Symmetrical disulfide compound containing sulfoxide group and application thereof in glycosylation reaction

Abstract

The invention belongs to the technical field of organic synthesis, and discloses a symmetric disulfide compound containing a sulfoxide group and application of the symmetric disulfide compound in glycosylation reaction, and the structural general formula of the compound is as shown in formula (I). According to the present invention, the compound represented by the structural general formula (I) contains sulfoxide and disulfide structures, and the sulfinyl forming the sulfoxide and the disulfide bond-containing group are located at the ortho-position of the aromatic ring, such that the compound can be used as the activation reagent for the glycosylation reaction, and particularly, activation of the glycosyl donor and glycosylation reaction can be efficiently promoted by only using 0.25 times of equivalent weight of the glycosyl donor, so that the use of a highly toxic, expensive, unstable or metal-containing activating reagent is avoided, and the problems that the activating reagent of the thioglycoside donor in the existing glycosylation reaction is unstable, is not easy to prepare and often needs equivalent weight or excessive amount are solved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of organic synthesis, and more particularly relates to a symmetrical disulfide compound containing a sulfoxide group and application thereof in glycosylation reactions, which can be used as an activating agent in glycosylation reactions, greatly reducing the amount of activating agent used. BACKGROUND

[0002] Chemical synthesis is an effective means to obtain structurally determined and quality uniform sugar molecules on a large scale, and the key is the effective construction of glycosidic bonds. At present, various sugar donors, activating agents and glycosylation methods have been developed, among which thioglycoside donors are favored due to their stability, availability and versatility, and are one of the most commonly used sugar donors in oligosaccharide synthesis.

[0003] To date, nearly a hundred thioglycoside activating agents have been developed, among which arylsulfenyl sulfonic anhydride (ArSOTf) (J. Am. Chem. Soc. 1998, 120, 435-436) is a highly efficient thioglycoside activating agent. However, the stability of this reagent is poor, and it usually needs to be generated in situ from arylsulfonyl chloride (ArSCl) and silver trifluoromethanesulfonate (AgOTf) and used immediately; in addition, most ArSCl is easily oxidized, rapidly decomposes upon contact with water, and has a strong irritating and foul odor; and AgOTf is a noble metal reagent, which is sensitive to light and has strong hygroscopicity. The above shortcomings limit the widespread application of this reagent. Sugar scientists strive to find activating agents with similar activation ability to ArSOTf and good stability, among which the most notable are the activation combinations of sulfinyl derivatives and trifluoromethanesulfonic anhydride (Tf2O), such as sulfenyl benzenesulfinate MPBT (Org. Lett. 2000, 2, 4067-4069), 1-(benzenesulfinyl)piperidine BSP (J. Am. Chem. Soc. 2001, 123, 9015-9020), diphenyl sulfoxide Ph2SO (Org. Lett. 2003, 5, 1519-1522), and benzene sulfinyl morpholine BSM (Synlett 2006, 17, 2846-2850). In addition to the above activating agents containing sulfoxide groups, compounds containing symmetrical disulfide bonds can also be used as thioglycoside activating agents, such as dimethyl disulfide Me2S2 (Org. Lett. 2007, 9, 4647-4650), which can activate thioglycoside donors and complete glycosylation reactions under low temperature conditions.

[0004] The above reagents all play a decisive role in the efficient coupling between sugar units and / or between sugar units and non-sugar units, but to ensure sufficient activation of thioglycoside donors, it is usually necessary to use an equivalent or even excess amount of activating reagent. In addition, compounds containing a sulfoxide group or a symmetrical disulfide bond have been reported as activating reagents for glycosylation reactions, but there are few reports and applications of compounds containing both structures. Therefore, it is of great research significance and value to develop activating reagents with novel structure, easy preparation, stable properties and lower stoichiometric amount.

[0005] The inventors' team has reported a compound Ⅵ containing a sulfoxide, an asymmetric disulfide bond and a thioether functional group, which can activate thioglycoside donors to form a glycosidic bond under the action of triflic anhydride (Tf2O) at a dosage of 0.5 equivalent, but the activating ability of the reagent is weak and it can only activate high-activity thioglycoside donors. (J. Am. Chem. Soc. 2020, 142, 5498-5503).

[0006] SUMMARY

[0007] In view of the above defects or improvement needs of the prior art, the purpose of the present application is to provide a symmetrical disulfide compound containing a sulfoxide group and its application in glycosylation reactions, wherein by improving the structure of the compound, the compound represented by the general structure (I) contains a sulfoxide and a disulfide structure, and the sulfinyl group constituting the sulfoxide and the group containing the disulfide bond are located at the ortho position of the aromatic ring. The compound is easy to prepare, efficient and stable in chemical properties, and can be used as an activating reagent for glycosylation reactions. In particular, only 0.25 equivalent of the glycosyl donor can efficiently promote the activation of the glycosyl donor and the progress of the glycosylation reaction (that is, one molecule of the activating reagent represented by the general structure (I) can activate four molecules of the glycosyl donor). The use of highly toxic, expensive, unstable or metal-containing activating reagents is avoided, and the problems of unstable, difficult to prepare and often requiring equivalent or excess activating reagents for thioglycoside donors in existing glycosylation reactions are solved.

[0008] To achieve the above-mentioned purpose, according to one aspect of the present application, a symmetrical disulfide compound containing a sulfoxide group is provided, characterized in that the general structure is as shown in formula (I):

[0009]

[0010] wherein O is an oxygen atom; S is a sulfur atom; R is selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl; Ar is a substituted or unsubstituted aromatic ring (consistent with the conventional understanding, the substituents on Ar refer to whether there are substituents at other sites in addition to the connection site of the sulfinyl group and the group containing the disulfide bond).

[0011] As a further preferred embodiment of the present application, said R is selected from the group consisting of substituted or unsubstituted C 1～20 alkyl, substituted or unsubstituted C 6～10 aryl; wherein the substituents are one or more, independently selected from the group consisting of C 1～20 alkyl, C 1～20 alkoxy;

[0012] said Ar is selected from the group consisting of substituted or unsubstituted C 6-14 aryl; wherein the substituents are selected from the group consisting of substituted or unsubstituted C 1～20 alkyl.

[0013] As a further preferred embodiment of the present application, said R is selected from the group consisting of substituted or unsubstituted C 1～6 alkyl, substituted or unsubstituted phenyl; wherein the substituents are one or more, independently selected from the group consisting of C 1～6 alkyl, C 1～20 alkoxy; said halogen is selected from the group consisting of fluorine, chlorine, bromine, iodine;

[0014] said Ar is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; wherein the substituents are C 1～6 alkyl.

[0015] As a further preferred embodiment of the present application, said R is selected from the group consisting of substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted isopropyl; wherein the substituents are one or more, independently selected from the group consisting of methyl, ethyl, octyloxy unsubstituted or substituted with 1-20 halogens; said octyloxy substituted with 1-20 halogens is preferably

[0016]

[0017] said Ar is selected from the group consisting of substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; wherein the substituents are methyl or ethyl; preferably, said Ar is phenyl or naphthyl

[0018] As a further preferred embodiment of the present application, said symmetrical disulfide compound containing a sulfoxide group has a structure as shown in any one of the following structural formula I-1 to structural formula I-6:

[0019]

[0020] According to another aspect of the present application, the present application provides the use of the above-mentioned symmetrical disulfide compound containing a sulfoxide group as an activating agent in a glycosylation reaction;

[0021] Preferably, the molar ratio of the activating agent to the glycosyl donor is (0.25-0.5): 1.

[0022] According to still another aspect of the present application, the present application provides a method for preparing a glycosidation product, characterized in that the method is to activate a glycosyl donor represented by the general structure (II) with the above-mentioned symmetrical disulfide compound containing a sulfoxide group as an activating reagent in the presence of triflic anhydride, and to react with an acceptor represented by the general structure (III) to obtain a glycosidation product represented by the general structure (IV).

[0023] The reaction equation is as follows:

[0024]

[0025] In the glycosyl donor represented by the general structure (II), Gly is a glycosyl group in which one or more hydroxyl groups on a sugar ring are protected by a protecting group; X is a sulfur or selenium atom; R 1 is a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group; preferably, R 1 is independently selected from ethyl (Et), isopropyl (i-Pr), cyclohexyl (Cy), 1-adamantyl (Adm), benzyl (Bn), phenyl (Ph), p-methylphenyl (Tol), 2-ethylphenyl (EP) or 2,6-dimethylphenyl; i o EP) or 2,6-dimethylphenyl;

[0026] The acceptor represented by the general structure (III) is selected from a sugar containing one or more nucleophilic groups, an alcohol, a purine nucleophilic reagent.

[0027] According to still another aspect of the present application, the present application provides a method for preparing a glycosidation product, characterized in that the method is to activate a glycosyl donor represented by the general structure (II) with the above-mentioned symmetrical disulfide compound containing a sulfoxide group as an activating reagent in the presence of triflic anhydride, and to react with an acceptor represented by the general structure (III) to obtain a glycosidation product represented by the general structure (IV).

[0028] The glycosyl donor is specifically represented by the general structure

[0029]

[0030] In the glycosyl donor represented by the general structure (II), Gly is a glycosyl group in which one or more hydroxyl groups on a sugar ring are protected by a protecting group; X is a sulfur or selenium atom; R 1 is a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group;

[0031] The acceptor is specifically represented by the general structure

[0032]

[0033] In the glycosyl donor represented by the general structure (II), Gly is a glycosyl group in which one or more hydroxyl groups on a sugar ring are protected by a protecting group; X is a sulfur or selenium atom; R 2 ​is a substituted or unsubstituted alkyl group, or a substituted or unsubstituted aryl group;

[0034] Preferably, R 1 、R 2 independently selected from ethyl (Et), isopropyl ( i Pr), cyclohexyl (Cy), 1-adamantyl (Adm), benzyl (Bn), phenyl (Ph), p-methylphenyl (Tol), 2-ethylphenyl ( o EP) or 2,6-dimethylphenyl.

[0035] Regarding sequential glycosidation (i.e., the activation reagent participates in the sequential activation of multiple glycosyl donors), for example, the following steps can be referred to:

[0036] (S1) using the aforementioned symmetrical disulfide compound containing a sulfoxide group as an activating reagent, in the presence of trifluoromethanesulfonic anhydride, activating the glycosyl donor represented by the general formula (II) and causing a coupling reaction with the acceptor represented by the general formula (III') to obtain a glycosylated product represented by the general formula (II'); wherein the glycosyl donor represented by the general formula (II) is the first glycosyl unit; and the acceptor represented by the general formula (III') is the second glycosyl unit containing both an activated aglycone on the anomeric carbon and a naked hydroxyl group, and serves as both a glycosyl donor and a glycosyl acceptor;

[0037] (S2) The glycosylated product represented by the general structural formula (II') can serve as a glycosyl donor and is continuously activated in the reaction system without separation, and is coupled with the acceptor represented by the general structural formula (III) or the acceptor represented by the general structural formula (III') to obtain a continuous glycosylated product represented by the general structural formula (V); wherein the acceptor represented by the general structural formula (III) or another acceptor represented by the general structural formula (III') is the third glycosyl unit, or the acceptor represented by the general structural formula (III) may also be a non-sugar unit;

[0038] The reaction equation of the method is as follows:

[0039]

[0040] As a further preferred embodiment of the present invention, the structural formulas of Gly and Gly' are independently selected from the general structural formula (II-a) or the general structural formula (II-b):

[0041]

[0042] Among them, P 1 、P 2 、P 3 、P 4 Each independently selected from: hydrogen, alkyl, alkoxy, acyloxy, substituted amino;

[0043] Preferably, the structural general formula (II-a) has the structure shown in any one of structural formula II-01 to structural formula II-16:

[0044]

[0045] The structural general formula (II-b) has the structure shown in structural formula II-17:

[0046]

[0047] The acceptor shown in formula (III) is a glycosyl acceptor containing one or more free hydroxyl groups, and has the structure shown in any one of structural formula III-01 to structural formula III-11:

[0048]

[0049] Alternatively, the acceptor shown in formula (III) is an alcohol acceptor, and has the structure shown in any one of structural formula III-12 to structural formula III-17:

[0050]

[0051] Alternatively, the acceptor shown in formula (III) is a purine acceptor, and has the structure shown in structural formula III-18:

[0052]

[0053] Alternatively, the acceptor shown in formula (III) is a glycosyl acceptor containing a glycoside ligand capable of being activated at the anomeric carbon, and has the structure shown in any one of structural formula III-19 to structural formula III-20:

[0054]

[0055] The acceptor shown in formula (III’) is a glycosyl acceptor containing a glycoside ligand capable of being activated at the anomeric carbon, and has the structure shown in any one of structural formula III-19 to structural formula III-20:

[0056]

[0057] As a further preferred embodiment of the present application, the molar ratio of the activating agent to triflic anhydride is 1:(1-2), preferably 1:2;

[0058] The molar ratio of the activating agent to the glycosyl donor shown in the structural general formula (II) is 1:(1-6), preferably 1:(1-4);

[0059] The reaction temperature of the glycosylation reaction is -40°C to 30°C;

[0060] The glycosylation reaction is carried out in an organic solvent, which is one of toluene, dichloromethane, acetonitrile, preferably dichloromethane.

