Asymmetric disulfide compound containing sulfoxide group as well as preparation method and application of asymmetric disulfide compound

Abstract

The invention belongs to the technical field of chemical synthesis, and discloses an asymmetric disulfide compound containing a sulfoxide group as well as a preparation method and application thereof, and the asymmetric disulfide compound containing the sulfoxide group has a structure as shown in a structural general formula (I). By improving the structure of the compound and the preparation method thereof, the obtained compound as shown in the structural general formula (I) is novel in structure and stable in property; the preparation method has the advantages of cheap and easily available raw materials, simple operation, high reaction yield, convenient separation and purification of intermediates and products, suitableness for industrial production, and high preparation efficiency. Moreover, the compound as shown in the structural general formula (I) can be particularly used as an activating reagent to be applied to glycosylation reaction, is simple and convenient to operate and high in reaction activity when being used for glycosylation reaction, and can be widely applied to activation of thioglycoside and selenoglycoside to construct various substrates such as oxygen glycoside, phenolic glycoside, ester glycoside, nucleoside and carbon glycoside.

Description

TECHNICAL FIELD

[0001] The present application belongs to the technical field of chemical synthesis, and more particularly relates to an asymmetric disulfide compound containing a sulfoxide group, a preparation method and application thereof. BACKGROUND

[0002] Glycosylation reaction refers to a reaction in which a sugar group donor (a sugar group unit with a leaving group introduced by an anomer position derivation) and a sugar group acceptor (a sugar group unit with a nucleophilic site or a non-glycoside unit) are connected by an acetal or ketal bond under the action of an activating agent. The nucleophilic site can be oxygen, nitrogen, carbon, sulfur, etc., and the acetal or ketal bond formed in the reaction process is also called a glycosidic bond.

[0003] Among numerous sugar group donors, thioglycosides and selenoglycosides stand out due to their stability, easy availability, multifunctionality, and convenient control of reaction activity, and are the most commonly used sugar group donors. Mixed anhydride represented by aryl sulfinic acid triflate anhydride (ArSOTf) is a highly efficient thioglycoside / selenoglycoside activating agent, which can effectively activate low-activity donors with equivalent reagents (J. Am. Chem. Soc. 1998, 120, 435-436). However, ArSOTf is unstable and is generally generated in situ by aryl sulfinyl chloride (ArSCl) and silver triflate (AgOTf) for present use. However, most ArSCl is also limited in stability, is easily oxidized, rapidly decomposes upon contact with water, and is not resistant to storage, and has a strong irritating and foul odor. In addition, AgOTf is a noble metal reagent, is sensitive to light, and has strong hygroscopicity. The above shortcomings limit the widespread use of this activation system. Therefore, sugar chemists have been committed to finding substitutes for such sulfinic acid triflate anhydride activating reagents or their precursors.

[0004] Developing stable sulfinyl derivatives to form an activation system with triflic anhydride (Tf2O) is an important direction. So far, various sulfinyl reagents have been developed, such as p-methoxyphenyl benzenesulfinic acid ester 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 benzenesulfinyl morpholine BSM (Synlett 2006, 17, 2846-2850). However, the reaction effect of the above reagents is still inferior to that of the triflic anhydride intermediate (RSOTf). In addition, when the above reagents are applied to the activation of thioglycoside / selenoglycoside donors, an equivalent or even excess amount of the activation reagent is often required. Disulfide compounds can also be used as activation reagents (Org. Lett. 2007, 9, 4647-4650). However, compounds with both sulfinyl and disulfide functional groups have not been used as activation reagents for glycosylation reactions. The applicant's team has reported a compound VII containing sulfoxide, disulfide and sulfide functional groups, which can activate high-activity thioglycoside donors under the action of triflic anhydride Tf2O, but the activation ability is weak and the application is limited. (J. Am. Chem. Soc. 2020, 142, 5498-5503). In addition, reagent VII is also not suitable for the continuous one-pot glycosylation method of adding the activator once and sequentially constructing multiple glycosidic bonds. It can be seen that compound VII is still not an ideal thioglycoside activation reagent.

[0005] SUMMARY

[0006] In view of the above defects or improvement needs of the prior art, the purpose of the present application is to provide an asymmetric disulfide compound containing a sulfoxide group, a preparation method and application thereof. By improving the structure of the compound and the preparation method, an asymmetric disulfide compound containing a sulfoxide group as shown in structural general formula (I) is obtained. The compound has novel structure and stable properties. The preparation method has the advantages of cheap and easily available raw materials, simple operation, high reaction yield, easy separation and purification of intermediates and products, and is suitable for industrial production and efficient preparation. In addition, the compound shown in structural general formula (I) can be used as an activation reagent in glycosylation reactions, and the operation of glycosylation reactions is simple, the reaction activity is high, and it can be widely applied to the activation of thioglycosides and selenoglycosides to construct various oxyglycosides, phenolic glycosides, ester glycosides, nucleosides and carbon glycosides and other substrates.

[0007] To achieve the above-mentioned purpose, according to one aspect of the present application, an asymmetric disulfide compound containing a sulfoxide group is provided, characterized by having a structure as shown in structural general formula (I):

[0008] wherein S is a sulfur atom, and O is an oxygen atom;

[0009] R 1 selected from the group consisting of methyl, ethyl, isopropyl, phenyl, 4-methylphenyl, and

[0010] R 2 selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2,3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, and 4-bromophenyl;

[0011] X is selected from the group consisting of and (CH2)2.

[0012] As a further preferred embodiment of the present application, the structural formula of the asymmetric disulfide compound containing a sulfoxide group is specifically any one of structural formula I-01 to structural formula I-31:

[0013]

[0014]

[0015] According to another aspect of the present application, the present application provides a preparation method of the above-mentioned asymmetric disulfide compound containing a sulfoxide group, characterized in that the preparation method is to use a compound containing a sulfide structure and having a leaving group represented by structural general formula (II) as a starting material,

[0016]

[0017] wherein S is a sulfur atom, and O is an oxygen atom; LG is a leaving group;

[0018] R 1 selected from the group consisting of methyl, ethyl, isopropyl, phenyl, 4-methylphenyl, and

[0019] X is selected from the group consisting of and (CH2)2.

[0020] The preparation method specifically includes the following steps:

[0021] (S1) oxidizing the compound represented by structural general formula (II) with an oxidizing agent to obtain a compound containing a sulfoxide group represented by structural general formula (III);

[0022] (S2) reacting the compound represented by the structural general formula (III) with sodium thiosulfate pentahydrate in an aqueous solution until the reaction is completed, wherein the molar ratio of the compound represented by the structural general formula (III) to sodium thiosulfate pentahydrate is 0.2 to 1.0; and then sequentially adding a hydrophobic solvent, R 2 SH and a base, or sequentially adding a hydrophobic solvent and R 2 SM to prepare an unsymmetrical disulfide compound containing a sulfoxide group represented by the structural general formula (I);

[0023] The reaction scheme is shown as follows:

[0024]

[0025] wherein R 2 M in SM is an alkali metal element;

[0026] R 2 SH and R 2 R 2 is selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2,3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl and 4-bromophenyl.

[0027] As a further preferred embodiment of the present application, in the step (S1), the oxidizing agent is meta-chloroperoxybenzoic acid (m-CPBA) or Eosin Y, or a mixture of hydrogen peroxide (H2O2) and an acid; wherein, when the oxidizing agent is a mixture of hydrogen peroxide (H2O2) and an acid, the acid is any one of acetic acid or diphenyl phosphate;

[0028] In the step (S2), the base is any one of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate or potassium phosphate, and is preferably potassium carbonate;

[0029] The hydrophobic solvent is any one of dichloromethane, dichloroethane, ethyl acetate, toluene or n-butanol, and is preferably dichloromethane;

[0030] The molar ratio of the compound represented by the structural general formula (III) to R 2 SH is 0.2 to 1.0, and the molar ratio of the compound represented by the structural general formula (III) to the base is 0.5 to 1.0; or, the molar ratio of the compound represented by the structural general formula (III) to R 2 SM is 0.2 to 1.0.

[0031] As a further preferred embodiment of the present application, in the structural general formula (II), LG is preferably a bromine atom, a chlorine atom or a p-toluenesulfonyl group;

[0032] M is preferably sodium or potassium.

[0033] According to another aspect of the present application, the present application provides the use of the above asymmetric disulfide compound containing a sulfoxide group as an activating agent in a glycosylation reaction.

[0034] As a further preferred embodiment of the present application, the use is specifically that the asymmetric disulfide compound containing a sulfoxide group participates in the activation of a glycosyl donor to achieve the connection between glycosyl units or the connection between a glycosyl unit and a non-sugar unit.

[0035] As a further preferred embodiment of the present application, the use is specifically that in an organic solvent, a combination of the activating agent as shown in structural formula (I) and triflic anhydride is used as a promoter to make a glycosyl donor as shown in structural formula (IV) undergo a glycosylation reaction with an acceptor as shown in formula (V) to obtain a glycosylation product as shown in formula (VI); the reaction equation is as follows:

[0036]

[0037] In the glycosyl donor as shown in structural formula (IV), Gly is a glycosyl group in which a hydroxyl group and / or an amino group on a sugar ring is protected by a protecting group; Z is a sulfur or selenium atom; R 3 selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl;

[0038] The acceptor as shown in formula (V) is selected from a sugar nucleophile in which a hydroxyl group and / or an amino group on a sugar ring is partially protected by a protecting group, or an alcohol, a phenol, a carboxylic acid, a pyrimidine, a purine, an enol silyl ether nucleophile containing one or more nucleophilic groups.

[0039] As a further preferred embodiment of the present application, in Gly or the acceptor as shown in formula (V), the sugar is independently selected from any one of D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, D-quino sugar, D-fucose, L-fucose, 2-deoxy-L-fucose, D-ribose, 6-deoxy-D-ribose, sialic acid, D-furan glucose, 2-amino-2-deoxy-D-glucose, and 3-aminopolydeoxy sugar.

[0040] In Gly or the acceptor as shown in formula (V), the protecting group is independently selected from any one of acetyl (Ac), benzoyl (Bz), benzyl (Bn), tert-butyldimethylsilyl (TBS), benzaldehyde acetal, carbonate, carbazate, propionyl ketone, benzyloxy carbonyl (Cbz), p-methoxyphenyl (MP), S-2-methylbutyryl (Mba), and p-nitrobenzenesulfonyl (Ns).

[0041] R 3selected from substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted 1-adamantyl, substituted or unsubstituted phenyl; wherein the substituent is one or more, independently selected from methyl, ethyl, methoxy, phenyl;

[0042] The organic solvent is one or more of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, and nitrile solvents;

[0043] The molar ratio of the asymmetric disulfide compound containing a sulfoxide group represented by the structural general formula (I) to the glycosyl donor represented by the structural general formula (IV) is 0.5-1.2;

[0044] The molar ratio of triflic anhydride to the glycosyl donor represented by the structural general formula (IV) is 0.5-1.2;

[0045] The reaction temperature of the glycosylation reaction is in the range of -78-30°C.

[0046] As a further preferred embodiment of the present application, the glycosyl donor represented by the structural general formula (IV) is specifically any one of the compounds represented by the structural formula IV-01 to the structural formula IV-29:

[0047]

[0048] The acceptor represented by the formula (V) is a sugar nucleophile with a hydroxyl and / or amino group on the sugar ring being partially protected by a protecting group, and is specifically any one of the compounds represented by the structural formula V-01 to the structural formula V-13:

[0049]

[0050] Alternatively, the acceptor represented by the formula (V) is an alcohol nucleophile, and is specifically any one of the compounds represented by the structural formula V-14 to the structural formula V-18:

[0051]

[0052] Alternatively, the acceptor represented by the formula (V) is a phenol or carboxylic acid nucleophile, and is specifically the compound represented by the structural formula V-19 or the structural formula V-20:

[0053]

[0054] Alternatively, the acceptor represented by the formula (V) is a pyrimidine or purine nucleophile, and is specifically any one of the compounds represented by the structural formula V-21 to the structural formula V-24:

[0055]

[0056] Alternatively, the acceptor represented by the formula (V) is an enol silyl ether nucleophile, and is specifically the compound represented by the structural formula V-25:

[0057]

[0058] By the above technical scheme conceived by the present application, compared with the prior art, the present application first reports the asymmetric disulfide compound containing a sulfoxide group with the structure shown in structural general formula (I), and no open literature reports the compound shown in structural general formula (I), the corresponding preparation method, and the application as an activating agent in glycosylation reaction. Specifically, the present application can achieve the following beneficial effects:

[0059] 1) The compound shown in structural general formula (I) of the present application has novel structure, stable properties, easy storage (can be stored stably at room temperature in air atmosphere, and no obvious decrease in reaction activity) and no irritating odor;

[0060] 2) The preparation method of the asymmetric disulfide compound containing a sulfoxide group of the present application has the advantages of cheap and easily available raw materials, simple operation, high reaction yield, easy separation and purification of intermediates and products, and is suitable for industrial production. The preparation method can use the compound containing a sulfide structure and having a leaving group shown in structural general formula (II) as a starting material, and the target asymmetric disulfide compound containing a sulfoxide group is obtained through two stages of sulfide oxidation and asymmetric disulfide bond construction (specifically including one-step oxidation reaction and two-step disulfide construction reaction). The reaction route is shown as follows:

[0061]

[0062] The preparation method has the following advantages: i) simple operation, not sensitive to water and oxygen; ii) the reagents and solvents used are cheap, easily available, low in toxicity, low in cost and environmentally friendly; iii) high synthesis efficiency, the total yield of most examples is more than 70%, and the highest can reach 87%; iv) convenient purification, for example, the intermediates shown in structural general formula (II) are all solid, which can be recrystallized and purified by beating; after the addition of sodium thiosulfate pentahydrate to introduce water-soluble sodium thiosulfinate functional group, it can be extracted and purified; the final product shown in structural general formula (I) can be recrystallized and purified by beating, and column chromatography purification is also easy due to the large difference in polarity between the main product and the by-product (symmetric disulfide); v) the preparation scale can be enlarged, and it is suitable for industrial scale production; for example, compound I-02 has been prepared on a scale of hundreds of grams (as shown in Example 41 hereinafter), and the synthesis scale of compound I-09 reaches the order of 25 grams (as shown in Example 10 hereinafter).

