.2, 81.8, 81.1, 80.9, 80.4, 79.9, 75.8, 75.1, 73.3, 71.1, 69.7, 63.5, 55.4, 53.3, 52.8, 35.7, 32.2, 28.3, 20.9, 18.4, 18.3, 13.8. HRMS (ESI-TOF) Calculated for C 54 H 78 N2O 15 S2Si [M + Na] + 1109.4511, found 1109.4506。

[0147] Compound 13e / 13e′

[0148] Nitro sugar olefin donor 10g (43 mg, 0.1 mmol), mercapto serine receptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4g (40 mg, 0.12 mmol). The reaction was monitored by TLC and found to be complete (PE / EA = 5:1, R f = 0.21). Purification by column chromatography (PE / EA = 2:1) gave a colorless oil compound 13e / 13e' (56.5 mg, 0.060 mmol, 60%, 13e / 13e' = 1:4.8), 13e' [α] D 25 = +60.6 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 5.44 (t, J = 9.8 Hz, 1H, Hc-3), 5.26 (d, J = 7.8 Hz, 1H, NH), 5.16 (d, J = 9.7 Hz, 1H, Ha-1), 4.93 (t, J = 4.2 Hz, 1H, Hc-1), 4.84 (dd, J = 15.8, 6.2 Hz, 2H, Hc-2, Hc-4), 4.55 (d, J = 6.3 Hz, 1H, Hb-2), 4.44 (dt, J = 15.2, 9.0 Hz, 2H, Ha-2, Ha-6), 4.15 (dd, J = 12.0, 5.8 Hz, 1H, Ha-6), 3.93 (td, J = 10.1, 2.1 Hz, 1H, Hc-5), 3.82 - 3.75 (m, 3H, Me), 3.73 (d, J = 8.5 Hz, 1H, Ha-4), 3.70 - 3.64 (m, 1H, Ha-5), 3.40 (s, 3H, Me), 3.32 (t, J = 9.3 Hz, 1H, Ha-3), 3.15 (dd, J = 11.7, 3.9 Hz, 1H, Hb-1), 2.94 - 2.88 (m, 1H, Hb-1), 2.81 (dd, J = 14.6, 10.1 Hz, 1H, Hc-6), 2.71 (dd, J = 14.7, 2.0 Hz, 1H, Hc-6), 2.12 (s, 3H, OAc), 2.08 (s, 3H, OAc), 2.04 (s, 3H, OAc), 2.00 (s, 3H, OAc), 1.45 (s, 9H, t Bu), 1.22 - 1.08 (m, 21H, 3 i Pr). 1313C NMR (100 MHz, CDCl3) δ 170.64, 170.61, 170.2, 170.1, 170.0, 169.84, 169.79, 155.0, 96.4, 89.8, 83.0, 81.3, 80.3, 72.2, 70.9, 70.0, 69.9, 69.8, 63.5, 55.6, 53.2, 52.8, 35.6, 31.5, 28.3, 20.8, 20.73, 20.66, 18.4, 18.3, 18.2, 18.1, 13.7. HRMS (ESI-TOF) Calculated for C 39 H 66 N2O 18 S2Si [M+NH4] + 960.3865, found 960.3867。