[0061] Compared with the prior art, the compound of the structural general formula (I) obtained by the technical scheme of the present application contains a sulfoxide and a disulfide structure, and the sulfinyl group constituting the sulfoxide and the group containing the disulfide bond are located at the ortho position of the aromatic ring, having a special relative positional relationship; the compound can be especially applied to a glycosylation reaction as an activating agent, greatly reducing the amount of the activating agent. The compound containing a sulfoxide group and a symmetrical disulfide structure as shown in the structural general formula (I) is used as an activating agent, under the action of trifluoromethanesulfonic anhydride, to activate a thioside or selenoside donor (II) while releasing a plurality of thiophilic intermediates, which can continue to participate in the activation of the thioside or selenoside donor. In other words, one molecule of the activating agent (I) can activate four molecules of the glycosyl donor. Therefore, based on the compound of the structural general formula (I) obtained by the present application, only 0.25 equivalent of the glycosyl donor (that is, the molar ratio of the amount of the activating agent to the glycosyl donor is 0.25:1) is needed to effectively promote the activation of the glycosyl donor and the glycosylation reaction, and the problems of instability, difficulty in preparation, and the need for an equivalent or excess amount of the activating agent for the activation of the thioside donor in the prior art glycosylation reaction can be solved.

[0062] As shown in the examples below, for the construction of a glycosidic bond by activating a high-activity donor, the compound of the structural general formula (I) of the present application needs only 0.25 equivalent as an activating agent (while the activating agent in the prior art, such as the compound of the structural formula VI introduced in the “BACKGROUND” section above, needs 0.5 equivalent); and for the construction of a glycosidic bond by activating a low-activity donor (such as a disarmed glycosyl donor), the effect of the compound of the structural general formula (I) of the present application is particularly outstanding, and an excellent yield can be achieved when the amount is 0.5 equivalent (while the compound of the structural formula VI needs 0.5 equivalent, and the reaction effect is poor and the yield is not ideal, as shown in Comparative Example 2 below).

[0063] The preparation method of the compound of the structural general formula (I) of the present application is simple, for example, the following synthesis route can be used:

[0064]

[0065] That is, a chlorinated hydrocarbon is used as a reaction raw material, a thioacetyl group is introduced at the benzyl position, the acetyl group is hydrolyzed and removed to obtain a benzyl mercaptan derivative, a symmetrical disulfide is prepared by metal-catalyzed oxidative coupling, and then the symmetrical disulfide compound containing a sulfoxide group is obtained by selective oxidation of the disulfide.

[0066] The compound of the structural general formula (I) obtained by the present application can be used as an activating agent in glycosylation reaction, which can include the following two cases:

[0067] i) The compound of the structural general formula (I) is used as an activating agent to promote the reaction between a glycosyl donor and an acceptor in the presence of triflic anhydride (Tf2O), thereby obtaining a glycosylation product; for example,

[0068]

[0069] Or,

[0070] ii) The compound of the structural general formula (I) is used as an activating agent to pre-activate a glycosyl donor in the presence of triflic anhydride (Tf2O), and then the activated glycosyl donor is coupled with a glycosyl acceptor (for example, the glycosyl acceptor can be represented by the structural general formula (III')) to obtain a glycosylation product, which can be further activated as a glycosyl donor and coupled with another acceptor (for example, the acceptor can be represented by the structural general formula (III')) to obtain a continuous glycosylation product, thereby realizing the one-pot connection of multiple glycosyl units or the one-pot connection of multiple glycosyl units and non-sugar units; for example,

[0071]

[0072] In general, the present application can achieve the following beneficial effects:

[0073] 1) The compound of the structural general formula (I) of the present application has a novel structure, contains a sulfoxide group and a symmetric disulfide bond structure that meet specific relative positional relationships, is chemically stable (can be stored at room temperature in an air atmosphere) and has no irritating odor, and is easy and efficient to prepare, and the raw materials are cheap and easy to obtain.

[0074] 2) The compound of the structural general formula (I) of the present application can be used as an activating agent in glycosylation reaction, and when it is used in combination with triflic anhydride (Tf2O), the dosage of the activating agent can be reduced to 0.25 equivalent of the thioglycoside donor (that is, only 0.25 equivalent of the activating agent is needed for the construction of one glycosidic bond, 0.5 equivalent of the activating agent is needed for the construction of two glycosidic bonds, and so on), thereby effectively solving the problem that an equivalent amount of activating agent is needed for the activation of thioglycoside in glycosylation reaction.

[0075] 3) The activating agent of the structural general formula (I) of the present application can activate various thioglycoside / seleoglycoside donors, and is widely used in various glycosylation reactions, thereby avoiding the use of commonly used toxic, expensive, unstable or metal-containing activating agents in the activation process of glycosyl donors, and realizing the safe and efficient performance of glycosylation reaction.

[0076] 4) The present application also provides a method for realizing continuous one-pot glycosylation based on the activated reagent represented by the structural general formula (I). Specifically, the thio- or selenoglycoside donor (II) is activated and coupled with the acceptor in situ to generate multiple thiophilic intermediates with the aid of the reagent represented by the structural general formula (I), and the generated thiophilic intermediates can continue to participate in the activation of the thio- or selenoglycoside donor, so that the combination of the activated reagent can be added at one time, the sequential activation of different glycosyl donors can be accurately controlled, and the sequential construction of multiple glycosidic bonds and the one-pot connection between multiple glycosyl units (or between the glycosyl unit and a non-sugar unit) can be realized. BRIEF DESCRIPTION OF DRAWINGS

[0077] Figure 1 is a comparison chart of the nuclear magnetic hydrogen spectrum of compound I-1 before and after being placed at room temperature (30-35 degrees Celsius) for one month without light protection and in an air atmosphere in Example 7.

[0078] Figure 2 is a comparison chart of the nuclear magnetic hydrogen spectrum of compound I-2 before and after being placed at room temperature (30-35 degrees Celsius) for one month without light protection and in an air atmosphere in Example 7. DETAILED DESCRIPTION

[0079] In order to make the objectives, technical solutions and advantages of the present application clearer, the present application will be further described in detail below with reference to examples. It should be understood that the specific examples described herein are only used to explain the present application and do not limit the present application. In addition, the technical features involved in each embodiment of the present application described below can be combined with each other as long as they do not conflict with each other.

[0080] In the present application, the "substituted or unsubstituted" group means that the group can be substituted by the substituent defined later, or the group can be unsubstituted; if it is substituted, the substituent can be located at any position that can be substituted.

[0081] Unless otherwise specified, the raw materials or reagents used in the present application are commercially available. All reagents are of commercial grade and are used according to the standard received. All moisture-sensitive reactions are carried out in an argon atmosphere. The reactions are monitored by thin layer chromatography (TLC), detected by ultraviolet absorption (254 nm), and if necessary, sprayed with 10% sulfuric acid ethanol solution and carbonized at 80-150°C for color development. Flash column chromatography uses silica gel H. 1 H and 13 C nuclear magnetic resonance spectrum, deuterated chloroform (CDCl3) is used as deuterated reagent, recorded on Bruker AV 400, Bruker Av 600. The chemical shift (δ) is expressed in ppm, with tetramethylsilane as the internal standard. The coupling constant (J) is expressed in Hz.

[0082] Unless otherwise indicated, the scientific and technical terms and abbreviations used in the present application have the meanings commonly understood by one of ordinary skill in the art. For example, "equivalents" in the present application means the ratio of the amount of substance of each substance involved in the reaction; again, for example, the meanings of some abbreviations are shown in Table 1:

[0083] Table 1

[0084] Abbreviations Chinese meaning Abbreviations Chinese meaning Me methyl Ph phenyl Et ethyl Tol p-tolyl i Pr]]> ​ isopropyl Adm 1-adamantyl Phth phthaloyl TBS tert-butyldimethylsilyl Ac acetyl Fmoc fluorenylmethoxycarbonyl Bn benzyl Cbz benzyloxycarbonyl Bz benzoyl Toluene toluene Tf trifluoromethanesulfonyl DCM dichloromethane MeCN acetonitrile DTBMP 2,6-di-tert-butyl-4-methylpyridine

[0085] The symmetrical disulfide reagent containing a sulfoxide group as shown in the general structure (I) in the present application, as shown in Table 2, for example, can be:

[0086] Table 2 Activated reagent shown in the general structure (I) in the present application

[0087]

[0088]

[0089] The activated reagent as shown in the general structure (I) in the present application can be prepared according to the following method:

[0090]

[0091] The method includes two stages of symmetrical disulfide bond construction and selective oxidation, and the general procedure A is as follows:

[0092] 1) Dissolve the corresponding chlorohydrocarbon (1.0 equivalent) in acetone (concentration c = 0.5 M), add potassium carbonate (1.1 equivalent), slowly add thioacetic acid (1.1 equivalent) under stirring at 0°C, then warm to room temperature and react until the chlorohydrocarbon is completely consumed. Dilute the reaction system with ethyl acetate, wash with water, saturated sodium bicarbonate, and saturated sodium chloride solution in sequence. Then dry the organic phase with anhydrous sodium sulfate, filter and concentrate, and purify the crude product by silica gel column chromatography to obtain the thioacetylated derivative.

[0093] 2) Dissolve the thioacetylated derivative (1.0 equivalent) in methanol (concentration c = 0.4 M), add potassium carbonate (0.2 equivalent), and react at 60°C until the raw material is completely consumed. Concentrate the reaction solution after suction filtration with diatomite to obtain the crude thiol derivative after removal of the acetyl group, which is directly used in the next step.

[0094] 3) Dissolve the above mixture in acetonitrile (concentration c = 0.4 M), add sodium iodide (0.2 equivalent) and ferric chloride (0.1 equivalent) in sequence, stir at room temperature under air atmosphere for 1 hour. Concentrate to remove acetonitrile. Dilute the reaction system with ethyl acetate, wash with water, saturated sodium bicarbonate, and saturated sodium chloride solution in sequence. Then dry the organic phase with anhydrous sodium sulfate, filter and concentrate, and purify the crude product by silica gel column chromatography to obtain the non-oxidized precursor of the symmetrical disulfide reagent containing a sulfoxide group.

[0095] 4) The non-oxidized reagent precursor (1.0 eq) was dissolved in dichloromethane (concentration c = 0.1 M), cooled to 0 °C, and a solution of the oxidizing agent meta-chloroperoxybenzoic acid (2.0 eq) in dichloromethane (concentration c = 0.3 M) was added slowly, keeping the temperature at 0 °C for 0.5 h. The reaction was terminated by adding saturated sodium thiosulfate solution to the reaction flask. The reaction mixture was diluted with ethyl acetate and washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution successively. The organic phase was then dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to give the symmetrical disulfide reagent (I) containing a sulfoxide group.

[0096] The following are specific examples (the yield "…% for 4 steps" appearing hereinafter, unless otherwise specified, refers to the total yield of the four steps of the above general procedure A):

[0097] Example 1: Synthesis of compound I-1

[0098]

[0099] Referring to the general procedure A, 2-(2-propylthio)benzyl chloride was used as the starting material to give I-1 as a light yellow oily liquid (5.82 g, yield 74% for 4 steps). 1 H NMR (400 MHz, CDC13) δ 7.88-7.82 (2H, m, Ar-H), 7.51-7.41 (4H, m), 7.35-7.28 (2H, m), 3.90 (1H, d, J = 12.8 Hz, Bn-H), 3.84 (1H, d, J = 12.8 Hz, Bn-H), 3.76 (2H, d, J = 12.8 Hz, Bn-H), 3.00-2.85 (2H, m, -CH(CH3)2), 1.25 (3H, d, J = 6.8 Hz, -CH(CH3)2), 1.23 (3H, d, J = 7.2 Hz), 1.16 (3H, d, J = 6.18 Hz, -CH(CH3)2), 1.16 (3H, d, J = 6.8 Hz, CH(CH3)2). 13 C NMR (100 MHz, CDC13) δ 141.7, 141.6, 135.2, 131.3, 131.3, 131.2, 131.2, 128.9, 128.9, 125.9, 125.9, 54.5, 54.5, 39.3, 39.2, 17.4, 17.3, 13.8, 13.7. HRMS (ESI-TOF) m / z: [M + Na] + calc. for C 20 H 26O2S4Na 449.0708; Found 449.0732.

[0100] Example 2: Synthesis of compound I-2

[0101]

[0102] Referring to general procedure A with 2-methylthiobenzyl chloride as starting material, I-2 was obtained as a white solid (0.5 g, yield 65% for 4 steps). 1 H NMR (600 MHz, CDC13) δ 8.02 (2H, dd, J = 7.8, 2.4 Hz, Ar-H), 7.54 (2H, t, J = 7.8 Hz, Ar-H), 7.48-7.44 (2H, m, Ar-H), 7.25-7.24 (2H, m, Ar-H), 3.94 (2H, d, J = 12.8 Hz, -CH2Ph), 3.82 (1H, d, J = 12.8 Hz, -CH2Ph), 3.72 (1H, d, J = 12.8 Hz, -CH2Ph), 2.77 (1H, s, -CH3), 2.75 (1H, s, -CH3). 13 C NMR (150 MHz, CDC13) δ 145.2, 134.2, 134.2, 131.5, 131.2, 131.1, 129.9, 129.8, 124.5, 124.5, 44.1, 44.0, 39.2, 39.2. HRMS (ESI-TOF) m / z: [M + Na] + calc. for C 16 H 18 O2S4Na 393.0082; Found 393.0075.