[0063] In the preparation process, the molar ratio of the compound of structural formula (III) to sodium thiosulfate pentahydrate is controlled to be 0.2-1.0, and they are reacted until the conversion is complete. On the one hand, it can ensure that the conversion of structural formula (III) is complete to avoid interfering with the subsequent separation of structural formula (I) (because the polarity difference between structural formula III and structural formula I is not large), on the other hand, it can also reduce the generation of by-products. In addition, the compound of structural formula (III) is mostly solid, and when the synthesis scale is large, recrystallization operation can be adopted, and because the polarity difference between the main and by-product in the disulfide bond construction stage is large, the intermediates and product compound of formula (I) are very easy to separate and purify.

[0064] 3) And in the disulfide construction reaction, the order of adding the reactants to the reaction system needs to be strictly followed, that is, adding the hydrophobic solvent, R 2 SH and base in turn, or adding the hydrophobic solvent and R 2 SM in turn, because the hydrophobic solvent can protect the compound of structural formula (I) generated in the system from being decomposed by the base and reduce the generation of by-products; in addition, the operation of "adding R 2 SH first and then adding base" is to control the acid-base degree in the reaction system and to protect the compound of structural formula (I) generated in the system.

[0065] 4) The unsymmetrical disulfide compound containing a sulfoxide group obtained by the present application can be used as an activating agent in glycosylation reaction. The unsymmetrical disulfide compound containing a sulfoxide group obtained by the present application contains disulfide and sulfoxide functional groups, and can generate a highly active thiophilic intermediate in situ under the action of triflic anhydride, thereby achieving an effect similar to that of a triflic anhydride active intermediate of a sulphenic acid, and avoiding the use of toxic, malodorous, expensive, unstable or metal-containing reagents commonly used in the preparation of the active intermediate. The amount of the reagent and the anhydride can be as low as 0.5 equivalent of the glycosyl donor (i.e., the molar ratio of the activating agent to the glycosyl donor is 0.5:1, and the molar ratio of triflic anhydride to the glycosyl donor is 0.5:1).

[0066] 5) The unsymmetrical disulfide compound containing a sulfoxide group obtained by the present application has a wide range of applications in glycosylation reaction, and can be used to construct carbon-oxygen, carbon-nitrogen and carbon-carbon glycosidic bonds, and can achieve efficient synthesis of oxyglycosides, phenolic glycosides, ester glycosides, nucleosides and nitrogen glycosides. The operation is simple, the reaction time is short (the fastest can be completed within 5 minutes), and has good application prospect.

[0067] In addition, the present application is also suitable for activating some low-activity glycosyl donors (such as disarmed glycosyl donors, etc., as exemplified in Example 42 below), which is not possessed by other activating agents in the prior art (as exemplified in Comparative Example 1 below). DETAILED DESCRIPTION

[0068] In order to make the objectives, technical solutions and advantages of the present application clearer, the present application will be further described in details below in combination with embodiments. It should be understood that the specific embodiments described herein are only used to explain the present application and should not be used to 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.

[0069] The asymmetric disulfide compounds containing sulfoxide groups as shown in structural general formula (I) in the present application can be synthesized according to embodiments 1-41, and their effects as activating agents in glycosylation reactions can be seen in embodiments 42-72 below. The following are specific embodiments:

[0070] Table 1 shows examples of compounds satisfying structural general formula (I) of the present application

[0071]

[0072]

[0073]

[0074] The asymmetric disulfide compounds containing sulfoxide groups as shown in structural general formula (I) in the present application can be prepared according to the following methods:

[0075]

[0076] The preparation method includes two stages of thioether oxidation and asymmetric disulfide bond construction, i.e. using a compound containing a thioether structure and having a leaving group as shown in structural general formula (II) as a starting material, introducing a sulfoxide functional group by oxidation with an oxidizing agent to obtain compound (III); in an aqueous solution, the compound as shown in structural general formula (III) is reacted with sodium thiosulfate pentahydrate until the conversion is complete; then, a hydrophobic solvent, R 2 SH, a base or a hydrophobic solvent and R 2 SM are sequentially added to obtain the compound as shown in structural general formula (I).

[0077] Among them, the operation steps of the selective oxidation stage are different depending on the oxidizing agent, and are as follows:

[0078] Oxidation Step A: Compound (II) was weighed into a reaction flask, dissolved in dichloromethane (to make the concentration of compound of structural formula II c = 0.2 M), a solution of m-chloroperbenzoic acid (m-CPBA, 1.0 equivalent) in dichloromethane was slowly added dropwise into the above reaction flask at -20°C, after the dropwise addition was completed, the reaction was continued at -20°C for 0.5 hours until the reaction was complete, saturated aqueous sodium thiosulfate solution was added to terminate the reaction, the reaction system was diluted with ethyl acetate, washed successively with water, saturated sodium bicarbonate, saturated sodium chloride solution, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated, and compound (III) was separated by column chromatography or recrystallization.

[0079] Oxidation Step B: Compound (II) and Eosin Y (0.05 equivalent) were weighed into a reaction flask, dissolved in ethanol (to make the concentration of compound of structural formula II c = 0.2 M), and then irradiated with a 5W Blue LED lamp for a certain period of time until the starting material was completely reacted, the reaction system was diluted with ethyl acetate, washed successively with water and saturated sodium chloride solution, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated, and compound (III) was separated by column chromatography.

[0080] Oxidation Step C: Compound (II) and diphenyl phosphate ((PhO)2P(O)OH, 0.1 equivalent) were weighed into a reaction flask, dissolved in ethyl acetate, and then 30wt% hydrogen peroxide aqueous solution was added under ice bath, the reaction system was warmed to 60°C for a certain period of time until the reaction was complete, saturated aqueous sodium thiosulfate solution was added to terminate the reaction, the reaction system was diluted with ethyl acetate, washed successively with water, saturated sodium bicarbonate and saturated sodium chloride solution, the organic phases were combined, dried over anhydrous sodium sulfate, filtered and concentrated, and compound (III) was purified by column chromatography or recrystallization.

[0081] Oxidation Step D: Compound (II) was weighed into a reaction flask, acetic acid (1.0 equivalent) was added, and 30wt% hydrogen peroxide aqueous solution (4.0 equivalent) was slowly added dropwise at room temperature, the reaction was maintained at room temperature until the reaction was complete (as the reaction proceeded, the product gradually precipitated out). After sufficient stirring with the addition of sufficient water in the reaction system, filtration under reduced pressure and lyophilization, compound (III) was obtained.

[0082] Example 1: Selective oxidation of different types of oxidants to introduce sulfoxide functional group (taking the synthesis of compound III-03 as an example)

[0083]

[0084]

[0085] Following the synthesis of II-03 according to the literature (Tetrahedron Lett., 2017, 58, 2381-2384), reference General Oxidation Procedure A was made with 2-(2-propylthio)benzyl chloride II-03 as the starting material to obtain white solid III-03 (5.0 g, 94%) by recrystallization operation; reference General Oxidation Procedure B was made with 2-(2-propylthio)benzyl chloride II-03 as the starting material to obtain white solid III-03 (100 mg, 94%); reference General Oxidation Procedure C was made with 2-(2-propylthio)benzyl chloride II-03 as the starting material to obtain white solid III-03 (46 g, 91%) by recrystallization operation. 1 H NMR (600 MHz, CDC13) δ 7.86 (1H, d, J = 7.2 Hz, Ar-H), 7.54-7.46 (3H, m, Ar-H), 4.71 (2H, s, -CH2Ph), 3.05-2.99 (1H, m, -CH(C H (CH3)2), 1.31 (3H, d, J = 6.6 Hz, -CH(C H 3)2), 1.17 (3H, d, J = 6.6 Hz, -CH(C H 3)2). 13 C NMR (100 MHz, CDC13) δ 141.7, 135.6, 131.6, 131.1, 129.7, 126.0, 54.3, 41.6, 17.6, 13.3. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 10 H 13 ClOSNa 239.0268; Found 239.0265. Different types of oxidants have little effect on the yield, and General Oxidation Procedure A and General Oxidation Procedure C are particularly suitable for large-scale synthesis of target products.

[0086] Example 2: Selective oxidation by hydrogen peroxide-acid mixture to introduce sulfoxide function (as an example of the synthesis of compound III-01)

[0087]

[0088]

[0089] After synthesis of II-01 according to the literature (J. Org. Chem., 2011, 76, 1513-1520), reference was made to the general oxidation procedure C, with 2- methylthiobenzyl chloride II-01 as starting material, to obtain white solid III-01 (14 g, 94%) by recrystallization procedure; reference was made to the general oxidation procedure D, with 2-methylthiobenzyl chloride II-01 as starting material, to obtain white solid III-01 (5 g, 91%). 1 HNMR (600 MHz, CDC13) δ 8.03 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.58 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.48 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.40 (1H, dd, J = 7.2, 1.2 Hz, Ar-H), 4.80 (1H, d, J = 11.4 Hz, -CH2Ph), 4.61 (1H, d, J = 11.4 Hz, -CH2Ph), 2.81 (3H, s, -CH3). 13 CNMR (150 MHz, CDC13) δ 145.5, 134.3, 131.7, 130.8, 130.7, 124.4, 44.2, 41.8. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C8H9ClOSNa 210.9955; Found 210.9949.

[0090] Example 3: Synthesis of compound III-02

[0091]

[0092] After synthesis of II-02 according to the similar method of synthesis of compound 5c in the literature (J. Org. Chem., 2011, 76, 1513-1520), reference was made to the general oxidation procedure C, with 2-ethylthiobenzyl chloride II-02 as starting material, to obtain white solid III-02 (879 mg, 92%) by recrystallization procedure. 1 H NMR (600 MHz, CDC13) δ 8.03 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.58 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.48 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.40 (1H, dd, J = 7.2, 1.2 Hz, Ar-H), 4.80 (1H, d, J = 11.4 Hz, -CH2Ph), 4.61 (1H, d, J = 11.4 Hz, -CH2Ph), 2.81 (3H, s, -CH3). H2 CH3), 2.88-2.82 (1H, m, -C H 2 CH3), 1.29 (3H, t, J = 7.8 Hz, -CH2CH3), 1.27 (3H, t, J = 7.8 Hz, -CH2CH3). H 3). 13 C NMR (150 MHz, CDC13) δ 143.1, 134.9, 131.6, 131.0, 130.2, 125.4, 50.6, 41.7, 6.9. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C9H 11 ClOSNa 225.0111; Found 225.0106.

[0093] Example 4: Synthesis of compound III-04

[0094]

[0095] After synthesis of II-04 according to literature (Monatsh. Chem., 1965, 96, 182-207), reference to General oxidation procedure A was made to yield III-04 (0.4 g, 95%) as a white solid, using 2-phenylthiobenzyl chloride II-04 as starting material. 1 H NMR (600 MHz, CDC13) δ 7.84 (1H, m, Ar-H), 7.65-7.64 (2H, m, Ar-H), 7.50-7.48 (1H, m, Ar-H), 7.47-7.43 (5H, m, Ar-H), 4.88 (1H, d, J = 12.0 Hz, -CH2Ph), 4.70 (1H, d, J = 12.0 Hz, -CH2Ph). 13 C NMR (150 MHz, CDC13) δ 144.6, 144.3, 136.1, 132.0, 131.3, 130.9, 130.3, 129.6, 126.5, 125.6, 41.8. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 13 H 11 ClOSNa 273.0111; Found 273.0111.

[0096] Example 5: Synthesis of compound III-05

[0097]

[0098] After synthesis of II-05 according to the literature (Collect. Czech. Chem. Commun., 1968, 33, 1895-1910), reference to the general oxidation procedure A, 2-(4-methylphenylsulfanyl)benzyl chloride II-05 was used as the starting material to give III-05 as a white solid (0.4 g, 97%). 1 H NMR (400 MHz, CDC13) δ 7.90-7.86 (1H, m, Ar-H), 7.54-7.44 (5H, m, Ar-H), 7.25 (2H, d, J = 6.8 Hz, Ar-H), 4.83 (1H, d, J = 12.0 Hz, -CH2Ph), 4.67 (1H, d, J = 12.0 Hz, -CH2Ph), 2.35 (s, 3H, -CH3). 13 C NMR (150 MHz, CDC13) δ 144.4, 142.0, 141.4, 135.8, 131.9, 130.8, 130.3, 126.2, 125.8, 41.9, 21.6. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 14 H 13 ClOSNa 287.0268; Found 287.0261.