[0149] Compound 13f / 13f′

[0150] Nitro-glycofuranosyl donor 10g (43 mg, 0.1 mmol), mercapto-serine acceptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4h (58 mg, 0.12 mmol). The reaction was monitored by TLC to completion (PE / EA = 5:1, R f = 0.22), and purified by column chromatography (PE / EA = 3:1) to afford colorless oil compound 13f / 13f' (52.2 mg, 0.048 mmol, 48%, 13f / 13f' = 1:1.7). The characterization of 13f / 13f' = 1:1.7 [α] D 25 = +31.4 (c 1.0, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.40 - 7.26 (m, 45.5H), 6.14 (d, J = 3.2 Hz, 1H), 5.25 (d, J = 7.8 Hz, 1H), 5.19 (d, J = 7.1 Hz, 1.7H), 5.10 (d, J = 9.8 Hz, 1H), 4.99 (d, J = 10.9 Hz, 1H), 4.91 (dd, J = 9.6, 4.4 Hz, 2H), 4.87 (d, J = 10.6 Hz, 1.7H), 4.80 (d, J = 10.7 Hz, 1.7H), 4.75 (d, J = 12.1 Hz, 3H), 4.68 - 4.60 (m, 7H), 4.60 - 4.51 (m, 8H), 4.47 (dd, J = 16.8, 6.6 Hz, 3.7H), 4.38 (t, J = 6.8 Hz, 1H), 4.31 - 4.22 (m, 3H), 4.11 (dd, J = 11.8, 5.8 Hz, 1.7H), 3.99 (dd, J = 12.0, 5.0 Hz, 2H), 3.94 (d, J = 4.0 Hz, 1H), 3.93 - 3.87 (m, 2H), 3.83 (d, J = 11.7 Hz, 5.1H), 3.79 - 3.75 (m, 5H), 3.70 (d, J = 5.3 Hz, 5H), 3.63 (t, J = 8.7 Hz, 2H), 3.56 - 3.50 (m, 2.7H), 3.37 (dd, J = 8.7, 4.1 Hz, 8.1H), 3.22 (d, J = 6.4 Hz, 1H), 3.17 (t, J = 10.9 Hz, 2H), 3.14 - 3.07 (m, 3H), 3.04 (d, J = 10.4 Hz, 1.7H), 2.85 (s, 2.7H), 1.98 (s, 5.1H), 1.93 (s, 4H), 1.45 (s, 24.3H), 1.18 - 1.05 (m, 56.7H). 1313C NMR (100 MHz, CDCl3) δ 171.0, 170.7, 170.6, 170.5, 155.0, 138.7, 138.4, 138.14, 138.06, 138.0, 128.52, 128.47, 128.41, 128.39, 128.24, 128.19, 128.1, 128.0, 127.9, 127.83, 127.77, 127.72, 127.67, 127.65, 127.63, 127.53, 127.47, 98.4, 98.2, 89.62, 81.3, 81.1, 80.9, 80.8, 80.4, 77.8, 76.1, 75.7, 74.4, 73.5, 73.33, 73.29, 70.8, 70.1, 70.0, 69.7, 69.5, 69.3, 65.6, 63.8, 63.4, 55.4, 53.4, 52.9, 52.9, 50.8, 47.8, 47.1, 37.3, 35.5, 30.6, 29.7, 28.3, 20.7, 18.4, 18.3, 18.3, 18.2, 17.98, 17.96, 13.7, 13.1, 12.2. HRMS (ESI-TOF) Calculated for C 54 H 78 N2O 15 S2Si [M+Na] + 1109.4511, found 1109.4518。