[0103] Example 3: Synthesis of compound I-3

[0104]

[0105] Referring to general procedure A with 2-((4-methylphenyl)thio)benzyl chloride as starting material, I-3 was obtained as a white solid (0.4 g, yield 60% for 4 steps). 1H NMR (600 MHz, CDC13) δ 7.82 (2H, t, J = 7.2 Hz, Ar-H), 7.49-7.46 (4H, m, Ar-H), 7.44-7.38 (4H, m, Ar-H), 7.28 (1H, d, J = 7.2 Hz, Ar-H), 7.25 (1H, d, J = 7.8 Hz, Ar-H), 7.23-7.21 (4H, m, Ar-H), 3.94-3.87 (3H, m, -CH2Ph), 3.83 (1H, d, J = 12.6 Hz, -CH2Ph), 2.34 (6H, s, -CH3). 13 C NMR (150 MHz, CDC13) δ 144.4, 144.3, 141.9, 141.9, 141.5, 135.7, 135.6, 131.5, 131.3, 131.3, 130.3, 129.4, 129.4, 126.3, 126.2, 125.9, 39.6, 39.6, 21.6. HRMS (ESI-TOF) m / z: [M + Na] + calc. for C 28 H 26 O2S4Na 545.0708; Found 504.0704.

[0106] Example 4: Synthesis of compound I-4

[0107]

[0108] The known compound S1 was synthesized according to the literature (Chin. Chem. Lett., 2017, 28, 1693-1700, Chem. Sci., 2022, 13, 8759-8765). S1 (1.0 eq) was weighed into a reaction flask, dissolved in dichloromethane (concentration c = 0.2 M), and a solution of thionyl chloride (SOCl2) in dichloromethane (1.5 eq) was slowly added dropwise under ice bath. After the addition was completed, it was moved to room temperature and reacted for 0.5 h. After the reaction was completed, the reaction system was diluted with ethyl acetate, and washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution in turn. Then the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography to obtain colorless liquid S2 (yield 64%). 1H NMR (400 MHz, CDC13) δ 7.53-7.51 (1H, m, Ar-H), 7.46-7.45 (1H, m, Ar-H), 7.29-7.27 (2H, m, Ar-H), 4.84 (2H, s, -CH2Ph), 3.71 (4H, t, J = 6.6 Hz), 3.69-3.64 (4H, m), 3.38-3.35 (1H, m, SCH), 2.40-2.32 (4H, m, -CH2 H 2C H 2C6F 13 ). 13 CNMR (150 MHz, CDC13) δ 139.9, 134.5, 134.1, 130.8, 129.4, 128.6, 70.4, 63.3 (t, J = 4.0 Hz, -CH2 C H2CH2C6F 13 ), 49.1, 44.8, 31.5 (t, J = 21.6 Hz, -CH2 C H2C6F 13 ). HRMS (ESI-TOF) m / z: [M + Na] + calc. for C 26 H 19 ClF 26 O2SNa 947.0271; Found 947.0276.

[0109] Reference to General Procedure A with compound S2 as starting material to give colorless oil liquid I-4 (30 mg, yield 50% for 4 steps). 1 H NMR (400 MHz, CDC13) δ 7.89 (2H, d, J = 7.2 Hz, Ar-H), 7.51-7.44 (4H, m, Ar-H), 7.32-7.28 (2H, m, Ar-H), 3.94 (1H, d, J = 13.2 Hz, -CH2Ph), 3.84 (1H, d, J = 13.2 Hz, -CH2Ph), 3,76 (4H, d, J = 5.2 Hz, -CH(C H 2)2)), 3.71 (1H, d, J = 13.2 Hz, -CH2Ph), 3.70-3.58 (13H, m), 3.25-3.18 (2H, m, -C H (CH2)2)), 2.36-2.18 (8H, m). 13C NMR (150 MHz, CDC13) δ 141.2, 141.2, 135.4, 133.7, 131.6, 131.6, 131.5, 131.4, 130.4, 130.0, 129.1, 129.0, 128.4, 125.6, 125.6, 66.8, 64.4, 64.3, 64.3, 63.5, 63.3, 38.6, 38.5, 31.4, 31.4, 29.9. HRMS (ESI-TOF) m / z: [M + Na] + calc. for C 52 H 38 F 52 C6S4Na 1897.0613; Found 1897.0637.

[0110] Example 5: Synthesis of compound I-5

[0111]

[0112] The known compound S3 was synthesized according to the literature (Tetrahedron Lett. 1980, 21, 4203-4206, J. Am. Chem. Soc. 2020, 142, 5498-5503). S3 (1.0 eq) and 4-dimethylaminopyridine (DMAP) were weighed into a reaction flask and dissolved in dichloromethane (c = 0.2 M), and triethylamine (2.0 eq) and p-toluenesulfonyl chloride (2.0 eq) were added successively under ice bath. After the addition was completed, it was removed to room temperature and reacted for 24 h. After the reaction was completed, the reaction system was diluted with ethyl acetate and washed successively with water, saturated sodium bicarbonate, and saturated sodium chloride solution. Then the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography to obtain oily liquid S4 (yield 78%). 1 H NMR (400 MHz, CDC13) δ 7.34 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.21 (1H, t, J = 7.6 Hz, Ar-H), 7.12 (1H, d, J = 7.6 Hz, Ar-H), 4.96 (2H, s, -CH2Ph), 3.41 (1H, hept, J = 6.8 Hz, -C H (CH3)2), 2.79 (2H, q, J = 7.6 Hz, -C H 2CH3), 1.29 (6H, d, J = 7.2 Hz, -CH(C H 3)2), 1.27 (3H, t, J = 7.2 Hz, -CH2C H 3). 13C NMR (150 MHz, CDC13) δ 144.4, 139.2, 133.7, 129.5, 127.8, 127.1, 41.7, 40.3, 29.9, 25.9, 22.6, 15.6. HRMS (ESI-TOF) m / z: [M + O + Na] + calc. for C 12 H 17 ClSONa 267.0581; Found 267.0582.

[0113] Referring to general procedure A, I-5 was obtained as an oily liquid (0.1 g, yield 51% for 4 steps) using S4 as starting material. 1 H NMR (400 MHz, CDC13) δ 7.73 (2H, d, J = 8.0 Hz, Ar-H), 7.44 (2H, td, J = 7.6, 2.4 Hz, Ar-H), 7.35-7.32 (2H, m, Ar-H), 4.16-4.08 (3H, m, -CH2Ph), 3.95 (1H, d, J = 12.4 Hz, -CH2Ph), 3.00-2.93 (2H, m, -CH2Ph), 2.82-2.72 (4H, m, -CH2Ph), 2.68-2.62 (2H, m, -CH2Ph), 2.58-2.52 (2H, m, -CH2Ph), 2.48-2.42 (2H, m, -CH2Ph), 2.36-2.30 (2H, m, -CH2Ph), 2.28-2.22 (2H, m, -CH2Ph), 2.20-2.14 (2H, m, -CH2Ph), 1.97-1.91 (2H, m, -CH2Ph), 1.86-1.80 (2H, m, -CH2Ph), 1.74-1.68 (2H, m, -CH2Ph), 1.64-1.58 (2H, m, -CH2Ph), 1.54-1.48 (2H, m, -CH2Ph), 1.44-1.38 (2H, m, -CH2Ph), 1.36-1.30 (2H, m, -CH2Ph), 1.26-1.20 (2H, m, -CH2Ph), 1.18-1.12 (2H, m, -CH2Ph), 1.10 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 1.08 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 0.94 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 0.90 (3H, t, J = 7.6 Hz, -CH2C(CH3)2). H (CH3)2)), 2.82-2.72 (4H, m, -CH2Ph), 2.68-2.62 (2H, m, -CH2Ph), 2.58-2.52 (2H, m, -CH2Ph), 2.48-2.42 (2H, m, -CH2Ph), 2.36-2.30 (2H, m, -CH2Ph), 2.20-2.14 (2H, m, -CH2Ph), 1.97-1.91 (2H, m, -CH2Ph), 1.86-1.80 (2H, m, -CH2Ph), 1.74-1.68 (2H, m, -CH2Ph), 1.64-1.58 (2H, m, -CH2Ph), 1.54-1.48 (2H, m, -CH2Ph), 1.44-1.38 (2H, m, -CH2Ph), 1.36-1.30 (2H, m, -CH2Ph), 1.26-1.20 (2H, m, -CH2Ph), 1.18-1.12 (2H, m, -CH2Ph), 1.10 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 1.08 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 0.94 (3H, t, J = 7.6 Hz, -CH2C(CH3)2), 0.90 (3H, t, J = 7.6 Hz, -CH2C(CH3)2). H 2CH3), 1.29-2.23 (12H, m, -CH2C(CH3)2), 1.18 (6H, d, J = 6.8 Hz, -CH(C(CH3)2)2), 1.16 (6H, d, J = 6.8 Hz, -CH(C(CH3)2)2). H 3,-CH(C H 3)2)), 1.17 (6H, d, J = 6.8 Hz, -CH(C H 3)2)). 13 C NMR (150 MHz, CDC13) δ 144.4, 139.2, 133.7, 129.5, 127.8, 127.1, 41.7, 40.3, 29.9, 25.9, 22.6, 15.6. HRMS (ESI-TOF) m / z: [M + O + Na] + calc. for C 24 H 34 O2S4Na 505.1334; Found 505.1328.

[0114] Example 6: Synthesis of compound I-6

[0115]

[0116] As shown in the synthetic route, first according to the method of synthesizing compound XXXV in the literature (Monatsh. Chem. 1965, 96, 182-207), S5 was used as raw material, and compound S6 (170 mg, 3% for 4 steps) was synthesized by 4-step reaction. 1 HNMR (400 MHz, CDC13) δ 7.99 (1H, s, Ar-H), 7.87 (1H, s, Ar-H), 7.84-7.82 (1H, m, Ar-H), 7.71-7.69 (1H, m, Ar-H), 7.51-7.45 (2H, m, Ar-H), 7.30-7.19 (5H, m, Ar-H), 4.88 (2H, s, -CH2). 13 CNMR (150 MHz, CDC13) δ 136.3, 136.1, 134.1, 133.8, 133.0, 131.7, 130.0, 130.0, 129.5, 128.0, 127.5, 127.3, 127.2, 127.0, 45.2. HRMS (ESI-TOF) m / z: [M+Na] + calcd for C 17 H 13 ClOSNa 323.0268; Found 323.0274.

[0117] Referring to the general procedure A, orange liquid I-6 (15 mg, yield 50% for 4 steps) was obtained using S6 as the starting material. 1 H NMR (400 MHz, CDC13) δ 8.44 (2H, d, J = 9.6 Hz, Ar-H), 7.91 (2H, d, J = 7.6 Hz, Ar-H), 7.80 (2H, t, J = 7.6 Hz, Ar-H), 7.62-7.51 (10H, m, Ar-H), 7.40-7.33 (6H, m, Ar-H), 3.84-3.72 (4H, m, -CH2Ph). 13 C NMR (150 MHz, CDC13) δ 144.7, 144.6, 141.3, 141.2, 134.3, 132.7, 132.7, 131.6, 131.6, 131.2, 131.1, 131.0, 130.9, 129.7, 128.9, 128.8, 128.6, 128.0, 128.0, 127.6, 127.4, 127.2, 126.5, 126.4, 40.1, 40.0. HRMS (ESI-TOF) m / z: [M+Na] + calcd for C 34 H 26O2S4Na 617.0708; Found 617.0709.

[0118] Example 7: Stability test of compound I (for example, compound I-1, I-2 was placed at room temperature without light protection for one month)

[0119] After compound I-1 was placed at room temperature (30-35 degrees Celsius) without light protection and in air atmosphere for one month, the nuclear magnetic hydrogen spectrum did not change (as shown in Figure 1 It can be seen that compound I-1 is not sensitive to light and heat (and compound I-1 can be stored for several years at low temperature conditions (-20 degrees Celsius)).

[0120] Similarly, after compound I-2 was placed at room temperature (30-35 degrees Celsius) without light protection and in air atmosphere for one month, the nuclear magnetic hydrogen spectrum did not change (as shown in Figure 2 It can be seen that compound I-2 is not sensitive to light and heat.

[0121] The symmetrical disulfide compound (I) containing a sulfoxide group of the present application can be used as an activating agent in a glycosylation reaction. Based on this use, the present application provides a method for activating a donor to construct a glycosidic bond in cooperation with triflic anhydride, using an activating agent of structural general formula (I).

[0122] The method comprises the steps of:

[0123] The glycosyl donor (II), the acceptor (III) and the activating agent (I) are mixed, and then triflic anhydride is added to undergo a glycosylation reaction to obtain a glycosylation product (IV); the reaction formula is as follows:

[0124]

[0125] Alternatively, the method comprises the steps of:

[0126] The glycosyl donor (II) and the activating agent (I) are mixed, and then triflic anhydride and the acceptor (III') are sequentially added to undergo a first glycosylation reaction to obtain a first glycosylation product (II'); then the acceptor (III) or (III') is added again to continue the glycosylation reaction to obtain a continuous glycosylation product (V); the reaction formula is as follows:

[0127]

[0128] Detailed experimental processes are shown in the following examples.