[0099] Example 6: Synthesis of compound III-06

[0100]

[0101] After synthesis of S1 according to the literature (J. Am. Chem. Soc. 2020, 142, 5498-5503), S1 (34 mg, 0.16 mmol), 4-dimethylaminopyridine (4 mg, 0.03 mmol) were weighed into a reaction vial, dissolved in dichloromethane (0.8 mL), and then triethylamine (45 μL, 0.32 mmol), p-toluenesulfonyl chloride (62 mg, 0.32 mmol) were added successively under ice bath. After the addition was completed, it was moved to room temperature and reacted for 24 hours. After the reaction was completed, the reaction system was diluted with ethyl acetate, and then washed successively with water, saturated sodium bicarbonate, and saturated sodium chloride solution. Subsequently, the organic phase was dried over anhydrous sodium sulfate, filtered and concentrated, and the crude product was purified by silica gel column chromatography to give II-06 as an oily liquid (29 mg, 78%). 1H 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). 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 12 H 17 OClSNa 267.0581; Found 267.0582.

[0102] Following the general oxidation procedure A, 2-(2-propylthio)-6- ethylbenzyl chloride II-06 was used as starting material to give III-06 as a colorless liquid (30 mg, 92%). 1 H NMR (400 MHz, CDC13) δ 7.72 (1H, d, J = 8.0 Hz, Ar-H), 7.49 (1H, t, J = 8.0 Hz, Ar-H), 7.37 (1H, d, J = 7.6 Hz, Ar-H), 4.80 (1H, d, J = 12.0 Hz, -CH2Ph), 4.76 (1H, d, J = 12.0 Hz, -CH2Ph), 3.08 (1H, hept, J = 6.8 Hz, -C H (CH3)2), 2.82 (2H, q, J = 7.6 Hz, -C H 2CH3), 1.35 (3H, d, J = 7.2 Hz, -CH(C H 3)2), 1.29 (3H, t, J = 7.6 Hz, -CH2C H 3), 1.14 (3H, d, J = 6.4 Hz, -CH(C H 3)2). 13C NMR (150 MHz, CDC13) δ 145.1, 142.7, 132.7, 131.8, 129.9, 123.8, 54.0, 38.3, 25.0, 18.0, 15.4, 13.0. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + calcd for C 12 H 17 ClOSNa 267.0581; Found 267.0584.

[0103] Example 7: Synthesis of compound III-07

[0104]

[0105] Compound II-07 (170 mg, 3% for 4 steps) was synthesized according to the similar procedure of synthesis of compound XXXV in literature (Monatsh. Chem. 1965, 96, 182-207) using commercially available material S2 as starting material. Rf = 0.53 (petroleum ether). f = 0.53 (petroleum ether). 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 C NMR (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 + Calcd for C 17 H 13 ClOSNa 323.0268; Found 323.0274.

[0106] Referring to the general oxidation procedure A, using 2-phenylsulfanyl-3- chloromethylnaphthalene II-07 as starting material, gave III-07 (136 mg, 77%). 1H NMR (400 MHz, CDC13) δ 8.49 (1H, s, Ar-H), 7.97 (1H, m, Ar-H), 7.93 (1H, s, Ar-H), 7.87-7.85 (1H, m, Ar-H), 7.68-7.65 (2H, m, Ar-H), 7.61-7.56 (2H, m, Ar-H), 7.44 (3H, m, Ar-H), 4.82 (1H, d, J = 12.4 Hz, -CH2), 4.71 (1H, d, J = 12.0 Hz, -CH2). 13 C NMR (150 MHz, CDC13) δ 144.5, 141.0, 134.5, 133.0, 131.9, 131.7, 130.8, 129.7, 128.9, 128.7, 128.1, 128.0, 127.6, 126.5, 42.5. HRMS (ESI-TOF) m / z: [M + Na] + calcd for C 17 H 13 ClOSNa 323.0268; found 323.0277.

[0107] Example 8: Synthesis of compound III-08

[0108]

[0109] After synthesizing S3 according to the literature (Chem. Sci., 2022, 13, 8759- 8765), S3 (150 mg, 0.16 mmol) was weighed into a reaction bottle, dissolved in dichloromethane (0.4 mL), and a dichloromethane solution of sulfonyl chloride (18 μL, 0.25 mmol) was slowly added dropwise under ice bath. After the addition was completed, it was removed to room temperature and reacted for 0.5 hours. After the reaction was completed, the reaction system was diluted with ethyl acetate, and then washed with water, saturated sodium bicarbonate, and saturated sodium chloride solution. Subsequently, 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 compound II-08 (98 mg, 64%). H NMR (600 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), 2.29-2.27 (3H, m, -CH2), 2.22-2.20 (3H, m, -CH2). H 2C H 2C6F 13 ). 13C NMR (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] + Calcd for C 26 H 19 ClF 26 O2SNa 947.0271; Found 947.0276.

[0110] Reference to the general oxidation procedure A, afforded III-08 as a colorless liquid (100 mg, 85%). 1 H NMR (600 MHz, CDC13) δ 7.90-7.89 (1H, m, Ar-H), 7.55-7.49 (3H, m, Ar-H), 4.76 (1H, d, J = 12.0 Hz, -CH2Ph), 4.67 (1H, d, J = 12.0 Hz, -CH2Ph), 3.79-3.68 (6H, m), 3.64-3.57 (2H, m), 3.31-3.27 (1H, m), 2.39-2.30 (2H, m), 2.26-2.19 (2H, m). 13 C NMR (150 MHz, CDC13) δ 141.1, 135.8, 131.9, 131.3, 129.8, 125.7, 66.8, 64.3, 63.9, 63.5, 63.2, 41.2, 31.5 (t, J = 21.5 Hz, -CH2 C H2C6F 13 ), 31.4 (t, J = 21.6 Hz, -CH2 C H2C6F 13 ). HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 26 H 19 ClF 26 O3SNa 963.0220; Found 963.0209.

[0111] Example 9: Synthesis of compound III-09

[0112]

[0113] Following a similar procedure to that described in the literature (Synthesis., 2011, 3, 397-408) for the synthesis of compound 10, II-09 was synthesized as a colorless liquid (40 mg, 85%) from 3-chloropropyl phenyl sulfide II-09, referring to the general oxidation procedure A. The obtained product was immediately tested by NMR, and the results are as follows: 1 H NMR (600 MHz, CD2Cl2) δ 7.74-7.73 (2H, m, Ar-H), 7.56-7.51 (5H, m, Ar-H), 7.37-7.35 (2H, d, J = 8.0 Hz, Ar-H), 4.12-4.08 (1H, m), 4.07-4.03 (1H, m), 2.88-2.84 (1H, m), 2.70-2.66 (1H, m), 2.44 (3H, s, -CH3), 2.13-2.06 (1H, m), 1.91-1.84 (1H, m). 13 C NMR (150 MHz, CD2Cl2) δ 145.6, 144.0, 133.0, 131.3, 130.3, 129.6, 128.2, 124.2, 69.4, 52.9, 22.0, 21.7. HRMS (ESI-TOF) m / z: [M+H] + Calcd for C 16 H 19 O4S2 339.0719; Found 339.0715.

[0114] The specific optimization data of the type of hydrophobic solvent and base in the asymmetric disulfide construction stage of the compound represented by formula (I) in the present application are shown in Examples 10-11:

[0115] Example 10: Screening of the type of hydrophobic solvent (taking the synthesis of compound I-09 as an example)

[0116]

[0117]

[0118] The specific operation is as follows: weigh compound III-03 and sodium thiosulfate pentahydrate into a reaction bottle, add an appropriate amount of water (the concentration of sodium thiosulfate pentahydrate is c = 0.4 M), and heat to 50°C for 4 hours. After the reaction system is clear and TLC monitoring shows that compound III-03 is completely converted, without any post-treatment operation, cool the above reaction system to 0°C, and add hydrophobic solvent (v 憎水溶剂 / v 体系中水=1:6, volume ratio, the same below), and an aqueous solution of sodium thiophenolate (1.2 equivalents, concentration c = 1 M) were reacted at 0°C for 6 hours, diluted with dichloromethane, washed three times with water, and the combined organic phases dried over anhydrous sodium sulfate, filtered, concentrated, and purified by column chromatography to yield I-09 as a colorless oily liquid. Different hydrophobic solvents exhibited varying reaction efficiencies, with dichloromethane providing the best results (1.34 g, 90% for two steps; scaled-up reaction conditions using these conditions yielded 25 g of I-09 with a yield of 84% over two steps, a slightly lower yield). 1 H NMR(400MHz,CDCl3)δ7.83-7.80(1H,dd,J=8.0,2.0Hz,Ar-H),7.46-7.42(3H,m,Ar-H),7.37(1H,td,J=7.2,1.2Hz,Ar-H),7.33-7 .27(3H,m,Ar-H),7.21(1H,m,Ar-H),4.09(1H,d,J=12.8Hz,-CH2Ph),4.03(1H,d,J=12.8Hz,-CH2Ph),2.91(1H,hept,J=7.2Hz,-C H (CH3)2),1.22(3H,d,J=7.2Hz,-CH3),1.10(3H,d,J=7.2Hz,-CH3). 13 C NMR (100MHz, CDCl3) δ141.6,136.6,134.5,131.4,131.1,129.3,128.8,128.6,127.6,125.9,54.2,39.2,17.6,13.2.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 16 H 18 OS3Na 345.0412; Found 345.0411. Note: In the following examples, dichloromethane was used as the hydrophobic solvent unless otherwise specified.

[0119] Example 11: Screening of base types (taking the synthesis of compound I-02 as an example)

[0120]

[0121]

[0122] The specific operation is as follows: weigh compound III-01, sodium thiosulfate pentahydrate into a reaction bottle, add an appropriate amount of water (the concentration c of sodium thiosulfate pentahydrate is 0.4 M), heat to 50°C, and react for 4 hours. After the reaction system is clear and TLC monitoring shows that compound III-01 is completely converted, without any post-treatment operation, cool the above reaction system to 0°C, and sequentially add hydrophobic solvent dichloromethane (v 二氯甲烷 / v 体系中水 = 1:6), 4-methyl thiophenol (1.2 equivalents), and an aqueous base (1.0 equivalent, concentration c = 0.8 M) and react for 2.5 hours. After dilution with dichloromethane, washing with water three times, drying with anhydrous sodium sulfate, filtration and concentration, purification by recrystallization operation, white solid I-02 is obtained. When potassium carbonate is used as the base, the reaction effect is best (1.5 g, 92% for 2 steps). 1 H NMR (600 MHz, CDCl3) δ 7.98 (1H, dd, J = 7.8, 0.6 Hz, Ar-H), 7.51 (1H, td, J = 7.8, 0.6 Hz, Ar-H), 7.41 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.30 (2H, d, J = 8.4 Hz, Ar-H), 7.26 (1H, d, J = 7.8 Hz, Ar-H), 7.09 (2H, d, J = 8.4 Hz, Ar-H), 4.13 (1H, d, J = 13.2 Hz, -CH2Ph), 4.00 (1H, d, J = 13.2 Hz, -CH2Ph), 2.68 (3H, s, -CH3), 2.32 (3H, s, -CH3). 13 C NMR (150 MHz, CDCl3) δ 145.3, 138.3, 133.9, 133.0, 131.4, 131.2, 130.1, 129.9, 129.7, 124.4, 44.0, 39.1, 21.3. HRMS (ESI-TOF) m / z: [M+Na] + Calcd for C 15 H 16 OS3Na 331.0255; Found 331.0257. Note: In subsequent examples, unless otherwise specified, potassium carbonate is selected as the base.

[0123] Examples 12-40: Asymmetric disulfide construction stage of compounds represented by structural general formula (I) of the present application

[0124] Unless otherwise specified, the asymmetric disulfide construction stage of examples 12-40 can be carried out according to the following two sets of standard operation procedures:

[0125] Dithioether construction step D: Compound (III), sodium thiosulfate pentahydrate (1.3 eq.) were weighed into a reaction flask, and an appropriate amount of water was added (to give a concentration c = 0.4 M of sodium thiosulfate pentahydrate). Compound (III) was observed to be suspended in water. After the reaction system was heated to 50 °C for a period of time, the reaction system was clear and free of insoluble matter. After TLC monitoring of the complete conversion of compound (III), the above reaction system was cooled to 0 °C without any post-treatment operation. Dichloromethane (v 二氯甲烷 / v 体系中水 = 1:6), an aqueous solution of R 2 SH (1.2 eq.) and potassium carbonate (1.0 eq., concentration c = 0.8 M of potassium carbonate) were sequentially added. After the reaction was carried out for a certain period of time, it was diluted with dichloromethane, washed with water three times, and the organic phase was combined and dried over anhydrous sodium sulfate. After filtration and concentration, the asymmetric dithioether compound (I) containing a sulfoxide group was purified by column chromatography or recrystallization. 2 SM (1.2 eq.) (concentration c = 1 M of SM) was added. After the reaction was carried out for a certain period of time, it was diluted with dichloromethane, washed with water three times, and the organic phase was combined and dried over anhydrous sodium sulfate. After filtration and concentration, the asymmetric dithioether compound (I) containing a sulfoxide group was purified by column chromatography or recrystallization.