[0151] Compound 13g / 13g′

[0152] Nitro sugar olefin donor 10g (43 mg, 0.1 mmol), mercapto serine acceptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4k (48 mg, 0.12 mmol), TLC detected that the reaction was complete (PE / EA = 5:1, R f = 0.67), column chromatography purification (PE / EA = 3:1) gave colorless oily compound 13g / 13g' (51 mg, 0.051 mmol, 51%, 13g / 13g' = 1:2.4), 13g' [α] D 25 = +29.3 (c 0.35, CHCl3). 11H NMR (400 MHz, CDCl3) δ 6.11 (s, 1H), 6.02 - 5.85 (m, 3H), 5.33 - 5.24 (m, 3H), 5.23 - 5.15 (m, 3H), 5.10 (d, J = 10.5 Hz, 1H), 4.91 (s, 1H), 4.59 - 4.47 (m, 2H), 4.46 - 4.27 (m, 4H), 4.23 (d, J = 7.1 Hz, 1H), 4.20 - 3.96 (m, 5H), 3.89 (dt, J = 13.3, 6.5 Hz, 1H), 3.78 (s, 3H), 3.68 (ddd, J = 18.3, 14.4, 8.1 Hz, 3H), 3.48 (dt, J = 16.3, 8.5 Hz, 2H), 3.37 - 3.22 (m, 2H), 3.21 - 3.10 (m, 2H), 2.99 - 2.85 (m, 2H), 2.06 (d, J = 2.1 Hz, 3H), 1.68 (s, 2H), 1.59 (s, 2H), 1.45 (d, J = 2.8 Hz, 9H), 1.32 (d, J = 27.7 Hz, 6H), 1.18 - 1.03 (m, 21H), 0.88 (t, J = 5.8 Hz, 3H). 13 13C NMR (100 MHz, CDCl3) δ 186.2, 170.8, 170.7, 170.65, 170.55, 135.0, 134.9, 134.7, 134.6, 134.6, 134.3, 134.2, 117.4, 117.4, 117.3, 117.19, 117.15, 117.1, 116.6, 105.2, 104.8, 82.7, 82.7, 81.0, 80.9, 80.7, 79.4, 77.8, 77.3, 77.2, 77.0, 76.7, 75.4, 74.2, 74.0, 73.8, 73.6, 73.0, 72.5, 70.0, 69.0, 68.6, 52.8, 37.5, 31.6, 29.7, 29.6, 29.3, 28.3, 25.8, 25.7, 24.8, 22.7, 22.6, 20.9, 20.8, 18.4, 18.29, 18.27, 18.2, 18.0, 17.9, 14.0, 13.8, 13.3, 12.2. HRMS (ESI-TOF) Calculated for C 47 H 82 N2O 15 S2Si [M+Na] + 1029.4824, found 1029.4819。

[0153] Compound 13h / 13h′

[0154] Nitro sugar olefin donor 10l (61 mg, 0.1 mmol), mercapto serine receptor 4l (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4f (58 mg, 0.12 mmol). The reaction was monitored by TLC to completion (PE / EA = 1:1, R f = 0.46). Purification by column chromatography (PE / EA = 3:1) gave a colorless oily compound 13h / 13h' (72 mg, 0.057 mmol, 57%, 13h / 13h' = 1:10), 13h' [α] D 25 = +54.0 (c 1.0, CHCl3). 1 1H NMR (400 MHz, CDCl3) δ 7.40 - 7.27 (m, 14H), 7.26 - 7.24 (m, 1H), 5.48 - 5.34 (m, 3H), 5.09 (t, J = 9.7 Hz, 1H), 5.00 (dd, J = 10.1, 6.1 Hz, 2H), 4.92 (dd, J = 10.9, 5.3 Hz, 2H), 4.79 (dd, J = 11.5, 4.2 Hz, 2H), 4.70 (d, J = 12.1 Hz, 1H), 4.64 (d, J = 3.2 Hz, 1H), 4.57 (d, J = 11.3 Hz, 1H), 4.44 (dd, J = 20.8, 10.3 Hz, 3H), 4.27 (dd, J = 12.9, 4.2 Hz, 1H), 4.18 - 4.05 (m, 3H), 3.97 (t, J = 9.2 Hz, 1H), 3.84 - 3.76 (m, 4H), 3.70 - 3.63 (m, 1H), 3.61 (d, J = 5.5 Hz, 1H), 3.54 - 3.44 (m, 2H), 3.39 (s, 3H), 3.26 (t, J = 9.3 Hz, 1H), 3.14 (dd, J = 13.0, 5.2 Hz, 1H), 3.04 - 2.93 (m, 2H), 2.71 (dd, J = 14.1, 8.9 Hz, 1H), 2.09 (s, 3H), 2.07 (s, 3H), 2.06 (s, 3H), 2.04 (s, 3H), 2.02 (s, 3H), 1.46 (s, 9H). 1313C NMR (100 MHz, CDCl3) δ 170.61, 170.57, 170.5, 170.0, 169.4, 155.0, 138.5, 138.1, 128.6, 128.52, 128.47, 128.4, 128.2, 128.1, 128.01, 127.95, 127.9, 127.7, 98.0, 97.7, 97.5, 87.7, 82.9, 81.8, 80.9, 80.5, 80.0, 78.8, 75.8, 75.2, 73.2, 71.4, 70.1, 68.7, 68.2, 63.5, 61.7, 55.4, 53.1, 53.0, 49.6, 32.7, 32.1, 29.7, 28.3, 26.9, 21.0, 20.8, 20.7, 20.6. HRMS (ESI-TOF) Calculated for C 59 H 76 N2O 24 S2 [M + H] + 1261.4308, found 1261.4312。