[0129] Examples 8-10: Effect of the amount of the activating agent of the present application on the glycosylation reaction

[0130] The glycosylation reaction of glycosyl donor II-01 and glycosyl acceptor III-01 under the action of activating reagent I-1 was taken as an example, and the effects of different amounts of activating reagent combined with triflic anhydride (Tf2O) on the glycosylation reaction were investigated. The results showed that different amounts of activating reagent combined with triflic anhydride (Tf2O) could realize the coupling of glycosyl donor and acceptor (such as

[0131] Table 3).

[0132]

[0133] Table 3 Effects of different amounts of activating reagent on glycosylation reaction

[0134]

[0135]

[0136] Operation steps: take donor II-01 (0.06 mmol, 1.2 equivalents), activating reagent formula I-1 (amount of equivalents as shown in Table 3) and glycosyl acceptor III-01 (0.05 mmol, 1.0 equivalent) in a reaction bottle, toluene azeotrope with water twice, then add activated molecular sieves and 2,6-di-tert-butyl-4-methylpyridine (DTBMP) (0.06 mmol, 1.2 equivalents). Add anhydrous dichloromethane (0.1 M) under argon atmosphere, cool the reaction bottle to 0°C and stir for 10 minutes, and use a microsyringe to add triflic anhydride (amount of equivalents as shown in Table 3). React at 0°C for 1 hour, then warm to 30°C, continue to react for 5 hours until the raw material is completely consumed. Add triethylamine (0.1 ml) to the above reaction bottle to terminate the reaction, filter through diatomite, and concentrate. The crude product is purified by silica gel column chromatography to obtain compound IV-01 as colorless syrup. R f = 0.48 (PE:EA = 3:1). 1H NMR (400MHz, CDCl3) δ7.34-7.19(28H,m,Ar-H),7.15-7.11(2H,m),4.95(1H,t,J=8.4Hz,H-2'),4.78-4.72(3H,m),4.70 (1H,d,J=12.0Hz,Bn-H),4.65-4.58(4H,m),4.54(1H,d,J=12.4Hz,Bn-H),4.51(1H,d,J=11.2Hz,Bn-H),4.46(1H,d,J=1 2.4Hz,Bn-H),4.43(2H,d,J=12.0Hz,Bn-H), 4.36(1H,d,J=12.0Hz,Bn-H), 4.00(1H,d,J=1.6Hz), 3.84(1H,t,J=6.0Hz), 3.80(1H,dd,J=10.0,2.8Hz),3.78-3.72(2H,m),3.68-3.56,(5H,m),3.36-3.29(4H,m,-OMe,H-5),1.70(3H,s,-COCH3).

[0137] Comparative Example 1: Effect of the Amount of Activating Reagent Represented by Structural Formula (VI) on the Glycosidation Reaction

[0138]

[0139]

[0140] Procedure: donor II-01 (0.06 mmol, 1.2 equivalents), activation reagent formula VI (equivalents as shown in Table 3) and glycosyl acceptor III-01 (0.05 mmol, 1.0 equivalents) were placed in a reaction flask, and water was azeotroped with toluene twice, followed by the addition of activated Molecular sieves and 2,6-di-tert-butyl 4-methylpyridine (DTBMP) (0.06mmol, 1.2 equivalents). Anhydrous dichloromethane (0.1M) was added under an argon atmosphere, the reaction flask was cooled to 0°C and stirred for 10 minutes, and trifluoromethanesulfonic anhydride was added using a microinjector (the amount equivalent is shown in Table 3). The reaction was carried out at 0°C for 1 hour, then the temperature was raised to 30°C and the reaction was continued for 5 hours until the raw materials were completely consumed. Triethylamine (0.1ml) was added to the above reaction flask to terminate the reaction, and the mixture was concentrated after filtration through diatomaceous earth. The crude product was purified by silica gel column chromatography to obtain a colorless syrupy compound IV-01. R f =0.48(PE:EA=3:1).

[0141] Examples 11-18: Application of different activation reagents of the present invention in glycosidation reactions

[0142] The glycosylation reaction of the glycosyl donor II-01 and the glycosyl acceptor III-02 under the action of different activating reagents (I) was taken as an example, and the application of the different activating reagents in the glycosylation reaction was investigated. The results show that the glycosyl donor II-01 and the glycosyl acceptor III-02 can be coupled smoothly under the action of different activating reagents (I) in different reaction solvents.

[0143]

[0144] Table 4 Application of different activating reagents in glycosylation reaction

[0145]

[0146] Operation steps: take the donor II-01 (0.06 mmol, 1.2 equivalents), different activating reagents formula I (0.3 equivalents) and glycosyl acceptor III-02 (0.05 mmol, 1.0 equivalent) in a reaction bottle, toluene azeotrope water twice, then add activated molecular sieves and 2,6-di-tert-butyl-4-methylpyridine (DTBMP) (0.06 mmol, 1.2 equivalents). Under argon atmosphere, add solvent (0.1 M), cool the reaction bottle to 0℃ and stir for 10 minutes, use microsyringe to add triflic anhydride (0.6 equivalents). React at 0℃ for 1 hour, then warm to 30℃, continue to react for 5 hours until the raw material is completely consumed. Add triethylamine (0.1 ml) to the above reaction bottle to terminate the reaction, filter through diatomite, concentrate, and purify the crude product by silica gel column chromatography to obtain compound IV-02 in colorless syrup. 1H NMR (400 MHz, CDC13) δ 7.39-7.19 (15H, m, Ar-H), 4.99 (1H, t, J = 9.2 Hz), 4.95 (1H, d, J = 12.0 Hz, -CH2Ph), 4.92 (1H, t, J = 9.2 Hz), 4.86 (1H, t, J = 8.8 Hz, H-2'), 4.72-4.69 (3H, m, -CH2Ph), 4.56 (1H, d, J = 11.6 Hz, -CH2Ph), 4.57-4.54 (2H, m, -CH2Ph), 4.46 (1H, d, J = 7.6 Hz, H-1'), 4.39 (1H, d, J = 12.0 Hz, -CH2Ph), 4.11 (1H, dd, J = 12.4, 4.0 Hz), 3.87-3.78 (3H, m), 3.73 (1H, dd, J = 10.8, 2.8 Hz), 3.59-3.55 (2H, m), 3.44 (1H, dd, J = 8.8, 3.6 Hz, H-2), 3.34 (1H, s, -OCH3), 3.27 (1H, m, H-5), 1.97 (3H, s, -COCH3), 1.95 (3H, s, -COCH3), 1.92 (3H, s, -COCH3), 1.92 (3H, s, -COCH3).

[0147] Examples 19-25: Activation of different glycosyl donors by the activating reagent of the present application

[0148] The activation of different glycosyl donors by the activating reagent of the present application was investigated by taking the glycosylation reaction of different glycosyl donors II and glycosyl acceptor III-01 under the action of the activating reagent I-1 of the present application as an example. The results showed that the glycosyl donors II containing different end group protecting groups and the glycosyl acceptor III-01 all showed good glycosylation effect under the action of the activating reagent I-1, indicating that the activating reagent (I) of the present application has a good effect of activating glycosyl donors.

[0149]

[0150] Table 5 Activation of different glycosyl donors by the activating reagent of the present application

[0151]

[0152] Operation steps: weigh the donor II (0.06 mmol, 1.2 equivalents), the symmetrical disulfide reagent I-1 containing a sulfoxide group (0.06 mmol, 0.6 equivalents) and the glycosyl acceptor III-01 (0.05 mmol, 1.0 equivalent) into a reaction bottle, and then add the activated Molecular sieves. Anhydrous dichloromethane (0.1 M) was added under argon atmosphere, cooled to 0 °C, followed by the addition of triflic anhydride (0.06 mmol, 1.2 eq). The reaction was allowed to proceed for 1 h. Triethylamine (0.1 ml) was added to the reaction flask to quench the reaction, which was filtered through celite and concentrated. The crude product was purified by silica gel column chromatography to give compound IV-03 as colorless syrup. Rf = 0.39 (PE:EA = 2:1). f = 0.39 (PE:EA = 2:1). 1 H NMR (400 MHz, CDC13) δ 7.39 - 7.21 (15H, m), 5.18 (1H, t, J = 9.6 Hz), 5.03 (1H, t, J = 10.0 Hz), 4.98 (1H, dd, J = 10.0, 8.0 Hz, H-2'), 4.83 (1H, d, J = 11.6 Hz), 4.77 (1H, d, J = 8.0 Hz, H-1'), 4.73 (1H, d, J = 12.0 Hz, -CH2Ph), 4.65 (1H, d, J = 12.0 Hz, -CH2Ph), 4.61 (1H, d, J = 3.6 Hz, H-1), 4.56 (1H, d, J = 12.4 Hz, -CH2Ph), 4.53 (1H, d, J = 12.8 Hz, -CH2Ph), 4.48 (1H, d, J = 12.0 Hz, -CH2Ph), 4.14 (1H, dd, J = 12.4, 4.4 Hz), 4.04 - 3.97 (2H, m), 3.89 - 3.83 (2H, m,), 3.75 (1H, dd, J = 10.0, 3.6 Hz), 3.65 (1H, dd, J = 10.0, 5.6 Hz, H-3), 3.57 - 3.49 (2H, m), 3.34 (3H, s), 2.00 (3H, s,), 1.99 (3H, s), 1.98 (3H, s), 1.79 (3H, s).

[0153] Comparative Example 2: Activation of a de-activated glycosyl donor with an activated reagent of general structure (VI)

[0154]

[0155] Procedure: The donor II-08 (0.06 mmol, 1.2 eq), activated reagent of VI (0.06 mmol, 0.6 eq) and the glycosyl acceptor III-01 (0.05 mmol, 1.0 eq) were weighed into a reaction flask, co-evaporated with toluene twice to remove water, followed by the addition of activated reagent of VI (0.06 mmol, 0.6 eq) and the reaction was allowed to proceed for 1 h. Molecular sieves. Anhydrous dichloromethane (0.1 M) was added under an argon atmosphere and cooled to 0°C. Trifluoromethanesulfonic anhydride (0.06 mmol, 1.2 equivalents) was then added. The reaction was allowed to proceed for 1 hour, with a small amount of donor conversion. The temperature was then raised to 30°C and the reaction time extended to 15 hours. However, the donor activation was not complete. Triethylamine (0.1 ml) was added to the reaction flask to terminate the reaction. The mixture was filtered through diatomaceous earth and concentrated. The crude product was purified by silica gel column chromatography to obtain compound IV-03 as a colorless syrup in a yield of 17%.

[0156] Examples 26-43

[0157] Unless otherwise specified, the standard operating procedure for the glycosidation reaction of Examples 26-43 is as follows: the glycosyl donor, activation reagent (I) and glycosyl acceptor are placed in a reaction flask, azeotroped with toluene twice, and then the activated Molecular sieves (100 mg / ml in CH2Cl2 solution) were sealed with a rubber stopper. Anhydrous dichloromethane (0.1 M) was added under an argon atmosphere. The reaction flask was cooled to 0°C, followed by the addition of trifluoromethanesulfonic anhydride (Tf2O). After completion of the reaction, triethylamine (0.1 ml) was added to the reaction flask to terminate the reaction. The mixture was filtered through celite and concentrated. The crude product was purified by silica gel column chromatography to obtain the glycosylated product. In some embodiments, any content with special instructions that differ from the standard operating procedures shall prevail.

[0158] Example 26: Synthesis of glycosylated product IV-04

[0159]

[0160] After S7 was synthesized according to the literature (Carbohydr. Res., 1993, 249, 221-241), S7 (970 mg, 1.81 mmol) was weighed in a round-bottom flask, and water was azeotroped with toluene twice, and then activated Molecular sieves. Anhydrous dichloromethane (3.7 mL) and benzyl mercaptan (255 μL, 2.17 mmol) were added under an argon atmosphere, cooled to 0°C, and a solution of boron trifluoride in ether (0.7 mL, 5.43 mmol) was slowly added. The mixture was reacted at 0°C for 24 hours. After the reaction was complete as monitored by TLC, the reaction system was diluted with ethyl acetate and washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution in sequence. The organic phase was dried over anhydrous sodium sulfate, filtered, and concentrated. The crude product was purified by silica gel column chromatography to obtain colorless syrup II-02 (950 mg, 84%). f =0.45(PE:EA=5:1).[α] D 25 =-41.3 (c = 1.0, in CHCl3). 1H NMR (400MHz, CDCl3) δ7.42-7.22(20H,m,Ar-H),5.52(1H,t,J=9.6Hz,H-2),4.99(1H,d,J=11.6Hz,-CH2Ph),4.70(1H,d,J =12.0Hz,-CH2Ph),4.62(1H,d,J=11.6Hz,-CH2Ph),4.56(1H,d,J=12.0Hz,-CH2Ph),4.52(1H,d,J=11.6Hz,-CH2Ph),4.47( 1H,d,J=11.6Hz,-CH2Ph),4.24(1H,d,J=9.6Hz,H-1),4.01(1H,d,J=2.4Hz,H-4),3.97(1H,d,J=12.8Hz,-CH2Ph),3.85(1 H,d,J=12.8Hz,-CH2Ph),3.67-3.61(2H,m),3.57(1H,t,J=6.0Hz),3.53(1H,dd,J=9.6,2.8Hz,H-3),2.05(3H,s,-COCH3). 13 C NMR (100MHz, CDCl3) δ169.9,138.7,138.2,138.0,1379,129.4,128.7,128.6,128.6,128.4,128.3,128.1,128.1,128 .0,127.7,127.6,127.1,82.7,81.7,77.7,74.7,73.8,73.3,72.3,69.8,68.8,33.5,21.2.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 36 H 38 NaO6S,621.2281; Found621.2296.