[0126] Dithioether construction step E: Compound (III), sodium thiosulfate pentahydrate (1.3 eq.) were weighed into a reaction flask, and an appropriate amount of water was added (to give a concentration c = 0.4 M of sodium thiosulfate pentahydrate). Compound (III) was observed to be suspended in water. After the reaction system was heated to 50 °C for a period of time, the reaction system was clear and free of insoluble matter. After TLC monitoring of the complete conversion of compound (III), the above reaction system was cooled to 0 °C without any post-treatment operation. Dichloromethane (v 二氯甲烷 / v 体系中水 = 1:6), an aqueous solution of R 2 SH (1.2 eq.) and potassium carbonate (1.0 eq., concentration c = 0.8 M of potassium carbonate) were sequentially added. After the reaction was carried out for a certain period of time, it was diluted with dichloromethane, washed with water three times, and the organic phase was combined and dried over anhydrous sodium sulfate. After filtration and concentration, the asymmetric dithioether compound (I) containing a sulfoxide group was purified by column chromatography or recrystallization.

[0127] Example 12: Synthesis of compound I-01

[0128] Referring to the general dithioether construction step D, compound III-01 was used as the starting material (wherein R 2 SM is sodium thiophenol), and white solid I-01 (1.4 g, 90% for 2 steps) was obtained. 1H NMR (400 MHz, CDC13) δ 7.97 (1H, dd, J = 8.0, 1.2 Hz, Ar-H), 7.50 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.42-7.38 (3H, m, Ar-H), 7.30-7.20 (4H, m, Ar-H), 4.14 (1H, d, J = 12.8 Hz, -CH2Ph), 4.00 (1H, d, J = 12.8 Hz, -CH2Ph), 2.69 (1H, s, -CH3). 13 C NMR (150 MHz, CDC13) δ 145.2, 136.5, 133.8, 131.4, 131.3, 129.7, 129.3, 129.0, 127.8, 124.4, 44.0, 39.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 14 H 14 OS3Na 317.0099; Found 317.0100.

[0129] Example 13: Synthesis of compound I-03

[0130] Referring to the general disulfide construction procedure Step E, compound III-01 was used as the starting material (wherein R 2 SH is 4-methoxythiophenol) to give colorless oily liquid I-03 (1.6 g, 93% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.97 (1H, dd, J = 8.0, 1.2 Hz, Ar-H), 7.50 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.42-7.38 (3H, m, Ar-H), 7.30-7.20 (4H, m, Ar-H), 4.14 (1H, d, J = 12.8 Hz, -CH2Ph), 4.00 (1H, d, J = 12.8 Hz, -CH2Ph), 2.69 (1H, s, -CH3). 13 C NMR (150 MHz, CDC13) δ 145.2, 136.5, 133.8, 131.4, 131.3, 129.7, 129.3, 129.0, 127.8, 124.4, 44.0, 39.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 15 H16 O2S3Na347.0205; Found 347.0207.

[0131] Example 14: Synthesis of Compound I-04

[0132] Referring to the general disulfide construction step E, compound III-01 is used as the starting material (where R 2 SH is 4-bromobenzenethiol) to give a white solid Ⅰ-04 (200 mg, 58% for 2 steps). 1 H NMR (600MHz, CDCl3) δ7.98 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.51 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.40-7.38 (3H, m, Ar- H),7.27-7.23(3H,m,Ar-H),4.12(1H,d,J=13.2Hz,-CH2Ph),4.00(1H,d,J=13.2Hz,-CH2Ph),2.72(3H,s,-CH3). 13 C NMR(150MHz, CDCl3)δ145.3,135.8,133.7,132.3,131.3,130.2,129.8,124.5,121.7,44.0,39.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 14 H 13 BrOS3Na 394.9204; Found394.9207.

[0133] Example 15: Synthesis of Compound I-05

[0134] Referring to the general disulfide construction step E, compound III-01 is used as the starting material (where R 2 SH is 4-nitrothiophenol) to give a light yellow solid Ⅰ-05 (150 mg, 49% for 2 steps). 1 H NMR (400MHz, CDCl3) δ8.13-8.07(2H,m,Ar-H),7.97(1H,d,J=7.2Hz,Ar-H),7.54-7.45(3H,m,Ar-H),7.36(1H,td,J=7.6,1. 2Hz, Ar-H), 7.23 (1H, d, J = 7.6 Hz, Ar-H), 4.15 (1H, d, J = 12.8 Hz, -CH2Ph), 4.05 (1H, d, J = 13.2 Hz, -CH2Ph), 2.78 (3H, s, -CH3). 13C NMR(100MHz, CDCl3)δ146.6,145.8,145.2,133.4,131.5,131.3,130.1,126.5,124.6,124.3,43.9,39.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcdfor C 14 H 13 NO3S3Na 361.9950; Found 361.9949.

[0135] Example 16: Synthesis of Compound I-06

[0136] Referring to the general disulfide construction step D, compound III-01 was used as the starting material (where R 2 SM is sodium thiomethoxide) to give a colorless oily liquid Ⅰ-06 (400 mg, 75% for 2 steps). 1 H NMR (400MHz, CDCl3) δ8.02(1H,dd,J=8.0,1.2Hz,Ar-H),7.54(1H,td,J=7.8,1.2Hz,Ar-H),7.45(1H,td,J=7.8,1.2Hz,Ar-H),7.35( 1H,dd,J=7.8,0.8Hz,Ar-H),4.11(1H,d,J=13.2Hz,-CH2Ph),3.96(1H,d,J=12.8Hz,-CH2Ph),2.82(3H,s,-CH3),2.17(3H,s,-CH3). 13 C NMR(100MHz, CDCl3)δ145.2,134.7,131.3,131.1,129.6,124.4,44.1,38.5,23.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcdfor C9H 12 OS3Na 254.9942; Found 254.9941.

[0137] Example 17: Synthesis of Compound I-07

[0138] Referring to the general disulfide construction step D, compound III-02 is used as the starting material (wherein R 2 SM is sodium thiophenolate), and a light yellow oily liquid Ⅰ-07 (690 mg, 91% for 2 steps) was obtained. 1H NMR (400 MHz, CDC13) δ 7.89 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.47 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.40 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.39-7.33 (2H, m, Ar-H), 7.29 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 6.83-6.79 (m, 2H, Ar-H), 4.09 (1H, d, J = 12.6 Hz, -CH2Ph), 4.03 (1H, d, J = 12.6 Hz, -CH2Ph), 3.79 (3H, s, -OMe), 2.90-2.77 (1H, m, -CH2), 2.75-2.64 (1H, m, -CH2), 1.19 (3H, t, J = 7.2 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 143.0, 136.5, 134.1, 131.5, 131.2, 129.3, 129.2, 128.8, 127.7, 125.3, 50.5, 39.1, 7.0. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 15 H 16 OS3Na 331.0255; Found 331.0254.

[0139] Example 18: Synthesis of compound I-08

[0140] Referring to the general disulfide construction procedure Step E, compound III-02 was used as the starting material (wherein R 2 SH is 4-methoxythiophenol) to give colorless oily liquid I-08 (1.5 g, 90% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.89 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.47 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.40 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.39-7.33 (2H, m, Ar-H), 7.29 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 6.83-6.79 (m, 2H, Ar-H), 4.09 (1H, d, J = 12.6 Hz, -CH2Ph), 4.03 (1H, d, J = 12.6 Hz, -CH2Ph), 3.79 (3H, s, -OMe), 2.90-2.77 (1H, m, -CH2), 2.75-2.64 (1H, m, -CH2), 1.19 (3H, t, J = 7.2 Hz, -CH3). 13CNMR160.2,143.0,134.2,133.0,131.5,131.1,129.1,127.4,125.3,114.9,55.7,50.4,39.1,7.0.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 16 H 18 O2S3Na 361.0361; Found 361.0362.

[0141] Example 19: Synthesis of Compound I-10

[0142] Referring to the general disulfide construction step E, compound III-03 is used as the starting material (wherein R 2 SH is 4-methylthiophenol) to obtain a light yellow oily liquid Ⅰ-10 (1.43 g, 92% for 2 steps). 1 H NMR(600MHz,CD2Cl2)δ7.79(1H,d,J=7.8Hz,Ar-H),7.47(1H,t,J=7.8Hz,Ar-H),7.41(1H,t,J=7.8Hz,Ar-H),7.36(3H,d,J=7.8Hz ,Ar-H),7.14(2H,d,J=7.8Hz,Ar-H),4.13(1H,d,J=12.6Hz,-CH2Ph),4.03(1H,d,J=12.6Hz,-CH2Ph),2.87(1H,hept,J=6.6Hz,-C H (CH3)2),2.33(3H,s,-CH3),1.20(3H,d,J=7.2Hz,-CH3),1.06(3H,d,J=6.6Hz,-CH3). 13 C NMR (150MHz, CDCl3) δ141.6,138.0,134.5,133.2,131.4,131.1,130.1,129.6,128.7,125.9,54.0,39.1,21.3,17.6,13.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 17 H 20 S3Na 359.0568; Found 359.0573.

[0143] Example 20: Synthesis of Compound I-11

[0144] Referring to the general disulfide construction step E, compound III-03 is used as the starting material (wherein R 2SH was 2-methoxybenzenethiol), to give colorless oily liquid 1-11 (1.43 g, 88% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.81 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.2, 1.2, Hz, Ar-H), 7.41-7.36 (3H, m, Ar-H), 7.32 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 6.84-6.79 (2H, m, Ar-H), 4.09 (1H, d, J = 12.8 Hz, -CH2Ph), 4.01 (1H, d, J = 12.8 Hz, -CH2Ph), 3.79 (3H, s, -OCH3), 2.87 (1H, hept, J = 6.8 Hz, -C H H NMR (400 MHz, CDC13) δ 7.81 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.2, 1.2, Hz, Ar-H), 7.41-7.36 (3H, m, Ar-H), 7.32 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 6.84-6.79 (2H, m, Ar-H), 4.09 (1H, d, J = 12.8 Hz, -CH2Ph), 4.01 (1H, d, J = 12.8 Hz, -CH2Ph), 3.79 (3H, s, -OCH3), 2.87 (1H, hept, J = 6.8 Hz, -C 13 C NMR (150 MHz, CDC13) δ 160.1, 141.6, 134.6, 132.8, 131.4, 131.0, 128.7, 127.4, 125.9, 114.9, 55.6, 54.0, 39.1, 17.6, 13.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 17 H 20 O2S3Na 375.0518; Found 375.0522.

[0145] Example 21: Synthesis of compound 1-12

[0146] Reference to General Disulfide Construction Procedure E, compound III-03 was used as starting material (where R 2 SH was 2-methoxybenzenethiol), to give colorless oily liquid 1-11 (1.43 g, 88% for 2 steps). 1H NMR (600 MHz, CDC13) δ 7.84 (1H, d, J = 7.2 Hz, Ar-H), 7.59 (1H, dd, J = 7.2, 1.2 Hz, Ar-H), 7.48-7.44 (1H, m, Ar-H), 7.42-7.38 (2H, m, Ar-H), 7.25-7.23 (1H, m, Ar-H), 6.96 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 6.88 (1H, dd, J = 7.8, 0.6 Hz, Ar-H), 4.13 (1H, d, J = 13.2 Hz, -CH2Ph), 4.09 (1H, d, J = 13.2 Hz, -CH2Ph), 3.90 (3H, s, -OCH3), 2.97 (1H, hept, J = 7.2 Hz, -C H (CH3)2), 1.26 (3H, d, J = 7.2 Hz, -CH3), 1.12 (3H, d, J = 7.2 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 157.4, 141.6, 134.6, 131.4, 131.1, 129.6, 129.0, 128.7, 125.9, 124.5, 121.5, 111.2, 56.1, 54.1, 39.2, 17.7, 13.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 17 H 20 O2S3Na 375.0518; Found 375.0519.

[0147] Example 22: Synthesis of compound I-13

[0148] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (wherein R 2 SH is 3-methoxythiophenol) to give light yellow oily liquid I-13 (1.5 g, 92% for 2 steps). 1H NMR (600 MHz, CDC13) δ 7.82 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.37 (1H, td, J = 7.8, 1.8 Hz, Ar-H), 7.32 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.19 (1H, t, J = 7.8 Hz, Ar-H), 7.03-7.02 (2H, m, Ar-H), 6.75 (1H, ddd, J = 7.8, 2.4, 0.6, Hz, Ar-H), 4.19 (1H, d, J = 13.2 Hz, -CH2Ph), 4.02 (1H, d, J = 13.2 Hz, -CH2Ph), 3.79 (3H, s, -OCH3), 2.91 (1H, hept, J = 7.2 Hz, -CH3), 2.87 (1H, hept, J = 7.2 Hz, -CH3), 2.79 (1H, hept, J = 7.2 Hz, -CH3), 2.74 (1H, hept, J = 7.2 Hz, -CH3). H (CH3)2), 1.23 (3H, d, J = 6.6 Hz, -CH3), 1.11 (3H, d, J = 7.2 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 160.3, 141.6, 137.9, 134.5, 131.4, 131.1, 130.1, 128.8, 125.9, 120.4, 113.5, 113.4, 55.6, 54.2, 39.3, 17.5, 13.3. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 17 H 20 O2S3Na 375.0518; Found 375.0520.