[0155] Compound 13i / 13i′

[0156] Nitro sugar olefin donor 10l (61 mg, 0.1 mmol), mercapto serine receptor 4i (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4f (58 mg, 0.12 mmol). The reaction was monitored by TLC and was complete (PE / EA = 1:1, R f = 0.46). Purification by column chromatography (PE / EA = 3:1) gave colorless oily compound 13i / 13i' (98.7 mg, 0.078 mmol, 78%, 13i / 13i' = 1:8.3), 13i' [α] D 25 = +36.6 (c 1.0, CHCl3). 11H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 7.4 Hz, 2H), 7.53 (t, J = 7.3 Hz, 1H), 7.45 (t, J = 7.4 Hz, 2H), 7.40 - 7.27 (m, 14H), 7.25 (s, 1H), 7.06 (d, J = 6.5 Hz, 1H), 5.39 (t, J = 14.4, 7.3 Hz, 2H), 5.06 (t, J = 9.4 Hz, 1H), 4.99 (d, J = 10.8 Hz, 2H), 4.92 (d, J = 11.1 Hz, 2H), 4.85 (dt, J = 9.2, 4.5 Hz, 1H), 4.78 (dd, J = 11.5, 4.2 Hz, 2H), 4.69 (d, J = 12.1 Hz, 1H), 4.63 (d, J = 2.6 Hz, 1H), 4.56 (d, J = 11.2 Hz, 1H), 4.48 (d, J = 12.2 Hz, 1H), 4.40 (t, J = 10.2 Hz, 1H), 4.26 (d, J = 11.0 Hz, 1H), 4.20 (d, J = 8.9 Hz, 1H), 4.12 (s, 1H), 4.07 (d, J = 12.3 Hz, 1H), 3.96 (t, J = 9.2 Hz, 1H), 3.83 (s, 3H), 3.78 (d, J = 7.9 Hz, 1H), 3.69 (t, J = 8.5 Hz, 1H), 3.61 (s, 1H), 3.54 - 3.46 (m, 2H), 3.37 (s, 3H), 3.29 - 3.17 (m, 3H), 2.99 (d, J = 12.7 Hz, 1H), 2.68 (dd, J = 14.2, 8.9 Hz, 1H), 2.10 (s, 3H), 2.07 (s, 3H), 2.02 (s, 3H), 2.02 (s, 3H), 1.99 (s, 3H). 13 13C NMR (100 MHz, CDCl3) δ 170.9, 170.6, 170.4, 170.1, 169.4, 167.2, 138.5, 138.08, 138.06, 133.3, 132.0, 128.59, 128.56, 128.51, 128.46, 128.1, 128.01, 127.95, 127.9, 127.7, 127.4, 97.8, 97.7, 87.9, 83.2, 81.8, 80.9, 80.0, 78.9, 75.7, 75.2, 73.2, 71.4, 70.5, 69.0, 68.8, 68.1, 63.3, 61.8, 55.4, 53.1, 52.4, 50.2, 32.8, 31.9, 21.1, 20.8, 20.7, 20.62, 20.56. HRMS (ESI-TOF) Calculated for C 61H 72 N2O 23 S2[M+Na] + 1287.3865, found 1287.3868。