[0161]

[0162] According to the standard reaction procedure, glycosyl donor II-02 (36.7 mg, 0.061 mmol), glycosyl acceptor III-03 (25 mg, 0.051 mmol), activation reagent I-1 (6.5 mg, 0.015 mmol), DTBMP (12.6 mg, 0.061 mmol) and molecular sieves were added to the reaction flask, pre-cooled to 0°C and then Tf2O was added. After the reaction was complete, colorless syrup IV-04 (44.7 mg, 91%) was obtained after treatment. f =0.38(PE:EA=5:1). 1H NMR (400 MHz, CDC13) δ 7.36-7.24 (19H, m, Ar-H), 7.23-7.09 (6H, m, Ar-H), 5.35 (1H, dd, J = 10.0, 8.4 Hz, H-2'), 5.00-4.93 (2H, m, Bn-H), 4.77 (1H, d, J = 12.0 Hz, Bn-H), 4.73 (1H, d, J = 10.4 Hz, H-1'), 4.66 (1H, d, J = 12.4 Hz, Bn-H), 4.60 (1H, d, J = 11.6 Hz, Bn-H), 4.59 (1H, d, J = 3.2 Hz, H-1), 4.55-4.51 (2H, m, Bn-H), 4.45 (1H, d, J = 12.4 Hz, Bn-H), 4.30 (1H, d, J = 11.6 Hz, Bn-H), 4.20 (1H, d, J = 11.6 Hz, Bn-H), 3.96 (1H, d, J = 2.4 Hz, H-4'), 3.83 (1H, t, J = 9.2 Hz, H-3), 3.79-3.67 (3H, m), 3.53 (1H, t, J = 8.4 Hz, H-4), 3.50-3.44 (1H, m, H-5), 3.44-3.35 (3H, m), 3.34-3.28 (4H, m, -OMe), 2.00 (3H, s, -OAc), 0.84 (9H, s, -C(CH3)3), 0.00 (6H, s, -Si(CH3)2). 13 C NMR (100 MHz, CDC13) δ 169.5, 139.6, 139.0, 138.7, 138.2, 138.1, 128.6, 128.5, 128.4, 128.2, 128.1, 128.1, 128.1, 127.9, 127.9, 127.6, 127.2, 101.0, 98.3, 80.6, 80.1, 79.7, 75.6, 74.8, 73.7, 73.6, 73.5, 72.8, 72.2, 71.8, 71.2, 68.1, 61.5, 55.2, 26.1, 21.3, 18.4, -4.9, -5.2. HRMS (ESI-TOF) m / z: [M + Na] calcd for C + calcd for C 56 H 70 NaO 12 Si + , 985.4529; Found, 985.4538.

[0163] Example 27: Synthesis of glycosidation product IV-05

[0164]

[0165] After S8 was synthesized according to the literature (Org. Lett., 2010, 12, 2080-2083), the reference compound II-02 was prepared with S8 (356 mg, 0.66 mmol) as raw material, benzyl mercaptan (182 μL, 1.58 mmol, 5.0 equiv) under the condition of reaction for 1 h, TLC monitoring reaction complete, the reaction system was diluted with ethyl acetate, washed with water, saturated sodium bicarbonate, saturated sodium chloride solution. The organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, the crude product was purified by silica gel column chromatography to give colorless syrup II-03 (369 mg, 93%). α / β mixture, ratio of 4.5:1 (the same as the amount of substance ratio of the α configuration product to the β configuration product in the product, the same below). R f = 0.43 (PE:EA = 5:1). Main product (α): 1 H NMR (400 MHz, CDC13) δ 7.39-7.11 (20H, m, Ar-H), 5.38 (1H, d, J = 0.8 Hz, H-2), 5.16 (1H, s, H-1), 4.82 (1H, d, J = 10.8 Hz, -CH2Ph), 4.66 (1H, d, J = 12.0 Hz, -CH2Ph), 4.64 (1H, d, J = 10.8 Hz, -CH2Ph), 4.50-4.42 (3H, m, -CH2Ph), 4.16-4.09 (1H, m), 3.92-3.87 (2H, m), 3.80-3.69 (3H, m), 3.55 (1H, dd, J = 10.8, 1.6 Hz, H-3), 2.10 (3H, s, -COCH3). 13 C NMR (100 MHz, CDC13) δ 170.4, 138.5, 138.4, 137.9, 137.6, 129.2, 128.8, 128.6, 128.5, 128.4, 128.1, 128.0, 127.9, 127.4, 81.9, 79.0, 75.4, 74.7, 73.7, 72.1, 70.2, 68.9, 35.0, 21.3. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 36 H 38 NaO6S, 621.2281; Found 621.2273.

[0166]

[0167] According to the standard operation procedure of reaction, glycosyl donor II-03 (30.9 mg, 0.052 mmol), glycosyl acceptor III-04 (20.0 mg, 0.043 mmol), activating reagent I-1 (5.5 mg, 0.013 mmol) and molecular sieves were added into the reaction bottle, and the reaction bottle was pre-cooled to 0 °C before adding Tf20. After the reaction was completed, treatment was performed to obtain colorless syrup IV-05 (37.2 mg, 92%). f = 0.59 (PE:EA = 2:1). 1 H NMR (400 MHz, CDC13) δ 7.39-7.10 (30H, m, Ar-H), 5.47-5.45 (1H, m, H-2'), 4.95 (1H, d, J = 1.2 Hz, H-1'), 4.90 (1H, d, J = 11.2 Hz, Bn-H), 4.84 (1H, d, J = 10.8 Hz, Bn-H), 4.72-4.69 (3H, m, Bn-H, H-1), 4.64 (1H, d, J = 12.0 Hz, Bn-H), 4.64 (1H, d, J = 11.6 Hz, Bn-H), 4.61-4.55 (m, 2H, Bn-H), 4.48 (1H, d, J = 11.6 Hz, Bn-H), 4.46-4.40 (3H, m, Bn-H), 3.95 (1H, dd, J = 9.2, 3.2 Hz,), 3.92-3.83 (4H, m), 3.81-3.74 (2H, m), 3.72-3.64 (3H, m), 3.58 (1H, dd, J = 10.8, 1.2 Hz, H-3), 3.24 (3H, s, -OMe), 2.13 (3H, s, -OAc).

[0168] Example 28: Synthesis of glycosylation product IV-06

[0169]

[0170] After synthesizing S9 according to the literature (Carbohydr. Res., 1981, 93, 43-52), S9 (500 mg, 1.17 mmol) was used as the raw material according to the preparation method of compound II-02. After 12 hours of reaction, TLC was used to monitor the completion of the reaction. The reaction system was diluted with ethyl acetate, and then washed with water, saturated sodium bicarbonate solution and saturated sodium chloride solution. After the organic phase was dried over anhydrous sodium sulfate, it was filtered and concentrated. The crude product was purified by silica gel column chromatography to obtain yellow syrup II-04 (468 mg, 93%). α / β mixture, ratio 3.2:1. 1H NMR (400 MHz, CDC13) δ 7.35-7.25 (13H, m, Ar-H), 5.63 (0.31H, dd, J = 3.6, 1.2 Hz, H-2β), 5.42 (1H, dd, J = 3.6, 1.6 Hz, H-2α), 5.17 (1H, d, J = 1.2 Hz, H-1α), 4.90 (1.35H, d, J = 10.8 Hz, -CH2Ph), 4.75 (0.33H, d, J = 11.2 Hz, -CH2Ph), 4.66 (1H, d, J = 11.2 Hz, -CH2Ph), 4.63 (0.33H, d, J = 0.8 Hz, H-1β), 4.59 (1.35H, d, J = 10.8 Hz, -CH2Ph), 4.52-4.46 (1.35H, m, -CH2Ph), 4.07 (1H, dq, J = 9.6, 6.0 Hz, H-5α), 3.86 (1H, dd, J = 9.2, 3.6 Hz, H-3α), 3.62 (0.31H, dd, J = 8.8, 3.6 Hz, H-3β), 3.48-3.35 (1.7H, m, H-4), 2.71 (0.66H, qd, J = 7.6, 2.0 Hz, -SC H 2CH3β), 2.67-2.51 (2H, m, -SC H 2CH3α), 2.19 (0.9H, s, OAcβ), 2.14 (3H, s, OAcα), 1.36 (0.93H, d, J = 5.6 Hz, -CH3, H-6β), 1.32 (3H, d, J = 6.0 Hz, -CH 3, H-6α), 1.30-1.23 (3.9H, m, -SCH2C H 3).

[0171]

[0172] According to the standard operation procedure of reaction, glycosyl donor II-04 (25.8 mg, 0.06 mmol), glycosyl acceptor III-05 (18.6 mg, 0.05 mmol), activating reagent I-1 (6.5 mg, 0.015 mmol), DTBMP (12.3 mg, 0.06 mmol) and molecular sieves were added into the reaction vial, cooled to 0 °C before adding Tf20, reaction for 1 h, then warmed to 30 °C until the reaction was completed, after treatment, IV-06 (31.9 mg, 86%) was obtained as colorless syrup. Rf= 0.54 (PE:EA = 3:1). f 1 ​H NMR (400 MHz, CDC13) δ 7.47-7.42 (2H, m, Ar-H), 7.38-7.25 (15H, m, Ar-H), 7.24-7.19 (3H, m, Ar-H), 5.48 (1H, dd, J = 3.2, 1.6 Hz, H-2'), 5.47 (1H, s, -CHPh), 5.13 (1H, br s, H-1'), 4.82 (1H, d, J = 10.8 Hz, Bn-H), 4.75 (1H, d, J = 12.0 Hz, Bn-H), 4.71 (1H, d, J = 11.2 Hz, Bn-H), 4.56 (1H, d, J = 12.0 Hz, Bn-H), 4.54-4.50 (3H, m, Bn-H, H-1), 4.23 (1H, dd, J = 10.0, 4.8 Hz, H-3'), 4.16-4.04 (2H, m), 3.91 (1H, dd, J = 9.2, 3.2 Hz), 3.80 (1H, td, J = 10.0, 4.4 Hz), 3.66 (1H, t, J = 10.4 Hz), 3.49 (1H, dd, J = 9.2, 3.6 Hz, H-2), 3.43 (1H, t, J = 9.6 Hz), 3.37-3.31 (4H, m), 2.10 (3H, s, -OMe), 0.92 (3H, d, J = 6.4 Hz, -CHCH3), 0.90 (3H, d, J = 6.4 Hz, -CHCH3). H 3). 13 C NMR (100 MHz, CDC13) δ 170.4, 139.0, 138.5, 137.9, 137.3, 129.1, 128.7, 128.6, 128.5, 128.4, 128.3, 128.3, 128.2, 127.9, 127.8, 127.7, 126.5, 101.9, 98.8, 98.6, 80.5, 80.1, 78.3, 75.2, 74.5, 73.5, 72.0, 69.2, 67.6, 62.7, 55.5, 21.3, 17.6. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 43 H 48 NaO 11 + ,763.3089; Found, 763.3103.

[0173] Example 29: Synthesis of glycosidation product IV-07

[0174]

[0175] According to the standard procedure of reaction, glycosyl donor II-04 (25.8 mg, 0.06 mmol), glycosyl acceptor III-06 (23.0 mg, 0.05 mmol), activating reagent I-1 (6.5 mg, 0.015 mmol), DTBMP (12.3 mg, 0.06 mmol) and molecular sieves were added into the reaction vial, after pre-cooling to 0 °C, Tf20 was added, after 1 h of reaction, IV-07 (35.5 mg, 86%) was obtained as colorless syrup after workup. R f = 0.15 (PE:EA = 3:1). 1 H NMR (400 MHz, CDC13) δ 7.34-7.22 (17H, m, Ar-H), 7.19-7.14 (3H, m, Ar-H), 5.20 (1H, br s, H-2'), 4.99 (2H, s, Bn-H), 4.90 (1H, s, H-1'), 4.89-4.83 (2H, m), 4.69 (1H, d, J = 10.8 Hz, Bn-H), 4.64-4.56 (3H, m), 4.53 (1H, d, J = 10.8 Hz, Bn-H), 4.48 (1H, d, J = 11.6 Hz, Bn-H), 4.41 (1H, d, J = 12.0 Hz, Bn-H), 4.10 (1H, dd, J = 12.0, 3.2 Hz, H-2), 4.00 (1H, td, J = 10.0, 3.2 Hz), 3.89 (1H, dd, J = 9.2, 6.4 Hz), 3.84 (1H, dd, J = 9.2, 3.2 Hz), 3.80-3.68 (2H, m), 3.55 (1H, t, J = 9.6 Hz), 3.35 (1H, t, J = 9.6 Hz), 3.30 (3H, s, -OMe), 2.08 (3H, s, -OAc), 2.08 (3H, s, -OAc), 1.02 (3H, d, J = 6.0 Hz). 13 C NMR (100 MHz, CDC13) δ 170.9, 170.6, 156.0, 138.8, 138.2, 138.0, 136.4, 128.7, 128.6, 128.5, 128.4, 128.4, 128.3, 128.2, 128.0, 127.9, 127.8, 127.7, 99.1, 98.4, 80.1, 79.7, 77.7, 75.7, 75.5, 75.3, 71.8, 69.2, 69.1, 68.9, 67.2, 62.7, 55.5, 55.0, 21.3, 21.0, 18.0. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 46 H 53 NNaO13 + Found, 850.3390.