[0149] Example 23: Synthesis of compound I-14

[0150] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (wherein R 2 SH is 3,4-dimethoxythiophenol) to give light yellow oily liquid I-14 (785 mg, 88% for 2 steps). 1H NMR (600 MHz, CDC13) δ 7.81 (1H, dd, J = 8.4, 1.2 Hz, Ar-H), 7.43 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.37 (1H, td, J = 7.8, 1.2, Hz, Ar-H), 7.32 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.02 (1H, dd, J = 7.8, 1.8 Hz, Ar-H), 6.99 (1H, d, J = 2.4 Hz, Ar-H), 6.76 (1H, d, J = 8.4 Hz, Ar-H), 4.12 (1H, d, J = 13.2 Hz, -CH2Ph), 4.00 (1H, d, J = 12.6 Hz, -CH2Ph), 3.85 (6H, s, -OMe), 2.86 (1H, hept, J = 6.6 Hz, -C H (CH3)2), 1.18 (3H, d, J = 7.2 Hz, -CH3), 1.08 (3H, d, J = 7.2 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 149.6, 149.5, 141.7, 134.7, 131.4, 131.1, 128.7, 127.7, 125.8, 123.7, 113.9, 111.6, 56.3, 54.1, 39.2, 17.5, 13.3. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 18 H 22 O3S3Na 405.0623; Found 405.0614.

[0151] Example 24: Synthesis of compound I-15

[0152] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (where R 2 SH was 4-nitrothiophenol) to give yellow oily liquid I-15 (440 mg, 52% for 2 steps). 1H NMR (600 MHz, CDC13) δ 8.09-8.06 (2H, m, Ar-H), 7.80 (1H, dd, J = 7.8, 0.6 Hz, Ar-H), 7.52-7.49 (2H, m, Ar-H), 7.44-7.39 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.32 (1H, td, J = 7.8, 1.2 Hz, Ar-H), 7.28 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 4.17 (1H, d, J = 13.2 Hz, -CH2Ph), 4.03 (1H, d, J = 13.2 Hz, -CH2Ph), 2.93 (1H, hept, J = 6.6 Hz, -CH(C H (CH3)2), 1.22 (1H, d, J = 6.6 Hz, -CH(C H 3)2), 1.19 (1H, d, J = 6.6 Hz, -CH(C H 3)2). 13 CNMR (150 MHz, CDC13) δ 146.5, 146.0, 134.4, 131.3, 129.2, 126.5, 126.1, 124.2, 54.8, 39.3, 17.2, 14.0. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 16 H 17 NO3S3Na 390.0263; Found 390.0263.

[0153] Example 25: Synthesis of compound I-16

[0154] Reference to the general dithioether construction procedure E, using compound III-03 as starting material (where R 2 SH is 4-trifluoromethylthiophenol) to give I-16 (766 mg, 85% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 8.09-8.06 (2H, m, Ar-H), 7.80 (1H, dd, J = 7.8, 0.6 Hz, Ar-H), 7.52-7.47 (2H, m, Ar-H), 7.42 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.33 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.28 (1H, dd, J = 8.0, 1.2 Hz, Ar-H), 4.12 (1H, d, J = 12.8 Hz, -CH2Ph), 4.01 (1H, d, J = 12.8 Hz, -CH2Ph), 2.91 (1H, hept, J = 6.8 Hz, -CH(C H(CH3)2),1.22(3H,d,J=6.8Hz,-CH3),1.15(3H,d,J=6.8Hz,-CH3). 13 C NMR (150MHz, CDCl3) δ141.6,134.4,131.3,131.2,129.2(q,J=32.5Hz),129.0,1 27.2, 126.0 (q, J = 3.4Hz), 126.0, 124.1 (q, J = 270.0Hz), 54.5, 39.2, 17.3, 13.7. 19 F NMR(565MHz,CDCl3)δ-62.54(br H).HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 17 H 17 F3OS3Na 413.0286; Found 413.0278.

[0155] Example 26: Synthesis of Compound I-17

[0156] Referring to the general disulfide construction step E, compound III-03 is used as the starting material (wherein R 2 SH is 4-fluorobenzenethiol) to give a light yellow oily liquid Ⅰ-17 (644 mg, 82% for 2 steps). 1 H NMR(400MHz,CDCl3)δ7.81(1H,dd,J=7.6,1.2Hz,Ar-H),7.43(1H,td,J=7.6,1.2Hz,Ar-H),7.41-7.37(2H,m,Ar-H),7.35(1H,dd,J=7.6,1.2Hz,Ar-H), 7.30(1H,dd,J=7.6,1.2Hz,Ar-H),6.99-6.93(2H,m,Ar-H),4.10(1H,d,J=12.8Hz,-CH2Ph),4.00(1H,d,J=12.8Hz,-CH2Ph),2.88(1H,hept,J=7.2Hz,-C H (CH3)2),1.20(3H,d,J=6.8Hz,-CH3),1.10(3H,d,J=6.8Hz,-CH3). 13CNMR (100 MHz, CDC13) δ 162.6 (d, J = 248.0 Hz), 141.6, 134.5, 131.94 (d, J = 3.2 Hz), 131.5 (d, J = 8.3 Hz), 131.4, 131.1, 128.8, 125.9, 116.4 (d, J = 22.2 Hz), 54.2, 39.1, 17.5, 13.4. 19 F NMR (565 MHz, CDC13) δ -113.77 (m) HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 16 H 17 FOS3Na 363.0318; Found 363.0316.

[0157] Example 27: Synthesis of compound I-18

[0158] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (where R 2 SH is 4-chlorothiophenol) to give pale yellow oily liquid I-18 (540 mg, 82% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.81 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.38 - 7.32 (3H, m, Ar-H), 7.29 (1H, dd, J = 7.6, 1.2 Hz, Ar-H), 7.25 - 7.21 (2H, m, Ar-H), 4.09 (1H, d, J = 12.8 Hz, -CH2Ph), 3.99 (1H, d, J = 12.8 Hz, -CH2Ph), 2.89 (1H, hept, J = 6.8 Hz, -CH(CH3)2), 2.82 (1H, hept, J = 6.8 Hz, -CH(CH3)2), 1.87 (3H, s, -CH3), 1.21 (3H, d, J = 6.8 Hz, -CH3), 1.12 (3H, d, J = 6.8 Hz, -CH3). H (CH3)2), 1.21 (3H, d, J = 6.8 Hz, -CH3), 1.12 (3H, d, J = 6.8 Hz, -CH3). 13 CNMR (100 MHz, CDC13) δ 141.6, 135.2, 134.4, 133.6, 131.3, 131.1, 129.8, 129.3, 128.9, 125.9, 54.3, 39.1, 17.4, 13.5. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 16 H 17 ClOS3Na 379.0022; Found 379.0018.

[0159] Example 28: Synthesis of Compound I-19

[0160] Referring to the general disulfide construction step E, compound III-03 is used as the starting material (wherein R 2 SH is 4-bromobenzenethiol) to give yellow oily liquid Ⅰ-19 (580 mg, 63% for 2 steps). 1 H NMR (400MHz, CDCl3) δ7.81 (1H, dd, J = 8.0, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.40-7.33 (3H, m, Ar-H), 7.31-7.26(3H,m,Ar-H),4.09(1H,d,J=12.8Hz,-CH2Ph),3.99(1H,d,J=12.8Hz,-CH2Ph),2.89(1H,hept,J=6.8Hz,-C H (CH3)2),1.21(3H,d,J=6.8Hz,-CH3),1.12(3H,d,J=6.8Hz,-CH3). 13 C NMR (150MHz, CDCl3) δ141.7,135.9,134.4,132.3,131.4,131.1,130.0,128.9,126.0,121.5,54.3,39.1,17.4,13.5.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 16 H 17 BrOS3Na422.9517; Found 422.9520.

[0161] Example 29: Synthesis of Compound I-20

[0162] Referring to the general disulfide construction step D, compound III-03 is used as the starting material (wherein R 2 SM is sodium methyl mercaptan), and a light yellow oily liquid Ⅰ-20 (1.0 g, 83% for 2 steps) was obtained. 1H NMR (600 MHz, CDC13) δ 7.86 (1H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.48 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.44 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.40 (1H, dd, J = 7.8, 1.8 Hz, Ar-H), 4.08 (1H, d, J = 13.2 Hz, -CH2Ph), 3.97 (1H, d, J = 12.6 Hz, -CH2Ph), 3.02 (1H, hept, J = 6.6 Hz, -C H (CH3)2), 2.19 (3H, s, -CH3), 1.29 (3H, d, J = 6.6 Hz, -CH3), 1.16 (3H, d, J = 6.6 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 141.4, 135.3, 131.0, 130.9, 128.5, 125.7, 54.0, 38.2, 23.1, 17.3, 13.2. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 11 H 16 OS3Na 283.0255; Found 283.0257.

[0163] Example 30: Synthesis of compound I-21

[0164] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (where R 2 SH is ethanethiol) to give light yellow oily liquid I-21 (538 mg, 85% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.86 (1H, dd, J = 7.6, 1.6, Hz, Ar-H), 7.51-7.38 (3H, m, Ar-H), 4.06 (1H, d, J = 12.8 Hz, -CH2Ph), 3.96 (1H, d, J = 12.8 Hz, -CH2Ph), 3.03 (1H, hept, J = 6.8 Hz, -C H (CH3)2), 2.51 (1H, q, J = 7.2 Hz, -CH2), 2.50 (1H, q, J = 7.2 Hz, -CH2) 1.30 (3H, d, J = 7.2 Hz, -CH3), 1.24 (3H, t, J = 7.2 Hz, -CH3), 1.16 (3H, d, J = 6.8 Hz, -CH3). 13C NMR (100 MHz, CDC13) δ 141.6, 135.5, 131.2, 130.9, 128.7, 125.9, 54.3, 39.4, 32.9, 17.6, 14.6, 13.4. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 12 H 18 OS3Na 297.0412; Found 297.0407.

[0165] Example 31: Synthesis of compound I-22

[0166] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (where R = H and R = CH3), and 4- methoxybenzyl mercaptan was used as the thiol (RSH = 4-methoxybenzyl mercaptan) to give I-23 (744 mg, 88% for 2 steps) as a colorless oil. 2 SH = benzyl mercaptan) to give I-22 (683 mg, 88% for 2 steps) as a colorless oil. 1 H NMR (400 MHz, CDC13) δ 7.79 (1H, dd, J = 8.0, 1.6 Hz, Ar-H), 7.42 (1H, td, J = 7.6, 1.6 Hz, Ar-H), 7.37 (1H, td, J = 7.6, 1.6 Hz, Ar-H), 7.31 - 7.17 (6H, m, Ar-H), 3.71 - 3.59 (4H, m, -CH2Ph), 2.89 (1H, hept, J = 6.8 Hz, -CH(CH3)2), 1.21 (3H, d, J = 6.8 Hz, -CH3), 1.09 (3H, d, J = 6.8 Hz, -CH3). H (CH3)2), 1.21 (3H, d, J = 6.8 Hz, -CH3), 1.09 (3H, d, J = 6.8 Hz, -CH3). 13 C NMR (100 MHz, CDC13) δ 141.5, 137.3, 135.4, 131.2, 131.0, 129.6, 128.9, 128.7, 127.8, 125.8, 54.3, 43.8, 39.2, 17.5, 13.5. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 17 H 20 OS3Na 359.0568; Found 359.0551.

[0167] Example 32: Synthesis of compound I-23

[0168] Referring to the general disulfide construction procedure E, compound III-03 was used as the starting material (where R = H and R = CH3), and 4- methoxybenzyl mercaptan was used as the thiol (RSH = 4-methoxybenzyl mercaptan) to give I-23 (744 mg, 88% for 2 steps) as a colorless oil. 2 SH = 4-methoxybenzyl mercaptan) to give I-23 (744 mg, 88% for 2 steps) as a colorless oil. 1H NMR (400 MHz, CDC13) δ 7.84 (1H, dd, J = 7.6, 1.6 Hz, Ar-H), 7.47 (1H, td, J = 7.2, 1.2 Hz, Ar-H), 7.42 (1H, td, J = 7.2, 1.6 Hz, Ar-H), 7.27 (1H, dd, J = 7.2, 1.2 Hz, Ar-H), 7.19 (2H, m, Ar-H), 6.85 (2H, m, Ar-H), 3.78 (3H, s, -OCH3), 3.75 (1H, d, J = 12.8 Hz, -CH2Ph), 3.70 (1H, d, J = 12.8 Hz, -CH2Ph), 3.69 (1H, d, J = 12.8 Hz, -CH2Ph), 3.66 (1H, d, J = 12.8 Hz, -CH2Ph), 2.95 (1H, m, -C H (CH3)2), 1.26 (3H, d, J = 6.8 Hz, -CH3), 1.14 (3H, d, J = 6.8 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 159.4, 141.6, 135.5, 131.2, 131.0, 130.7, 129.2, 128.7, 125.8, 114.3, 55.5, 54.3, 43.2, 39.2, 17.5, 13.5. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 18 H 22 O2S3Na 389.0674; Found 389.0679.