[0157] Compound 13j / 13j′

[0158] Nitro-glycallyl donor 10g (43 mg, 0.1 mmol), mercapto-serine acceptor 4i (26 mg, 0.11 mmol), PPY (3 mg, 0.02 mmol) and glycosyl thiol 4f (58 mg, 0.12 mmol). The reaction was monitored by TLC to completion (PE / EA = 3:1, R f = 0.48), and purified by column chromatography (PE / EA = 4:1) to give colorless oil Compound 13j / 13j' (70 mg, 0.064 mmol, 64%, 13j / 13j' = 1:9), 13j'[α] D 25 = +15.4 (c 0.45, CHCl3). 1 H NMR (400 MHz, CDCl3) δ 7.83 (d, J = 7.3 Hz, 2H), 7.52 (d, J = 7.3 Hz, 1H), 7.45 (t, J = 7.4 Hz, 2H), 7.40 - 7.26 (m, 14H), 7.25 (s, 1H), 6.88 (d, J = 6.8 Hz, 1H), 5.05 - 5.00 (m, 1H), 4.97 (t, J = 10.7 Hz, 2H), 4.92 (d, J = 11.2 Hz, 1H), 4.78 (d, J = 12.6 Hz, 2H), 4.67 (d, J = 12.2 Hz, 1H), 4.60 - 4.54 (m, 2H), 4.43 (t, J = 10.2 Hz, 1H), 4.37 (d, J = 10.2 Hz, 1H), 4.05 (dd, J = 12.1, 5.2 Hz, 1H), 3.96 (t, J = 9.2 Hz, 1H), 3.85 (s, 3H), 3.78 (s, 1H), 3.64 (t, J = 8.9 Hz, 1H), 3.53 - 3.45 (m, 3H), 3.37 (s, 3H), 3.24 (dd, J = 21.4, 9.7 Hz, 2H), 3.05 - 2.94 (m, 2H), 2.72 - 2.62 (m, 1H), 2.02 (s, 3H), 1.17 - 0.90 (m, 21H). 1313C NMR (100 MHz, CDCl3) δ 170.6, 166.7, 138.6, 138.1, 133.2, 132.1, 128.64, 128.55, 128.51, 128.46, 128.1, 128.02, 127.96, 127.8, 127.7, 127.2, 97.8, 90.2, 83.2, 81.8, 81.2, 80.9, 80.0, 75.8, 75.1, 73.3, 71.1, 69.8, 63.4, 55.4, 53.2, 52.0, 35.5, 32.2, 20.8, 18.3, 18.2, 13.8. HRMS (ESI-TOF) Calculated for C 56 H 74 N2O 14 S2Si [M+H] + 1091.4429, found 1091.4434。

Claims

1. A method for preparing 1,3 - dithio - 2 - nitro - iduronic acid glycoside, characterized in that, It includes the following steps: (1) Dissolve 2-nitro-glycofuranose donor and acceptor 1 in dichloromethane under nitrogen protection at -40 - 25 °C to obtain reaction system I; dissolve catalyst 1 in dichloromethane and add it to reaction system I. React at -40 - 25 °C for 0.5 - 1 h first, and then react at room temperature for 1 - 1.5 h. Evaporate the solvent under reduced pressure to obtain intermediate I; (2) Under nitrogen protection, add intermediate I obtained in step (1) to dichloromethane for dissolution at room temperature, add TEA, react at room temperature for 1 - 2 h, evaporate the solvent under reduced pressure to obtain intermediate II; (3) Dissolve catalyst 2 and catalyst 3 in toluene under nitrogen protection, mix with intermediate II, then add thiol acceptor to obtain reaction system II. Then dissolve catalyst 1 in toluene and add it to reaction system II under nitrogen protection. React at room temperature for 4 - 5 d, evaporate toluene under reduced pressure, and purify by silica gel column chromatography to obtain the final product; In step (1), the receptor 1 is a glycosyl thiol receptor; the 2-nitro-glycene donor is The glycosyl thiol receptor is The thiol receptor is The molar ratio of 2-nitro-glycofuranose donor to TEA is 1:(0.1 - 0.2); In step (3), catalyst 2 is 2,6-bis(trifluoromethyl)benzoic acid, and catalyst 3 is tetrabutylammonium iodide; the molar ratio of catalyst 2 to catalyst 3 is (1 - 1.5):1; The molar ratio of 2-nitro-glycofuranose donor to catalyst 2 is 1:(0.4 - 0.6); The 1,3-dithio-2-nitro-iduronic glycoside is a compound with the following structure: In the preparation method of the 1,3-dithio-2-nitro-iduronic glycoside, catalyst 1 is 4-pyrrolidinopyridine; The molar ratio of 2-nitro-glycofuranose donor to acceptor 1 is 1:(1 - 1.2); the molar ratio of 2-nitro-glycofuranose donor to catalyst 1 is 1:(0.1 - 0.2); the molar ratio of 2-nitro-glycofuranose donor to thiol acceptor is 1:(1 - 2).