[0176] Example 30: Synthesis of glycosylation product IV-08

[0177]

[0178] According to the standard procedure of reaction, glycosyl donor II-12 (38.3 mg, 0.08 mmol), glycosyl acceptor III-07 (21.3 mg, 0.067 mmol), activating reagent I-1 (17.2 mg, 0.04 mmol), and molecular sieves were added into the reaction vial, after pre-cooling to 0 °C, Tf20 was added, after 1 h of reaction, IV-08 (45.7 mg, 93%) was obtained as colorless syrup after workup. Rf = 0.24 (PE:EA = 2:1). f 1 H NMR (400 MHz, CDC13) δ 7.81 (2H, dd, J = 5.2, 3.2 Hz, Ar-H), 7.74-7.68 (2H, m, Ar-H), 5.73 (1H, dd, J = 10.8, 9.2 Hz), 5.37 (1H, d, J = 8.4 Hz, H-1'), 5.29 (1H, t, J = 10.0 Hz), 5.13 (1H, t, J = 9.6 Hz), 4.71 (1H, t, J = 10.0 Hz), 4.64 (1H, dd, J = 10.0, 3.6 Hz, H-2), 4.41 (1H, d, J = 3.6 Hz, H-1), 4.34-4.26 (2H, m), 4.13 (1H, dd, J = 12.0, 2.0 Hz), 3.87 (1H, dd, J = 10.4, 1.6 Hz), 3.85-3.76 (2H, m), 3.44 (1H, dd, J = 10.8, 7.2 Hz), 2.98 (3H, s, -COCH3), 2.08 (3H, s, -COCH3), 1.99 (3H, s, -COCH3), 1.97 (3H, s, -COCH3), 1.89 (3H, s, -COCH3), 1.88 (3H, s, -COCH3), 1.83 (3H, s, -COCH3).

[0179] Example 31: Synthesis of glycosylation product IV-09

[0180]

[0181] ​According to the standard procedure of reaction, glycosyl donor II-13 (23.3 mg, 0.059 mmol), glycosyl acceptor III-08 (23.0 mg, 0.049 mmol), activating reagent I-1 (12.5 mg, 0.029 mmol), and molecular sieves were added into a reaction vial, pre-cooled to 0 °C, followed by the addition of Tf20. After 1 h of reaction, work-up afforded IV-09 (36.3 mg, 92%) as colorless syrup. Rf = 0.23 (PE:acetone = 4:1). f = 0.23 (PE:acetone = 4:1). 1 H NMR (400 MHz, CDC13) δ 7.37 - 7.26 (9H, m, Ar-H), 7.26 - 7.21 (4H, m, Ar-H), 7.14 (2H, dd, J = 7.6, 2.0 Hz, Ar-H), 5.44 (1H, dd, J = 3.6, 2.0 Hz, H-2'), 5.39 (1H, dd, J = 10.0, 3.6 Hz, H-3'), 5.23 (1H, t, J = 10.0 Hz, H-4'), 4.95 (1H, d, J = 1.6 Hz, H-1'), 4.81 (1H, d, J = 10.8 Hz, Bn-H), 4.77 (1H, d, J = 2.0 Hz, H-1), 4.69 (1H, d, J = 11.6 Hz, Bn-H), 4.65 - 4.58 (2H, m, Bn-H), 4.56 (1H, d, J = 12.4 Hz, Bn-H), 4.48 (1H, d, J = 10.8 Hz, Bn-H), 4.22 (1H, dd, J = 12.0, 5.6 Hz, H-6'a), 4.19 - 4.14 (1H, m, H-5'), 4.09 (1H, dd, J = 12.0, 2.0 Hz, H-6'b), 3.93 (1H, t, J = 2.4 Hz, H-2), 3.90 - 3.81 (2H, m,), 3.75 - 3.68 (3H, m), 3.33 (3H, s, OMe), 2.09 (3H, s, -COCH3), 2.07 (3H, s, -COCH3), 1.98 (3H, s, -COCH3), 1.97 (3H, s, -COCH3).

[0182] Example 32: Synthesis of glycosylation product IV-10

[0183]

[0184] According to the standard procedure of reaction, glycosyl donor II-14 (36.3 mg, 0.082 mmol), glycosyl acceptor III-09 (25.0 mg, 0.068 mmol), activating reagent I-1 (17.4 mg, 0.041 mmol), DTBMP (16.8 mg, 0.082 mmol) and molecular sieves were added into the reaction vial, after pre-cooling to 0 °C, Tf20 was added, after 1 h of reaction, work-up afforded colorless syrup IV-10 (30.5 mg, 64%). R f = 0.30 (PE:EA = 3:1). 1 H NMR (400 MHz, CDC13) δ 7.43 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.36 (1H, dd, J = 7.6, 1.6 Hz, Ar-H), 7.26 (1H, dd, J = 7.2, 1.6 Hz, Ar-H), 7.23-7.18 (1H, m, Ar-H), 5.35 (1H, d, J = 2.8 Hz, H-4'), 5.11 (1H, dd, J = 10.4, 8.0 Hz, H-2'), 5.06-5.00 (2H, m, H-1, H-3'), 4.87 (1H, d, J = 7.6 Hz, H-1'), 4.83 (1H, d, J = 12.0 Hz, -CH2Ar), 4.60 (1H, d, J = 12.0 Hz, -CH2Ar), 4.14-4.04 (4H, m), 3.86 (1H, t, J = 6.4 Hz), 3.73 (1H, dq, J = 12.4, 6.4 Hz, H-5), 3.51 (1H, dd, J = 10.0, 7.2 Hz), 3.35 (1H, hept, J = 6.8 Hz, -CH(CH3)2), 2.13 (3H, s, -COCH3), 2.04 (3H, s, -COCH3), 2.01 (3H, s, -COCH3), 1.96 (3H, s, -COCH3), 1.50 (3H, s, -C(CH3)2), 1.31 (3H, s, -C(CH3)2), 1.29-1.24 (m, 9H, -CHCH3, -CH(CH3)2). 13 C NMR δ 170.6, 170.5, 170.4, 167.0, 138.4, 135.7, 132.6, 129.7, 128.7, 127.0, 109.4, 100.8, 96.4, 80.7, 78.3, 76.3, 71.1, 70.9, 69.3, 67.8, 67.4, 64.5, 61.8, 38.8, 28.2, 26.6, 23.3, 23.3, 21.1, 20.90, 20.85, 20.8, 17.7. HRMS (ESI-TOF) m / z: [M+Na] +C 33 H 46 NaO 14 S + ,721.2500; Found, 721.2481.

[0185] Example 33: Synthesis of glycosylation product IV-11

[0186]

[0187] According to the standard procedure of reaction, glycosyl donor II-16 (22.5 mg, 0.039 mmol), glycosyl acceptor III-10 (15 mg, 0.032 mmol), activating reagent I-1 (8.2 mg, 0.019 mmol), and molecular sieves were added into the reaction vial, pre-cooled to -40 °C, followed by the addition of Tf20. After 3 h of reaction, the reaction mixture was worked up to give compound IV-11 (18.5 mg, 62%) as colorless syrup. Rf = 0.11 (PE-Acetone = 3:1). f = 0.11 (PE-Acetone = 3:1). 1 H NMR (400 MHz, CDC13) δ 7.35-7.25 (15H, m, Ar-H), 5.52 (1H, dd, J = 8.8, 1.6 Hz), 5.42-5.37 (1H, m), 4.90 (1H, d, J = 10.8 Hz), 4.80-4.72 (4H, m), 4.64 (1H, d, J = 12.0 Hz), 4.63 (1H, dd, J = 9.2, 2.0 Hz), 4.59 (1H, d, J = 3.6 Hz, H-1), 4.42-4.15 (2H, m), 3.98-3.91 (2H, m), 3.84 (1H, d, J = 12.4, 6.4 Hz), 3.77-3.73 (1H, m), 3.68 (3H, s), 3.61 (1H, dd, J = 11.2, 9.2 Hz), 3.53 (1H, dd, J = 10.0, 8.8 Hz), 3.50 (1H, dd, J = 10.0, 3.6 Hz), 3.45 (1H, dd, J = 10.8, 2.0 Hz), 3.35 (3H, s), 2.89 (1H, dd, J = 12.0, 3.6 Hz), 2.09 (3H, s), 2.07 (1H, dd, J = 13.6, 12.0 Hz), 1.99 (3H, s), 1.74 (3H, s).

[0188] Example 34: Synthesis of glycosylation product IV-12

[0189]

[0190] According to the standard procedure of reaction, glycosyl donor II-04 (41.4 mg, 0.096 mmol), glycosyl acceptor III-11 (15.0 mg, 0.04 mmol), activating reagent I-1 (10.2 mg, 0.024 mmol), DTBMP (19.7 mg, 0.096 mmol) and molecular sieves were added into the reaction vial, cooled to 0 °C before adding Tf20, the reaction was allowed to warm to 30 °C until completion, work-up to get IV-12 (33.4 mg, 75%) as colorless syrup. R f = 0.30 (PE:EA = 3:1). 1 H NMR (400 MHz, CDC13) δ 7.36 - 7.25 (26H, m, Ar-H), 7.24 - 7.19 (4H, m, Ar-H), 5.26 (1H, dd, J = 3.2, 1.6 Hz), 5.12 (1H, dd, J = 3.2, 1.6 Hz), 5.01 (1H, d, J = 10.8 Hz, Bn-H), 4.89 (1H, d, J = 4.4 Hz, H-1), 4.88 - 4.85 (2H, m), 4.76 (1H, d, J = 1.2 Hz), 4.70 (1H, d, J = 5.6 Hz), 4.69 - 4.61 (3H, m, Bn-H), 4.61 - 4.54 (3H, m, Bn-H), 4.54 - 4.48 (3H, m, Bn-H), 3.96 - 3.83 (3H, m), 3.83 - 3.72 (3H, m), 3.66 - 3.62 (2H, m), 3.60 - 3.55 (1H, m), 3.48 (1H, dd, J = 9.2, 3.6 Hz), 3.39 (2H, td, J = 9.6, 3.2 Hz, H-5), 3.31 (3H, s, -OMe), 2.11 (3H, s, -COCH3), 2.10 (3H, s, -COCH3), 1.29 (3H, d, J = 6.4 Hz, -CHCH3), 0.92 (3H, d, J = 6.4 Hz, -CHCH3). H 3), 0.92 (3H, d, J = 6.4 Hz, -CHCH3). H 3). 13C NMR (100 MHz, CDC13) δ 171.1, 170.2, 138.9, 138.8, 138.6, 138.23, 138.16, 138.1, 128.7, 128.6, 128.6, 128.6, 128.5, 128.4, 128.4, 128.4, 128.4, 128.1, 128.0, 127.9, 127.7, 127.5, 97.8, 97.7, 97.6, 80.8, 80.4, 80.3, 79.8, 77.7, 75.8, 75.7, 75.5, 75.5, 73.5, 72.0, 71.7, 69.8, 69.7, 68.9, 68.5, 67.8, 65.7, 55.4, 21.3, 21.2, 18.1, 17.8. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 65 H 74 NaO 16 + , 1133.4869; Found, 1133.4875.

[0191] Example 35: Synthesis of glycosidation product IV-13

[0192]

[0193] According to the standard procedure of reaction, glycosyl donor II-15 (42.0 mg, 0.06 mmol), glycosyl acceptor III-12 (20.8 mg, 0.05 mmol), activating reagent I-1 (12.8 mg, 0.03 mmol), and molecular sieves were added into the reaction vial, pre-cooled to 0 °C, then Tf20 was added, after 1 h of reaction, the white solid IV-13 (29.9 mg, 60%) was obtained after workup. Rf= 0.45 (PE:EA = 3:1). f 1 ​HNMR (400 MHz, CDC13) δ 8.01-7.96 (2H, m, Ar-H), 7.93-7.87 (4H, m, Ar-H), 7.84-7.73 (4H, m, Ar-H), 7.54-7.21 (23H, m, Ar-H), 5.87 (1H, t, J = 10.0 Hz, H-4), 5.63 (1H, t, J = 9.6 Hz, H-3), 5.59 (1H, d, J = 8.0 Hz, H-1), 5.46 (1H, dd, J = 9.6, 8.0 Hz, H-2), 5.15 (1H, d, J = 12.4 Hz, Bn-H), 5.10 (1H, d, J = 12.4 Hz, Bn-H), 4.74 (1H, d, J = 7.8 Hz, -NH), 4.60 (1H, dd, J = 12.0, 3.2 Hz, H-6a), 4.52-4.48 (1H, m, H-5), 4.41 (1H, dd, J = 12.0, 5.2 Hz, H-6b), 4.37-4.28 (2H, m), 4.19 (1H, dd, J = 10.4, 7.2 Hz), 4.11-4.02 (2H, m), 3.89 (1H, dd, J = 10.4, 3.2 Hz). 13 C NMR (100 MHz, CDC13) δ 169.5, 166.3, 166.0, 165.4 165.3, 156.1, 144.0, 143.9, 141.5, 141.5, 135.4, 133.7, 133.5, 133.5, 133.4, 130.0, 130.0, 130.0, 129.7, 129.3, 129.0, 128.9, 128.8, 128.6, 128.6, 128.5, 128.4, 127.9, 127.9, 127.3, 125.4, 125.3, 120.2, 120.2, 101.6, 72.8, 72.5, 72.0, 69.7, 67.7, 67.2, 63.2, 54.6, 47.3. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 59 H 49 NNaO 14 + , 1018.3045; Found, 1018.3022.