[0169] Example 33: Synthesis of compound I-24

[0170] Reference to General Disulfide Construction Procedure D, using compound III-04 as the starting material (wherein R 2 SM is sodium thiomethoxide), to give I-24 (250 mg, 75% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.80-7.78 (1H, m, Ar-H), 7.67-7.63 (2H, m, Ar-H), 7.47-7.37 (6H, m, Ar-H), 4.17 (1H, d, J = 13.2 Hz, -CH2Ph), 4.10 (1H, d, J = 13.2 Hz, -CH2Ph), 2.15 (3H, s, -CH3). 13C NMR (100 MHz, CDC13) δ 144.9, 144.3, 136.4, 131.6, 131.3, 131.2, 129.5, 129.3, 126.6, 125.8, 38.8, 23.3. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 14 H 14 OS3Na 317.0099; Found 317.0101.

[0171] Example 34: Synthesis of compound I-25

[0172] Referring to the general disulfide construction procedure D, using compound III-05 as the starting material (wherein R 2 SM is sodium benzenethiol), afforded I-25 (2.55 g, 91% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.82 (1H, dd, J = 8.0, 1.6 Hz, Ar-H), 7.47-7.36 (5H, m, Ar-H), 7.32 (1H, td, J = 7.6, 1.2 Hz, Ar-H), 7.29-7.24 (3H, m, Ar-H), 7.23-7.16 (3H, m, Ar-H), 4.16 (1H, d, J = 13.2 Hz, -CH2Ph), 4.04 (1H, d, J = 13.2 Hz, -CH2Ph), 2.34 (3H, s, -CH3). 13 C NMR (100 MHz, CDC13) δ 144.2, 141.9, 141.5, 136.7, 135.1, 131.4, 131.3, 130.2, 129.3, 129.2, 128.2, 127.4, 126.1, 126.0, 39.5, 21.6. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 20 H 18 OS3Na 393.0412; Found 393.0413.

[0173] Example 35: Synthesis of compound I-26

[0174] Referring to the general disulfide construction procedure E, using compound III-05 as the starting material (wherein R 2 SH is 4-methoxybenzenethiol), afforded I-26 (395 mg, 87% for 2 steps). 1H NMR (400 MHz, CDC13) δ 7.83 (1H, dd, J = 7.6, 1.6 Hz, Ar-H), 7.53 (2H, d, J = 8.0 Hz, Ar-H), 7.46-7.36 (3H, m, Ar-H), 7.25-7.23 (2H, m, Ar-H), 4.12 (1H, d, J = 13.2 Hz, -CH2Ph), 4.06 (1H, d, J = 13.2 Hz, -CH2Ph), 2.35 (3H, s, -CH3), 2.14 (3H, s, -CH3). 13 CNMR (150 MHz, CDC13) δ 160.0, 144.4, 141.8, 141.6, 135.4, 132.6, 131.4, 131.3, 130.2, 129.3, 127.6, 126.2, 126.0, 114.9, 55.6, 39.4, 21.6. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 21 H 20 O2S3Na 423.0518; Found 423.0510.

[0175] Example 36: Synthesis of compound I-27

[0176] Reference to General Disulfide Construction Procedure D, using compound III-05 as starting material (wherein R 2 SM is sodium thiomethoxide), afforded I-27 (300 mg, 85% for 2 steps). 1 H NMR (400 MHz, CDC13) δ 7.83 (1H, dd, J = 7.6, 1.6 Hz, Ar-H), 7.53 (2H, d, J = 8.0 Hz, Ar-H), 7.46-7.36 (3H, m, Ar-H), 7.25-7.23 (2H, m, Ar-H), 4.12 (1H, d, J = 13.2 Hz, -CH2Ph), 4.06 (1H, d, J = 13.2 Hz, -CH2Ph), 2.35 (3H, s, -CH3), 2.14 (3H, s, -CH3). 13 CNMR (150 MHz, CDC13) δ 160.0, 144.4, 141.8, 141.6, 135.4, 132.6, 131.4, 131.3, 130.2, 129.3, 127.6, 126.2, 126.0, 114.9, 55.6, 39.4, 21.6. HRMS (ESI-TOF) m / z: [M + Na] +Calcd for C 15 H 16 OS3Na331.0255;Found 331.0260.

[0177] Example 37: Synthesis of Compound I-28

[0178] Referring to the general disulfide construction step D, compound III-06 was used as the starting material (where R 2 SM is sodium thiophenolate), and a colorless liquid Ⅰ-28 (26 mg, 82% for 2 steps) was obtained. 1 H NMR(600MHz,CDCl3)δ7.69(1H,dd,J=7.8,1.2Hz,Ar-H),7.55-7.52(2H,m,Ar-H),7.40(1H,t,J=7.2Hz,Ar-H),7.33(2H,t ,J=7.8Hz,Ar-H),7.28(1H,d,J=7.2Hz,Ar-H),7.27-7.25(1H,m,Ar-H),4.16(2H,s,-CH2Ph),2.91(1H,hept,J=6.6Hz,-C H (CH3)2),2.73(1H,q,J=7.2Hz,-C H 2CH3), 2.72(1H,q,J=7.2Hz,-C H 2CH3),1.21(6H,m,-CH3),1.09(1H,d,J=7.2Hz,-CH3). 13 C NMR (151MHz, CDCl3) δ144.9,142.8,136.8,131.5,131.0,129.3,129.2,129.0 ,127.8,123.6,54.3,36.7,25.3,17.8,15.4,13.1.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 18 H 22 OS3Na 373.0725; Found373.0724.

[0179] Example 38: Synthesis of Compound I-29

[0180] Referring to the general disulfide construction step D, compound III-07 was used as the starting material (where R 2 SM is sodium thiophenolate), and a colorless oily liquid Ⅰ-29 (30 mg, 73% for 2 steps) was obtained. 1H NMR (600 MHz, CDC13) δ 8.41 (1H, s), 7.90-7.88 (1H, m), 7.75-7.73 (1H, m), 7.68 (1H, s), 7.58-7.56 (2H, m), 7.54-7.51 (2H, m), 7.42-7.38 (3H, m), 7.37-7.35 (2H, m), 7.18-7.15 (2H, m), 7.11-7.08 (1H, m), 4.13 (1H, d, J = 13.2 Hz), 4.06 (1H, d, J = 13.2 Hz). 13 C NMR (150 MHz, CDC13) δ 144.7, 141.0, 136.7, 134.3, 132.7, 131.7, 131.2, 130.8, 129.7, 129.1, 128.8, 128.4, 128.3, 127.9, 127.4, 127.2, 126.7, 40.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 23 H 18 OS3Na 429.0412; Found 429.0417.

[0181] Example 39: Synthesis of compound I-30

[0182] Referring to the general disulfide construction procedure D, compound III-08 was used as the starting material (wherein R 2 SM was sodium thiophenol), to give colorless liquid I-30 (55 mg, 55% for 2 steps). 1 H NMR (600 MHz, CDC13) δ 8.41 (1H, s), 7.90-7.88 (1H, m), 7.75-7.73 (1H, m), 7.68 (1H, s), 7.58-7.56 (2H, m), 7.54-7.51 (2H, m), 7.42-7.38 (3H, m), 7.37-7.35 (2H, m), 7.18-7.15 (2H, m), 7.11-7.08 (1H, m), 4.13 (1H, d, J = 13.2 Hz), 4.06 (1H, d, J = 13.2 Hz). 13C NMR (150MHz, CDCl3) δ141.1,136.6,134.9,131.5,131.4,129.2,128.9,128.1,127.4,125.5,66.9,64.3,64.0, 63.5(t,J=3.7Hz),63.2(t,J=3.4Hz),38.6,31.5(t,J=21.5Hz),31.4(t,J=21.6Hz).HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 32 H 24 F 26 O3S3Na 1069.0365; Found 1069.0363.

[0183] Example 40: Synthesis of Compound I-31

[0184] Referring to the general disulfide construction step D, compound III-09 was used as the starting material (where R 2 SM is sodium thiophenolate) to give a colorless liquid Ⅰ-31 (64 mg, 70% for 2 steps). 1 H NMR (400MHz, CDCl3) δ7.56-7.47(7H,m,Ar-H),7.32-7.28(2H,m,Ar-H),7.23 -7.20(1H,m,Ar-H),2.92-2.74(4H,m),2.21-2.10(1H,m),2.06-1.95(1H,m). 13 C NMR(150MHz, CDCl3)δ143.7,137.1,131.3,129.5,129.3,128.2,127.3,124.2,55.4,37.3,21.4.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 15 H 16 OS3Na331.0253;Found 331.0255.

[0185] Example 41: 100-gram preparation of compound I (taking the synthesis of compound I-02 as an example)

[0186]

[0187] After synthesis of II-01 according to the literature (J. Org. Chem., 2011, 76, 1513-1520), 170 g of II-01 was weighed into a reaction flask, 56 mL of acetic acid was added, and 395 mL of 30 wt% hydrogen peroxide aqueous solution was slowly added dropwise at room temperature using a constant pressure dropping funnel, and the reaction was carried out at room temperature until the reaction was complete. Subsequently, a sufficient amount of water was added to the reaction flask, and after stirring, white solid III-01 (171 g, 92%) was obtained by filtration under reduced pressure and lyophilization. The obtained III-01 was placed in a multi-necked reaction flask, 292 g of sodium thiosulfate pentahydrate and 0.9 L of water were added, and the reaction was carried out at 50°C for 4 hours until the conversion of compound III-01 was complete by TLC monitoring. Without any post-treatment operation, the above reaction solution was cooled to 0°C, 0.53 L of dichloromethane and p-methylphenyl mercaptan (124 g, 1.1 equivalents) were sequentially added, and a potassium carbonate (125 g, 1.0 equivalent, c 碳酸钾 = 0.8 M, v 水 = 1.13 L) was added dropwise to the reaction system (the dropping time was 2.5 hours). After the completion of the dropping, the reaction was continued for 30 minutes at 0°C, and then diluted with dichloromethane, washed with water three times, and the organic phase was combined, dried over anhydrous sodium sulfate, filtered and concentrated, and purified by recrystallization to obtain white solid I-02 (254 g, 91% for 2 steps).

[0188] The sugar donor (IV) involved in Examples 42-72, wherein:

[0189] Compounds IV-01 to IV-03, IV-05 to IV-09, IV-15, IV-17, IV-22 can be synthesized according to the similar method for synthesizing compound 2 in the literature (Org. Biomol. Chem., 2019, 17, 8379-8383);

[0190] Compounds IV-10, IV-11 were synthesized according to the literature (Org. Lett., 2020, 22, 6584-658, Org. Lett., 2005, 7, 4653-4656), respectively;

[0191] Compound IV-04 can be synthesized according to the following synthetic route:

[0192]

[0193] Commercially available peracetyl glucose S8 (1.0 g, 2.56 mmol), 2,6-dimethylbenzenethiol (430 mg, 3.07 mmol) were weighed into a multi-necked reaction flask, and 0.5 mL of acetic acid was added, and the reaction was carried out at 50°C for 4 hours until the conversion of compound IV-04 was complete by TLC monitoring. Without any post-treatment operation, the above reaction solution was cooled to 0°C, 0.53 L of dichloromethane and p-methylphenyl mercaptan (124 g, 1.1 equivalents) were sequentially added, and a potassium carbonate (125 g, 1.0 equivalent, c Molecular sieves (200 mg) and anhydrous dichloromethane (6.0 mL), triflic acid (180 μL, 2.05 mmol) was added dropwise under ice bath. After 2 h, the reaction was quenched by the addition of saturated sodium bicarbonate solution. The reaction was extracted with ethyl acetate, washed with water, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from ethyl acetate / petroleum ether to give white solid IV-04 (900 mg, 75%). Rf = 0.53 (petroleum ether-ethyl acetate 2:1). f = 0.53 (petroleum ether-ethyl acetate 2:1). 1 H NMR (600 MHz, CDC13) δ 7.15 (1H, dd, J = 8.4, 6.6 Hz, Ar-H), 7.09 (2H, d, J = 7.2 Hz, Ar-H), 5.15 (1H, t, J = 9.6 Hz), 5.08 (1H, t, J = 9.6 Hz), 5.03 (1H, t, J = 9.6 Hz), 4.39 (1H, d, J = 9.6 Hz, H-1), 4.13 (1H, dd, J = 12.0, 6.0 Hz), 4.02 (1H, dd, J = 12.0, 1.8 Hz), 3.49-3.47 (1H, m), 2.50 (6H, s, -CH3), 2.10 (3H, s, -COCH3), 2.00 (3H, s, -COCH3), 1.99 (3H, s, -COCH3), 1.98 (3H, s, -COCH3). 13 C NMR (150 MHz, CDC13) δ 170.8, 170.5, 169.6, 169.6, 144.3, 131.1, 129.6, 128.5, 88.7, 75.6, 74.2, 70.8, 68.7, 62.5, 22.5, 20.9, 20.8, 20.8, 20.8. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 22 H 28 O9SNa 491.1346; Found 491.1347.