2. A method for preparing 1,3-dithio-2-nitromannoside / glucoside, characterized in that, It includes the following steps: (1) Dissolve 2-nitro-glycofuranose donor and acceptor 1 in dichloromethane under nitrogen protection at -40 - 25 °C to obtain reaction system I; dissolve catalyst 1 in dichloromethane and add it to reaction system I. React at -40 °C - -30 °C for 1 - 2 h first and then raise the temperature to -20 °C - -10 °C to react for 0.5 - 1 h. Evaporate the solvent under reduced pressure to obtain intermediate I; (2) Dissolve catalyst 2 and catalyst 3 in toluene under nitrogen protection, mix with intermediate I, then add thiol acceptor to obtain reaction system II. Then dissolve catalyst 1 in toluene and add it to reaction system II under nitrogen protection. React at room temperature for 4 - 5 d, evaporate toluene under reduced pressure, and purify by silica gel column chromatography to obtain the final product; In step (1), the acceptor 1 is a glycosyl thiol receptor; the 2-nitro-glycene donor is The glycosyl thiol receptor is The thiol receptor is In step (2), catalyst 2 is 2,6-bis(trifluoromethyl)benzoic acid, and catalyst 3 is tetrabutylammonium iodide; the molar ratio of catalyst 2 to catalyst 3 is (1 - 1.5):1; The molar ratio of 2-nitro-glycofuranose donor to catalyst 2 is 1:(0.4 - 0.6); The 1,3-dithio-2-nitro-mannose / glucoside is a compound with the following structure: In the preparation method of the 1,3-dithio-2-nitro-mannose / glucoside, catalyst 1 is 4-pyrrolidinopyridine; The molar ratio of the 2-nitro-glycofuranose donor to the acceptor 1 is 1:(1 - 1.2); the molar ratio of the 2-nitro-glycofuranose donor to the catalyst 1 is 1:(0.1 - 0.2); the molar ratio of the 2-nitro-glycofuranose donor to the thiol acceptor is 1:(1 - 2).

3. A method for preparing peptidoglycan 1,3-dithio-β-D-glucoside, characterized in that, It includes the following steps: (1) Dissolve the 2-nitro-glycofuranose donor and the acceptor 1 in dichloromethane under nitrogen protection in an ice bath to obtain reaction system I; dissolve the catalyst 1 in dichloromethane and add it to reaction system I, react at room temperature for 0.5 - 1 h, distill off the solvent under reduced pressure to obtain intermediate product I; (2) Mix the thiol acceptor with intermediate product I, dissolve it in toluene under nitrogen protection, react at room temperature for 0.5 - 1 h, distill off toluene under reduced pressure, and purify by silica gel column chromatography to obtain the final product; In step (1), the receptor 1 is a mercapto serine receptor; the 2-nitro sugar olefin donor is The mercapto serine receptor is The thiol receptor is The peptidoglycan 1,3-dithio glucoside is a compound with the following structure: In the preparation method of the peptidoglycan 1,3-bisthioglucoside, the catalyst 1 is 4-pyrrolidinopyridine; The molar ratio of the 2-nitro-glycofuranose donor to the acceptor 1 is 1:(1 - 1.2); the molar ratio of the 2-nitro-glycofuranose donor to the catalyst 1 is 1:(0.1 - 0.2); the molar ratio of the 2-nitro-glycofuranose donor to the thiol acceptor is 1:(1 - 2).

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