[0194] Example 36: Synthesis of glycosidation product IV-14

[0195]

[0196] According to the standard procedure of reaction, glycosyl donor II-01 (34.4 mg, 0.058 mmol), glycosyl acceptor III-13 (20.0 mg, 0.048 mmol), activating reagent I-1 (6.1 mg, 0.014 mmol), and molecular sieves were added into a reaction vial, cooled to 0 °C before the addition of Tf20, the reaction was allowed to proceed for 1 h before workup to give white solid IV-14 (39.6 mg, 85%). Rf= 0.27 (PE:EA = 3:1). Melting point: 113.0-114.0 °C. f = 0.27 (PE:EA = 3:1). Melting point: 113.0-114.0 °C. 1 H NMR (400 MHz, CDC13) δ 7.74 (2H, d, J = 7.6 Hz, Ar-H), 7.62 (2H, t, J = 8.0 Hz, Ar-H), 7.38 (2H, t, J = 7.2 Hz, Ar-H), 7.34 - 7.25 (15H, m, Ar-H), 7.20 - 7.13 (2H, m, Ar-H), 5.74 (1H, d, J = 9.2 Hz, -NH), 4.92 (1H, t, J = 8.4 Hz, H-2), 4.78 (1H, d, J = 11.6 Hz, -CH2Ph), 4.77 (1H, d, J = 10.4 Hz, -CH2Ph), 4.66 (1H, d, J = 11.2 Hz, -CH2Ph), 4.55 (2H, d, J = 12.0 Hz, -CH2Ph), 4.49 (1H, d, J = 12.0 Hz, -CH2Ph), 4.41 - 4.29 (5H, m), 4.22 (1H, t, J = 7.2 Hz), 3.76 - 3.58 (7H, m), 3.40 (1H, dt, J = 4.2, 2.4 Hz), 1.94 (3H, s, -COCH3), 1.18 (3H, d, J = 6.4 Hz, -CHCH3), 1.17 (3H, d, J = 6.8 Hz, -CHCH3). H 3).

[0197] Example 37: Synthesis of glycosylation product IV-15

[0198]

[0199] According to the standard procedure of reaction, glycosyl donor II-01 (50.1 mg, 0.084 mmol), glycosyl acceptor III-14 (20 mg, 0.07 mmol), activating reagent I-1 (9.0 mg, 0.021 mmol), DTBMP (17.2 mg, 0.084 mmol), and molecular sieves were added into a reaction vial, cooled to 0 °C before the addition of Tf20, the reaction was allowed to proceed for 1 h before warming to 30 °C until complete, workup to give colorless syrup IV-15 (40.0 mg, 75%). Rf= 0.40 (PE:EA = 12:1). f = 0.40 (PE:EA = 12:1). 1H NMR (400 MHz, CDC13) δ 7.33-7.25 (13H, m, Ar-H), 7.19 (2H, dd, J = 7.6, 2.0 Hz, Ar-H), 4.94 (1H, t, J = 8.8 Hz, H-2), 4.77 (2H, d, J = 11.2 Hz, Bn-H), 4.64 (1H, d, J = 12.0 Hz, Bn-H), 4.61 (1H, d, J = 12.4 Hz, Bn-H), 4.57 (1H, d, J = 9.6 Hz, Bn-H), 4.54 (1H, d, J = 12.4 Hz, Bn-H), 4.34 (1H, d, J = 8.0 Hz, H-1), 3.72-3.60 (7H, m), 3.51-3.47 (1H, m), 3.47-3.41 (1H, m, H-5), 2.28 (2H, t, J = 7.6 Hz, -COCH2-), 1.92 (3H, s, -COCH3), 1.65-1.52 (3H, m), 1.50-1.12 (24H, m). 13 C NMR (100 MHz, CDC13) δ 174.5, 169.6, 138.5, 138.5, 138.2, 128.6, 128.6, 128.6, 128.3, 128.1, 127.9, 127.8, 127.7, 101.0, 83.4, 81.0, 78.4, 75.4, 75.2, 75.2, 73.8, 73.7, 69.3, 51.7, 35.0, 34.4, 34.3, 32.2, 30.1, 29.8, 29.7, 29.5, 29.3, 25.2, 25.2, 22.9, 21.2, 14.3. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 46 H 64 NaO9 + ,783.4443; Found, 783.4499.

[0200] Example 38: Synthesis of glycosidation product IV-16

[0201]

[0202] According to the standard procedure of reaction, glycosyl donor II-01 (22.9 mg, 0.038 mmol), glycosyl acceptor III-15 (20.0 mg, 0.032 mmol), activating reagent I-1 (4.1 mg, 0.01 mmol), DTBMP (7.9 mg, 0.038 mmol) and 4A MS were added into the reaction vial, after pre-cooling to 0 oC, Tf20 was added, after 1 h reaction, the reaction mixture was worked up to give IV-16 (28.0 mg, 80%) as colorless syrup. Rf = 0.60 (PE:EA = 3:1). [a] f = 0.60 (PE:EA = 3:1). [a] D 25 + 14.5 (c, 1.0 in CHCI3). 1 H NMR (400 MHz, CDCI3) d 7.36 - 7.10 (18H, m, Ar-H), 6.55 (1H, d, J = 2.0 Hz, Ar-H), 6.50 (1H, d, J = 2.0 Hz, Ar-H), 4.92 (1H, dd, J = 9.2, 8.0 Hz, H-2), 4.82 (1H, d, J = 8.8 Hz, H-1), 4.75 (1H, d, J = 10.8 Hz, Bn-H), 4.74 (1H, d, J = 11.6 Hz, -CH2Ph), 4.62 (1H, d, J = 12.0 Hz, Bn-H), 4.61 (1H, d, J = 11.2 Hz, Bn-H), 4.53 (1H, d, J = 12.4 Hz, Bn-H), 4.52 (1H, d, J = 10.4 Hz), 4.12 - 4.04 (2H, m), 3.74 - 3.66 (3H, m), 3.55 (1H, t, J = 9.2 Hz, H-4), 3.42 (1H, dt, J = 9.6, 2.8 Hz, H-5), 3.08 (1H, dd, J = 16.8, 6.0 Hz), 2.78 (1H, dd, J = 16.8, 9.2 Hz), 1.84 (3H, s, -COCH3), 1.37 (9H, s, -OPiv), 1.37 (9H, s, -OPiv), 1.34 (18H, s, -OPiv). 13C NMR (100MHz, CDCl3) δ176.9,176.3,175.8,169.8,155.0,150.3,149.8,143.0,142.9,138.4 ,138.2,138.2,136.7,128.61,128.58,128.1,128.0,127.9,127.8,126.0,123.4,122.3,11 1.7,108.8,107.5,100.7,83.1,79.2,77.9,75.2,75.1,75.0,74.2,73.6,73.0,69.0,39.5, 39.4,39.3,39.3,29.6,28.4,27.5,27.5,27.4,27.3,23.0,21.0.HRMS(ESI-TOF)m / z:[M+Na] + calcd for C 64 H 76 NaO 16 + ,1123.5026;Found,1123.5064.

[0203] Example 39: Synthesis of glycosylated product IV-17

[0204]

[0205] According to the standard reaction procedure, glycosyl donor II-02 (45.9 mg, 0.077 mmol), glycosyl acceptor III-16 (10.0 mg, 0.064 mmol), activation reagent I-1 (8.2 mg, 0.019 mmol), and molecular sieves were added to the reaction flask, pre-cooled to 0°C, and Tf2O was added. After reacting for 1 hour, colorless syrup IV-17 (36.7 mg, 91%) was obtained. f =0.31(PE:EA=10:1). 1H NMR (400 MHz, CDC13) δ 7.40-7.24 (15H, m, Ar-H), 5.25 (1H, dd, J = 10.0, 8.0 Hz, H-2), 4.92 (1H, d, J = 12.0 Hz, Bn-H), 4.64 (1H, d, J = 12.4 Hz, Bn-H), 4.59 (1H, d, J = 11.6 Hz, Bn-H), 4.49 (1H, d, J = 12.0 Hz, Bn-H), 4.44 (1H, d, J = 11.6 Hz, Bn-H), 4.39 (1H, d, J = 12.0 Hz, Bn-H), 4.33 (1H, d, J = 8.0 Hz, H-1), 3.91 (1H, d, J = 2.4 Hz, H-4), 3.64-3.46 (4H, m), 3.30 (1H, td, J = 10.8, 4.4 Hz, -OCH-), 2.36-2.27 (1H, m), 2.01 (3H, s, -COCH3), 1.94-1.86 (1H, m), 1.62-1.55 (2H, m), 1.33-1.24 (1H, m), 1.22-1.11 (1H, m), 0.95-0.86 (4H, m), 0.85-0.75 (5H, m), 0.70 (3H, d, J = 7.2 Hz, -CH3).

[0206] Example 40: Synthesis of glycosidation product IV-18

[0207]

[0208] According to the standard procedure of reaction, glycosyl donor II-03 (47.2 mg, 0.079 mmol), glycosyl acceptor III-17 (10.0 mg, 0.067 mmol), activating reagent I-1 (8.6 mg, 0.020 mmol), and molecular sieves were added into the reaction vial, pre-cooled to 0 °C, then Tf20 was added, after 1 h of reaction, the compound IV-18 (33.3 mg, 80%) was obtained as yellow syrup after workup. f = 0.64 (PE:EA = 5:1). 1H NMR (400 MHz, CDC13) δ 7.35-7.19 (13H, m, Ar-H), 7.15-7.11 (2H, m, Ar-H), 5.24 (1H, d, J = 1.6 Hz, H-1), 5.15 (1H, dd, J = 3.2, 2.4 Hz, H-2), 4.83 (1H, d, J = 10.4 Hz, Bn-H), 4.68 (2H, d, J = 11.6 Hz, Bn-H), 4.52 (1H, d, J = 11.2 Hz, Bn-H), 4.45 (1H, d, J = 12.0 Hz, Bn-H), 4.43 (1H, d, J = 10.8 Hz, Bn-H), 4.03 (1H, dd, J = 9.2, 3.2 Hz, H-3), 4.00 - 3.96 (1H, m, H-5), 3.88 (1H, t, J = 9.6 Hz, H-4), 3.80 (1H, dd, J = 10.8, 4.0 Hz, H-6a), 3.65 (1H, dd, J = 10.8, 1.6 Hz, H-6b), 2.12 (s, 3H), 2.09 (3H, brs), 1.80 - 1.70 (6H, m), 1.62 - 1.50 (6H, m). 13 C NMR (100 MHz, CDC13) δ 171.0, 138.6, 138.5, 138.3, 128.6, 128.5, 128.4, 128.3, 128.2, 127.9, 127.9, 127.8, 127.7, 91.2, 78.4, 75.4, 75.2, 74.8, 73.6, 71.9, 71.1, 70.6, 69.2, 42.5, 36.4, 30.8, 21.5.

[0209] Example 41: Synthesis of glycosidation product IV-19

[0210]

[0211] According to the standard procedure of reaction, glycosyl donor II-17 (25.3 mg, 0.044 mmol), glycosyl acceptor III-18 (7 mg, 0.037 mmol), activating reagent I-1 (4.7 mg, 0.011 mmol) and molecular sieves were added into the reaction vial, pre-cooled to 0 °C, then Tf20 was added, the reaction was warmed to 30 °C until completion, after 1 h, treated to give compound IV-19 (19.7 mg, 84%) as colorless syrup. 1H NMR (400 MHz, CDC13) δ 8.26 (1H, s, H-8), 8.05-8.80 (4H, m, Ar-H), 7.92-7.90 (2H, m, Ar-H), 7.61-7.52 (3H, m, Ar-H), 7.46-7.34 (6H, m, Ar-H), 6.46 (1H, d, J = 5.2 Hz, H-1'), 6.16 (1H, t, J = 5.6 Hz), 6.11 (1H, dd, J = 5.6, 4.0 Hz), 4.90 (1H, dd, J = 12.0, 3.2 Hz), 4.85 (1H, dd, J = 7.6, 4.0 Hz), 4.71 (1H, dd, J = 12.0, 4.0 Hz).