[0194] Compound IV-12 can be synthesized according to the similar method of synthesis of compound 1c in the literature (Org. Lett., 2013, 15, 4904-4907);

[0195] Compound IV-13 can be synthesized according to the literature (J Carbohydr Chem. 1997, 16, 947-966);

[0196] Compound IV-14, IV-16, IV-18, IV-21 can be synthesized according to the literature (Org. Lett., 2004, 6, 3797-3800);

[0197] Compound IV-19 can be synthesized according to the literature (J Carbohydr Chem., 2007, 26, 349-368);

[0198] Compound IV-20 can be synthesized according to the literature (Synthesis, 2007, 9, 1412-1420);

[0199] Compound IV-23 can be synthesized according to the literature (Eur. J. Org. Chem., 2013, 6158-6166);

[0200] Compound IV-24 can be synthesized according to the following synthetic route:

[0201]

[0202] After synthesizing S9 according to the literature (Angew. Chem. Int. Ed. 2021, 60, 24859-24863), S9 (50 mg, 0.18 mmol) was weighed into anhydrous tetrahydrofuran (1.0 mL), and carbonylimidazole (60 mg, 0.37 mmol) was added. The reaction was carried out at room temperature for 10 hours. The tetrahydrofuran was distilled off, and the reaction solution was extracted with ethyl acetate, washed with dilute hydrochloric acid and saturated brine successively, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. To the crude product, 4-dimethylaminopyridine (4.5 mg, 0.04 mmol) and dichloromethane (1.0 mL) were added, and the mixture was cooled in an ice bath. Triethylamine (51 μL, 0.37 mmol) and benzoyl chloride (32 μL, 0.028 mmol) were added successively, and the mixture was moved to room temperature and reacted for 4 hours. The reaction solution was extracted with ethyl acetate, washed with water and saturated brine successively, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was recrystallized from dichloromethane / petroleum ether to obtain white flaky solid IV-24 (52 mg, 70%) R f = 0.38 (petroleum ether-ethyl acetate 2:1). 1H NMR (600 MHz, CDC13) δ 8.02 (2H, dd, J = 8.4, 1.2 Hz, Ar-H), 7.62-7.59 (1H, m, Ar-H), 7.46 (2H, t, J = 7.8 Hz, Ar-H), 7.36 (2H, d, J = 8.4 Hz, Ar-H), 7.09 (2H, d, J = 7.8 Hz, Ar-H), 5.16 (1H, dd, J = 8.4, 6.0 Hz, H-2), 4.98 (1H, dd, J = 7.2, 6.0 Hz, H-3), 4.91 (1H, d, J = 8.4 Hz, H-1), 4.67 (1H, dd, J = 7.2, 1.8 Hz, H-4), 3.98 (1H, qd, J = 6.6, 2.4 Hz, H-5), 2.32 (3H, s, -CH3), 1.47 (3H, d, J = 6.6 Hz, -CH3). 13 C NMR (100 MHz, CDC13) δ 165.0, 153.5, 139.1, 134.0, 133.9, 130.1, 130.1, 129.2, 128.8, 128.2, 85.2, 77.2, 76.57, 71.9, 71.2, 21.4, 16.5. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 21 H 20 O6SNa 423.0873; Found 423.0872.

[0203] Compound IV-25 can be synthesized according to the literature (Org. Biomol. Chem., 2019, 17, 2877-2882);

[0204] Compound IV-26 can be synthesized according to the literature (Carbohydr. Res., 2006, 341, 1702-1707);

[0205] Compound IV-27 can be synthesized according to the patent (CA2646407A1);

[0206] Compound IV-28, can be synthesized according to the following route:

[0207]

[0208] S11 (500 mg, 1.92 mmol) was weighed out, and anhydrous dichloromethane (3.7 mL) and p-methylthiophenol (287 mg, 2.30 mmol) were added under an argon atmosphere. The mixture was cooled to -40 °C, and boron trifluoride etherate (0.38 mL, 2.88 mmol) was slowly added. The reaction was allowed to proceed at -40 °C for 0.5 h, and then 1.0 mL of triethylamine was added to terminate the reaction. The reaction mixture was diluted with ethyl acetate and washed sequentially with water, saturated sodium bicarbonate, and 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 IV-28 (543 mg, 87%). f Rf = 0.51 (petroleum ether-ethyl acetate 4:1). 1 H NMR (600 MHz, CDCl3) δ 7.40 (2H, d, J = 7.8 Hz, Ar-H), 7.11 (2H, d, J = 7.8 Hz, Ar-H), 5.18-5.16 (2H, m), 4.85-4.81 (1H, m), 4.11-4.07 (1H, m), 2.31 (3H, s, -CH3), 2.06 (3H, s, -COCH3), 2.02 (3H, s, -COCH3). 13 C NMR (150 MHz, CDCl3) 169.9, 169.7 138.8, 134.3, 129.9, 128.0, 87.7, 78.6, 75.3, 74.3, 21.3, 20.8, 20.7, 19.5. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 16 H 20 O5SNa, 347.0924; Found 347.0922.

[0209] Compound IV-29 can be synthesized according to the literature (Eur. J. Org. Chem., 2021, 4525-4530)

[0210] The glycosyl acceptors (V) involved in Examples 42-72, wherein compounds V-02, V-09, V-14, V-17, V21~V25 are commercially available compounds;

[0211] Compound V-01 can be synthesized according to the literature (Tetrahedron Lett., 2017, 58, 2389-2392);

[0212] Compound V-03 can be synthesized according to the literature (Carbohydr. Res., 1982, 108, 97-102);

[0213] Compound V-04 can be synthesized according to the literature (J. Am. Chem. Soc, 2019, 141, 8509-8515);

[0214] Compound V-05 can be synthesized according to the literature (Chin. Chem. Lett., 2022, 33, 288-292);

[0215] Compound V-06 can be synthesized according to the literature (Carbohydr. Res., 2017, 452, 35-42);

[0216] Compound V-07 can be synthesized according to the literature (Angew. Chem. Int. Ed., 2014, 53, 8190-8194);

[0217] Compound V-08 can be synthesized according to the literature (Carbohydr. Res., 1981, 92, 154-156);

[0218] Compound V-10 can be synthesized according to the literature (Org. Chem. Front., 2019, 6, 3116-3120);

[0219] Compound V-11 can be synthesized according to the literature (J. Org. Chem., 2007, 72, 10268-10271);

[0220] Compound V-12 can be synthesized according to the literature (Bioorg. Med. Chem. Lett., 2020, 30, 127276);

[0221] Compound V-13 can be synthesized according to the literature (J. Am. Chem. Soc, 2019, 141, 11775-11780);

[0222] Compound V-15 can be synthesized according to the literature (Tetrahedron., 2003, 59, 3063-3087);

[0223] Compound V-16, can be synthesized according to the following synthetic route:

[0224]

[0225] To a solution of S10 (200 mg, 0.49 mmol) in dry pyridine (2.0 mL) was added acetic anhydride (0.23 mL, 2.46 mmol) dropwise under ice-bath. After addition, the mixture was allowed to warm to room temperature and the reaction was continued for 7 h. The reaction mixture was extracted with ethyl acetate and washed with dilute hydrochloric acid, saturated sodium bicarbonate solution, and saturated brine successively. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography to give V-17 (151 mg, 68%) as a colorless viscous liquid. Rf = 0.45 (petroleum ether-ethyl acetate 3:1). f = 0.45 (petroleum ether-ethyl acetate 3:1). 1 HNMR (600 MHz, CDC13) δ 4.58-4.53 (1H, m, 3a-H), 3.83 (1H, d, J = 1.2 Hz, 7a-H), 3.64 (3H, s, -OCH3), 2.36-2.18 (3H, m), 1.97 (3H, s, -COCH3), 1.97-1.58 (8H, m), 1.49-1.22 (10, m), 1.18-1.08 (4H, m), 1.02 (1H, td, J = 14.4, 3.6 Hz), 0.90 (3H, d, J = 6.6 Hz, 21-CH3), 0.89 (3H, s, 19-CH3), 0.64 (3H, s, 18-CH3). 13 C NMR (150 MHz, CDC13) δ 175.0, 171.0, 74.6, 68.7, 56.0, 51.7, 50.7, 42.9, 41.4, 39.8, 39.6, 35.6, 35.5, 35.3 35.2, 34.6, 33.0, 31.2, 31.2, 28.4, 26.9, 23.9, 23.0, 21.7, 20.8, 18.5, 12.0. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 27 H 44 O5Na 471.3081; Found 471.3078.

[0226] Compound V-18 can be synthesized according to the similar method as described in the literature (J. Agric. Food Chem., 2010, 58, 2138-2149) for the synthesis of compound 19;

[0227] Compound V-19 can be synthesized according to the literature (Angew. Chem. Int. Ed., 2018, 57, 15866-15870)

[0228] Compound V-20 can be synthesized according to the literature (Eur. J. Med. Chem., 2009, 44, 4112-412)

[0229] Example 42: Use of the compound of structural general formula (I) in the application of glycosylation reaction

[0230] The different substituted compounds of structural general formula (I) of the application are all suitable for the model glycosylation reaction of glycosyl donor IV-01 and glycosyl acceptor V-01, and can efficiently prepare disaccharide compound VI-01.

[0231]

[0232]

[0233]

[0234] Specific experimental operation: weigh the donor IV-01 (55 mg, 0.12 mmol), the acceptor V-01 (46 mg, 0.1 mmol) and the compound (I) (0.12 mmol), co-boil water with toluene, add powder molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) and pre-cool to -40℃. Under argon protection, add triflic anhydride (20 μL, 0.12 mmol) and react for 3 hours. Terminate with triethylamine. Extract the reaction solution with ethyl acetate, wash with water, saturated NaHCO3 solution and saturated brine in sequence, dry with anhydrous sodium sulfate, filter and concentrate under reduced pressure. Purify the crude product by silica gel column chromatography to obtain colorless syrup VI-01. 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 (2H, 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).

[0235] Example 43: Test of the reaction activity of the compound of the structure general formula (I) of the present application after storage at room temperature in air atmosphere

[0236]

[0237] The compound of the structure general formula (I) is stored at room temperature in air atmosphere for a certain period of time, and then used for the glycosylation coupling between the glycosyl donor IV-01 and the glycosyl acceptor V-01. Take the activated reagent I-01 and I-02 as examples:

[0238]

[0239] Specific experimental operation: weigh the donor IV-01 (55 mg, 0.12 mmol), the acceptor V-01 (46 mg, 0.1 mmol) and the compound (I-01 or I-02) (0.12 mmol), co-distil water with toluene, add powder molecular sieves (100 mg) and anhydrous dichloromethane (1.0 mL) are pre-cooled to -40°C. Under argon protection, add trifluoromethanesulfonic anhydride (20 μL, 0.12 mmol), and react for 3 hours. Terminate with triethylamine. Extract the reaction solution with ethyl acetate, wash with water, saturated NaHCO3 solution and saturated brine solution in sequence, dry over anhydrous sodium sulfate, filter and concentrate under reduced pressure. Purify the crude product by silica gel column chromatography to obtain colorless syrup VI-01.

[0240] Example 44: Application of the compound of structural general formula (I) of the present application in glycosylation reaction

[0241] The compound can effectively activate the different substituted sugar donors IV-01-IV-11 at C1 position, so as to make glycosylation reaction with the model sugar acceptor V-01, and efficiently prepare disaccharide compound VI-01. Take the activated reagent I-09 as an example:

[0242]

[0243]

[0244] Specific experimental operation: weigh any one of the donor IV-01-IV-11 (0.12 mmol), the acceptor V-01 (46 mg, 0.1 mmol) and the activated reagent I-09 (38.7 mg, 0.12 mmol), toluene azeotropically remove water, add powder Molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) are pre-cooled to -40℃. Under argon protection, triflic anhydride (20 μL, 0.12 mmol) is added, and the reaction is carried out for 3 hours. Terminate with triethylamine. The reaction solution is extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product is separated and purified by silica gel column chromatography to obtain colorless syrup compound VI-01.

[0245] Example 45: Application of the compound of structural general formula (I) of the present application in glycosylation reaction

[0246] The compound can activate the model sugar donor IV-01 at -78-30℃ temperature range, and synthesize disaccharide compound VI-01. Take the activated reagent I-11 as an example:

[0247]

[0248]

[0249] Specific experimental operation: weigh the sugar donor IV-01 (55 mg, 0.12 mmol), the sugar acceptor V-01 (46 mg, 0.1 mmol) and the activated reagent I-11 (42 mg, 0.12 mmol), toluene azeotropically remove water, add the newly activated powder Molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) were pre-cooled to a specific temperature (as shown in the above table). Under argon protection, triflic anhydride (20 μL, 0.12 mmol) was added, and the reaction was carried out for a specific time (as shown in the above table; in addition to the specific time in the above table, other reaction times can also be used, and the higher the reaction temperature, the shorter the corresponding reaction time). The reaction was terminated by adding Et3N. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, and saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain compound VI-01 in colorless syrup.