[0212] Example 42: Synthesis of glycosidation product V-1

[0213]

[0214] Glycosyl donor II-01 (35.9 mg, 0.060 mmol), activated reagent I-1 (12.8 mg, 0.030 mmol) were co-evaporated twice with toluene to remove water in a round bottom flask, then activated reagent I-1 was added. Anhydrous dichloromethane (0.5 mL) was added under argon atmosphere, cooled to -40 °C and stirred for 10 min, Tf20 (10.7 μL, 0.065 mmol) was added. The reaction was carried out at -40 °C for 5 min, then a solution of thio-glycosyl acceptor III-19 (29.2 mg, 0.05 mmol) and DTBMP (15.4 mg, 0.075 mmol) in dichloromethane (0.5 mL) was added dropwise, and the reaction was carried out for 15 min. A solution of acceptor III-02 (27.9 mg, 0.060 mmol) in dichloromethane (0.5 mL) was added to the above flask, and the reaction was carried out at 30 °C for 24 h. Finally, triethylamine (0.1 mL) was added to terminate the reaction, and the mixture was filtered, concentrated, and purified by column chromatography to give the white foamy target trisaccharide V-1 (50.6 mg, 73%). Rf = 0.35 (PE:acetone = 3:1). f 1 ​H NMR (400 MHz, CDC13) δ 7.86-7.81 (2H, m, Ar-H), 7.54 (1H, t, J = 7.2 Hz, Ar-H), 7.38 (2H, t, J = 7.6 Hz, Ar-H), 7.35-7.13 (35H, m, Ar-H), 7.08-6.89 (5H, m, Ar-H), 5.14 (1H, t, J = 8.4 Hz, H-2”), 5.06 (1H, d, J = 11.6 Hz, -CH2Ph), 4.99 (1H, t, J = 9.2 Hz, H-2’), 4.91 (1H, d, J = 12.0 Hz, -CH2Ph), 4.80-4.68 (4H, m), 4.63-4.51 (5H, m), 4.49 (1H, d, J = 3.6 Hz, H-1), 4.48-4.40 (3H, m), 4.35 (2H, s, -CH2Ph), 4.28 (1H, d, J = 12.0 Hz, -CH2Ph), 4.18 (1H, d, J = 12.0 Hz, -CH2Ph), 4.01 (1H, t, J = 9.2 Hz), 3.86-3.75 (2H, m), 3.75-3.63 (2H, m), 3.60-3.51 (3H, m), 3.51-3.36 (5H, m), 3.33 (1H, d, J = 10.8 Hz), 3.30-3.21 (4H, m), 3.10 (1H, d, J = 9.6 Hz), 1.89 (3H, s, -OAc). 13 C NMR (100 MHz, CDC13) δ 169.5, 165.0, 139.9, 138.9, 138.5, 138.5, 138.4, 138.4, 138.2, 138.0, 133.2, 130.1, 130.0, 128.8, 128.6, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.2, 128.1, 128.1, 128.0, 127.9, 127.9, 127.8, 127.7, 127.6, 127.5, 127.2, 127.1, 100.7, 100.4, 98.5, 83.1, 80.5, 80.4, 79.0, 78.2, 75.5, 75.3, 75.3, 75.1, 74.6, 73.9, 73.7, 73.7, 73.5, 73.5, 69.7, 68.8, 67.9, 67.8, 55.4, 21.1. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 84 H 88 NaO 18 +: Found: 1407.5863, Found: 1407.5899.

[0215] Example 43: Synthesis of glycosidation product V-2

[0216]

[0217] The synthesis of reference compound V-1 was performed with glycosyl donor II-01 (35.9 mg, 0.060 mmol), thioglycosyl acceptor III-20 (24.4 mg, 0.050 mmol) and acceptor III-02 (27.9 mg, 0.060 mmol) as starting materials to give V-2 as a white foamy material (48.0 mg, 71 %). Rf = 0.37 (PE:EA = 3:1). [a] f = 0.37 (PE:EA = 3:1). [a] D 25 +6.5 (c, 1.0 in CHCI3). 1 H NMR (400 MHz, CDCI3) δ 7.88 (2H, d, J = 8.0 Hz, Ar-H), 7.78 (2H, d, J = 8.0 Hz, Ar-H), 7.54-7.44 (6H, m, Ar-H), 7.44-7.32 (8H, m, Ar-H), 7.32-7.20 (15H, m, Ar-H), 7.19-7.10 (7H, m, Ar-H), 5.42 (1H, t, J = 9.6 Hz, H-3'), 5.33 (1H, dd, J = 9.2, 8.4 Hz, H-2'), 5.07 (1H, t, J = 9.6 Hz, H-4'), 5.01-4.95 (2H, m, H-2", -CH2Ph), 4.76-4.66 (6H, m, H-1', H-1"), 4.62-4.55 (4H, m, H-1), 4.53 (1H, d, J = 10.0 Hz, -CH2Ph), 4.50 (1H, d, J = 11.2 Hz), 4.44 (1H, d, J = 12.0 Hz, -CH2Ph), 4.33 (1H, d, J = 12.0 Hz, -CH2Ph), 3.97 (1H, t, J = 9.6 Hz), 3.83-3.74 (2H, m), 3.71 (1H, d, J = 9.2 Hz), 3.67-3.54 (4H, m), 3.53-3.44 (3H, m, H-2), 3.41 (1H, d, J = 10.8 Hz), 3.36 (1H, d, J = 10.8 Hz), 3.24 (3H, s, -OCH3), 2.82-2.76 (1H, m, H-5), 2.04 (3H, s, -COCH3), 1.94 (3H, s, -COCH3). 13C NMR (100 MHz, CDC13) δ 170.1, 170.0, 165.8, 164.9, 139.5, 138.5, 138.4, 138.3, 137.6, 133.5, 133.5, 130.0, 129.9, 129.2, 129.2, 129.1, 128.9, 128.7, 128.6, 128.6, 128.6, 128.5, 128.5, 128.4, 128.0, 127.9, 127.9, 127.9, 127.8, 127.8, 127.7, 127.6, 100.7, 99.9, 98.6, 83.2, 80.8, 80.1, 76.4, 74.7, 74.5, 74.4, 73.94, 73.9, 73.7, 73.5, 73.2, 72.3, 69.8, 69.7, 68.4, 67.6, 67.4, 55.5, 21.3, 20.8. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 79 H 82 NaO 20 + : 1373.5292, Found: 1373.5269.

[0218] The above examples are only examples, and the symmetrical disulfide compound containing a sulfoxide group obtained by the present application can be other compounds satisfying the structural general formula (I) in addition to the compounds shown in structural formula I-1 to structural formula I-6; for example, the symmetrical disulfide compound containing a sulfoxide group shown in the structural general formula (I) is used as an activating agent in the application of glycosylation reaction, and the reaction temperature of the glycosylation reaction can be -40°C to 30°C, for example, -40°C, -20°C, 0°C, 30°C, or any interval range consisting of these temperature values.

[0219] Those skilled in the art will readily understand that the above description is only preferred embodiments of the present application, and is not intended to limit the present application, and any modifications, equivalent replacements and improvements made within the spirit and principles of the present application shall be included in the protection scope of the present application.

Claims

1. A symmetrical disulfide compound containing a sulfoxide group, characterized in that, The structural general formula is shown as formula (I): Wherein, O is oxygen atom; S is sulfur atom; R is selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl; Ar is substituted or unsubstituted aromatic ring.

2. The symmetrical disulfide compound containing a sulfoxide group according to claim 1, wherein R is selected from substituted or unsubstituted C 1～20 alkyl, substituted or unsubstituted C 6～10 aryl; wherein the substituents are one or more, independently selected from C 1～20 alkyl, C 1～20 alkoxy; Ar is substituted or unsubstituted C 6-14 aryl; wherein the substituents are selected from substituted or unsubstituted C 1～20 alkyl.

3. The symmetrical disulfide compound containing a sulfoxide group according to claim 1, wherein R1 and R2 are the same or different and are each a C1-C4 alkyl group, and R3 and R4 are the same or different and are each a C1-C4 alkyl group. R is selected from the group consisting of substituted or unsubstituted C 1～6 alkyl, substituted or unsubstituted phenyl; wherein the substituents are one or more, independently selected from the group consisting of C 1～6 alkyl, C 1～20 alkyl, C 1～20 alkoxy; the halogen is selected from the group consisting of fluorine, chlorine, bromine, iodine; Ar is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; wherein the substituents are C 1～6 alkyl.

4. The symmetrical disulfide compound containing a sulfoxide group according to claim 1, wherein R is selected from the group consisting of substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted isopropyl; wherein the substituents are one or more, independently selected from the group consisting of methyl, ethyl, octyloxy unsubstituted or substituted with 1 to 20 halogens; preferably the octyloxy substituted with 1 to 20 halogens is Ar is selected from substituted or unsubstituted phenyl, substituted or unsubstituted naphthyl; wherein the substituents are methyl or ethyl; preferably, Ar is phenyl or naphthyl 5. The symmetrical disulfide compound containing a sulfoxide group according to claim 1, wherein The symmetric disulfide compound containing sulfoxide group has any one of the following structural formula I-1 to structural formula I-6:

6. The application of the symmetric disulfide compound containing sulfoxide group according to any one of claims 1-5 as an activating agent in glycosylation reaction. Preferably, the molar ratio of the activating agent to the glycosyl donor is (0.25-0.5):

1.

7. A method of preparing a glycosylated product, characterized by, The method is to use the symmetric disulfide compound containing sulfoxide group according to any one of claims 1-5 as an activating agent, in the presence of trifluoromethanesulfonic anhydride, to activate the glycosyl donor shown in structural general formula (II) and react with the acceptor shown in formula (III), to obtain the glycosylation product shown in formula (IV); The reaction equation is as follows: Gly is a glycosyl group in which one or more hydroxyl groups of a sugar ring are protected by a protecting group; X is a sulfur or selenium atom; R 1 is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group; preferably, R 1 is independently selected from the group consisting of ethyl (Et), isopropyl (i-Pr), cyclohexyl (Cy), 1-adamantyl (Adm), benzyl (Bn), phenyl (Ph), p-methylphenyl (Tol), 2-ethylphenyl (2-EP) or 2,6-dimethylphenyl; and i R is a substituted or unsubstituted alkyl group, a substituted or unsubstituted aryl group; preferably, R o is independently selected from the group consisting of ethyl (Et), isopropyl (i-Pr), cyclohexyl (Cy), 1-adamantyl (Adm), benzyl (Bn), phenyl (Ph), p-methylphenyl (Tol), 2-ethylphenyl (2-EP) or 2,6-dimethylphenyl; and The acceptor shown in formula (III) is selected from saccharides, alcohols, purine nucleophiles containing one or more nucleophilic groups.

8. A method of preparing a glycosylated product, characterized by, The method is to use the symmetric disulfide compound containing sulfoxide group according to any one of claims 1-5 as an activating agent, in the presence of trifluoromethanesulfonic anhydride, to activate the glycosyl donor and react with the acceptor, and the generated glycosylation product can be further activated to initiate continuous glycosylation; The structural general formula of the glycosyl donor is specifically wherein Gly is a sugar group in which one or more hydroxyl groups of the sugar ring are protected with a protecting group; X is a sulfur or selenium atom; R 1 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl; The structural general formula of the acceptor is specifically wherein Gly' is a glycosyl group in which one or more hydroxyl groups of the sugar ring are protected with a protecting group; X' is a sulfur or selenium atom; R 2 is substituted or unsubstituted alkyl, substituted or unsubstituted aryl; Preferably, R 1 、R 2 independently selected from ethyl (Et), isopropyl ( i Pr), cyclohexyl (Cy), 1-adamantyl (Adm), benzyl (Bn), phenyl (Ph), p-methylphenyl (Tol), 2-ethylphenyl ( o EP) or 2,6-dimethylphenyl.

9. The method of claim 7 or 8, wherein, The structural formula of the Gly, Gly' is independently selected from structural general formula (II-a) or structural general formula (II-b): wherein P 1 , P 2 , P 3 , P 4 are each independently selected from the group consisting of hydrogen, alkyl, alkoxy, acyloxy, substituted amino; Preferably, the structural general formula (II-a) has any one of the following structural formula II-01 to structural formula II-16: The structural general formula (II-b) has the following structural formula II-17: The acceptor shown in formula (III) is a glycosyl acceptor containing one or more free hydroxyl groups, having any one of the following structural formula III-01 to structural formula III-11: Alternatively, the acceptor shown in formula (III) is an alcohol acceptor, having any one of the following structural formula III-12 to structural formula III-17: Alternatively, the acceptor shown in formula (III) is a purine acceptor, having the following structural formula III-18: Alternatively, the acceptor shown in formula (III) is a glycosyl acceptor containing a glycoside radical capable of being activated at the anomeric carbon, having any one of the following structural formula III-19 to structural formula III-20: The acceptor shown in formula (III') is a glycosyl acceptor containing a glycoside radical capable of being activated at the anomeric carbon, having any one of the following structural formula III-19 to structural formula III-20:

10. The method of claim 7 or 8, wherein, The molar ratio of the activating agent to trifluoromethanesulfonic anhydride is 1:(1-2), preferably 1:2; The molar ratio of the activating agent to the glycosyl donor shown in structural general formula (II) is 1:(1-6), preferably 1:(1-4); The reaction temperature of the glycosylation reaction is -40℃-30℃; The glycosylation reaction is carried out in an organic solvent, which is one of toluene, dichloromethane, acetonitrile, preferably dichloromethane.

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