[0250] Example 1: Application of a compound represented by structural general formula (I) in a glycosylation reaction

[0251]

[0252]

[0253] Specific experimental operation: donor IV-01 (55 mg, 0.12 mmol), acceptor V-01 (46 mg, 0.1 mmol), and activated reagent VII (49 mg, 0.12 mmol) were weighed, and toluene was used to remove water by azeotropic distillation. New activated powdered Molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) were pre-cooled to a specific temperature. Under argon protection, triflic anhydride (20 μL, 0.12 mmol) was added, and the reaction was carried out for a specific time. The reaction was terminated by adding triethylamine. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, and saturated brine in sequence, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain compound VI-01 in colorless syrup.

[0254] Example 46: Application of a compound represented by structural general formula (I) in a glycosylation reaction

[0255] The compound can activate glycosyl donor IV-01 in halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, nitrile solvents, and ether solvents to synthesize disaccharide compound VI-01. Taking reagent I-09 as an example:

[0256]

[0257]

[0258] Specific experimental operation: donor IV-01 (55 mg, 0.12 mmol), acceptor V-01 (46 mg, 0.1 mmol), and activated reagent I-09 (38.7 mg, 0.12 mmol) were weighed, and toluene was used to remove water by azeotropic distillation. Powdered Molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) were pre-cooled to 0°C. Under argon protection, triflic anhydride (20 μL, 0.12 mmol) was added. After 1 hour, the reaction was continued at 30°C for 3 hours. The reaction was terminated by adding triethylamine. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain compound VI-02 as colorless syrup.

[0259] Example 47: Application of the compound of structural formula (I) of the present application in glycosylation reaction

[0260] Sub-chemical dose of the compound of formula (I) was used for activation of glycosyl donor IV-13, taking activation reagents I-01, I-02, I-03, I-04, I-07, I-09, I-11, I-20, I-24, I-25, I-28, I-29, I-30, and I-31 as examples.

[0261]

[0262]

[0263] Specific experimental operation: donor IV-13 (72 mg, 0.12 mmol), acceptor V-01 (46 mg, 0.1 mmol), and activation reagent of formula (I) (0.06 mmol) were weighed, and toluene was used for azeotropic dehydration. 2,6-di-tert-butyl-4-methylpyridine (25 mg, 0.12 mmol) and powdered molecular sieve (100 mg) were added, and the mixture was stirred at 0°C for 30 minutes. Triflic anhydride (20 μL, 0.12 mmol) was added under argon protection. After 1 hour, the reaction was continued at 30°C for 3 hours. The reaction was terminated by adding triethylamine. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain compound VI-02 as colorless syrup. Molecular sieve (100 mg) and anhydrous dichloromethane (1.0 mL) were pre-cooled to 0°C. Under argon protection, triflic anhydride (20 μL, 0.12 mmol) was added. After 1 hour, the reaction was continued at 30°C for 3 hours. The reaction was terminated by adding triethylamine. The reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine solution, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain compound VI-02 as colorless syrup. 1H NMR (400MHz, CDCl3) δ7.39-7.19(15H,m,Ar-H),4.99(1H,t,J=9.2Hz),4.95(1H,d,J=12.0Hz,-CH2Ph),4.92(1H,t,J=9.2Hz),4.86(1H,t,J =8.8Hz,H-2'),4.72-4.69(3H,m,-CH2Ph),4.56(1H,d,J=11.6Hz,-CH2Ph),4.57-4.54(2H,m,-CH2Ph),4.46(1H,d,J=7.6Hz,H-1'),4.39(1H ,d,J=12.0Hz,-CH2Ph),4.11(1H,dd,J=12.4,4.0Hz),3.87-3.78(3H,m),3.73(1H,dd,J=10.8,2.8Hz),3.59-3.55(2H,m),3.44(1H,dd,J=8. 8,3.6Hz,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).

[0264] Examples 48-72 Application of the compounds represented by the general structural formula (I) of the present invention in glycosidation reactions

[0265] Unless otherwise specified, the glycosidation reactions of Examples 47-71 can be performed according to the following three sets of standard operating procedures:

[0266] Reaction standard operating procedure A: weigh the glycosyl donor (1.2 equivalents), the acceptor (1.0 equivalents) and the compound represented by the general formula (I) (1.2 equivalents), and remove water by azeotropic addition of toluene. Molecular sieves (100 mg / mL in CH2Cl2 solution) and anhydrous dichloromethane (to achieve a receptor concentration of c = 0.1 M) were pre-cooled to -40°C or 0°C. Under argon protection, trifluoromethanesulfonic anhydride (1.2 equivalents) was added and the reaction was allowed to proceed until the starting material was completely converted. Triethylamine was added to terminate the reaction. The reaction solution was extracted with ethyl acetate, washed sequentially with water, saturated sodium bicarbonate solution, and saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was separated and purified by silica gel column chromatography to obtain the target glycosylated product.

[0267] Reaction standard operating procedure B: weigh the glycosyl donor (1.2 equivalents) and the compound represented by the general formula (I) (1.2 equivalents), remove water by azeotropic addition of toluene. Molecular sieves (100 mg / mL in CH2Cl2) and dry dichloromethane (to make the concentration of the donor c = 0.1 M) were pre-cooled to -40 °C. Under argon protection, triflic anhydride (1.2 eq) was added, and the reaction was continued until the donor was completely converted. Then a solution of the acceptor (1.0 eq) in dichloromethane (to make the concentration of the acceptor c = 0.1 M) was added, and the reaction was continued until the acceptor was completely converted. The reaction was terminated by the addition of triethylamine, and the reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give the target glycosidation product.

[0268] Reaction Standard Procedure C: The glycosyl donor (1.2 eq), the acceptor (1.0 eq), and the compound of general structure (I) (0.6 eq) were weighed and co-evaporated with toluene to remove water. 2,6-Di-tert-butyl-4-methylpyridine (1.2 eq) was added, and the mixture was dried over 3 A molecular sieves (100 mg / mL in CH2Cl2) and dry dichloromethane (to make the concentration of the donor c = 0.1 M) was pre-cooled to -40 °C. Under argon protection, triflic anhydride (1.2 eq) was added, and the reaction was continued until the donor was completely converted. Then a solution of the acceptor (1.0 eq) in dichloromethane (to make the concentration of the acceptor c = 0.1 M) was added, and the reaction was continued until the acceptor was completely converted. The reaction was terminated by the addition of triethylamine, and the reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give the target glycosidation product. Molecular sieves (100 mg / mL in CH2Cl2) and dry dichloromethane (to make the concentration of the donor c = 0.1 M) were pre-cooled to -40 °C. Under argon protection, triflic anhydride (1.2 eq) was added, and the reaction was continued until the donor was completely converted. Then a solution of the acceptor (1.0 eq) in dichloromethane (to make the concentration of the acceptor c = 0.1 M) was added, and the reaction was continued until the acceptor was completely converted. The reaction was terminated by the addition of triethylamine, and the reaction solution was extracted with ethyl acetate, washed with water, saturated sodium bicarbonate solution, saturated brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The crude product was purified by column chromatography on silica gel to give the target glycosidation product.

[0269] Example 48: Synthesis of oxyglycoside VI-03

[0270]

[0271] Referring to Reaction Standard Procedure A, colorless syrup VI-03 (15.4 mg, 85%) was obtained. Rf= 0.30 (petroleum ether-ethyl acetate 2:1). f 1 ​H NMR (600 MHz, CDC13) δ 7.96 (1H, d, J = 7.2 Hz, Ar-H), 7.52 (1H, t, J = 7.2 Hz Ar-H), 7.36 (2H, t, J = 7.8 Hz, Ar-H), 7.33-7.30 (4H, m, Ar-H), 7.27-7.18 (9H, m, Ar-H), 7.14-7.13 (2H, m, Ar-H), 5.25 (1H, t, J = 5.4 Hz), 5.15 (1H, d, J = 5.4 Hz), 4.89 (1H, dd, J = 7.8, 4.2 Hz), 4.72 (1H, d, J = 11.4 Hz), 4.60 (1H, dd, J = 7.8, 2.4 Hz), 4.56 (1H, d, J = 8.4 Hz, H-1'), 4.56 (3H, d, J = 11.4 Hz), 4.37 (1H, d, J = 11.4 Hz), 4.21 (1H, d, J = 11.4 Hz), 4.12 (1H, d, J = 2.4 Hz, H-1), 3.89-3.84 (2H, m), 3.81 (1H, dd, J = 9.6, 2.4 Hz), 3.74-3.70 (2H, m), 3.58 (1H, dd, J = 9.6, 5.4 Hz), 3.30 (3H, s, -OCH3), 1.36 (3H, d, J = 6.6 Hz, -CH3). 13 C NMR (150 MHz, CDC13) δ 164.8, 153.7, 139.0, 138.6, 138.6, 133.8, 130.2, 129.3, 128.7, 128.5, 128.5, 128.5, 128.1, 127.9, 127.8, 127.7, 127.7, 127.7, 100.4, 98.6, 78.4, 76.6, 75.8, 75.6, 73.9, 73.8, 73.7, 71.3, 69.5, 69.2, 67.7, 55.5, 16.5. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 42 H 44 O 12 Na 763.2725; Found 763.2718.

[0272] Example 49: Synthesis of oxime VI-04

[0273]

[0274] Referring to the reaction standard operating procedure B, 2,6-di-tert-butyl-4-methylpyridine (14 mg, 1.2 equiv.) was added along with the donor and activating reagent to give Ⅵ-04 (38 mg, 96%) as a white foamy solid. Rf = 0.23 (petroleum ether-ethyl acetate 4:1). f = 0.35 (petroleum ether-ethyl acetate 10:1). 1 H NMR (400 MHz, CDC13) δ 7.49 (1H, dd, J = 7.6, 2.0 Hz, Ar-H), 7.43-7.25 (13H, m, Ar-H), 5.88 (1H, d, J = 4.0 Hz, H-1), 5.61 (1H, s), 4.86 (1H, d, J = 12.0 Hz), 4.81 (1H, d, J = 11.6 Hz), 4.75 (1H, d, J = 12.8 Hz), 4.62 (1H, d, J = 12.4 Hz), 4.55 (1H, s, H-1'), 4.43-4.38 (2H, m), 4.30-4.26 (3H, m), 4.21 (1H, t, J = 9.6 Hz), 4.11 (1H, dd, J = 8.8, 6.4 Hz), 4.04 (1H, dd, J = 8.4, 6.0 Hz), 3.90 (1H, t, J = 10.0 Hz), 3.85 (1H, d, J = 2.0 Hz), 3.60 (1H, dd, J = 10.0, 3.2 Hz), 3.34-3.28 (1H, m), 1.48 (3H, s), 1.42 (3H, s), 1.32 (3H, s), 1.29 (3H, s).

[0275] Example 50: Synthesis of oxime Ⅵ-05

[0276]

[0277] Referring to the reaction standard operating procedure B, 2,6-di-tert-butyl-4-methylpyridine (15 mg, 1.2 equiv.) was added along with the donor and activating reagent to give Ⅵ-05 (32 mg, 92%) as a white foamy solid. Rf = 0.35 (petroleum ether-ethyl acetate 10:1). f = 0.35 (petroleum ether-ethyl acetate 10:1). 1H NMR (400 MHz, CDC13) δ 7.49 (4H, dd, J = 8.0, 2.0 Hz, Ar-H), 7.39-7.23 (11H, m, Ar-H), 5.60 (1H, s, Benzylidene-H), 5.01 (1H, d, J = 12.4 Hz, -CH2Ph), 4.92 (1H, d, J = 12.4 Hz, -CH2Ph), 4.74 (1H, s, H-1), 4.66 (1H, d, J = 12.4 Hz, -CH2Ph), 4.57 (1H, d, J = 12.4 Hz, -CH2Ph), 4.24 (1H, dd, J = 10.4, 4.8 Hz H-6a), 4.19 (1H, t, J = 9.6 Hz, H-4), 3.92 (1H, t, J = 10.4 Hz, H-6b), 3.76 (1H, d, J = 2.4 Hz, H-2), 3.58 (1H, dd, J = 10.0, 3.2 Hz, H-3), 3.33-3.27 (1H, m), 2.15 (3H, br s), 1.85-1.73 (6H, m), 1.66-1.58 (6H, m).

[0278] Example 51: Synthesis of oxime Ⅵ-06

[0279]

[0280] Following the reaction standard procedure A, colorless syrup Ⅵ-06 (37 mg, 93%) was obtained. Rf = 0.11 (petroleum ether-acetone 3:1). f 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).

[0281] Example 52: Synthesis of oxime VI-07

[0282]

[0283] Referring to the reaction standard operating procedure A, additional 2,6-di-tert- butyl-4-methylpyridine DTBMP (11 mg, 1.2 eq) gave oxime VI-07 (28 mg, 91%) as colorless syrup. 1 H NMR (400 MHz, CDC13) δ 1H NMR (400 MHz, CDC13) δ 7.33-7.22 (15H, m, Ar-H), 5.50 (1H, dd, J = 2.8, 53.2 Hz, H-1), 5.13 (1H, t, J = 8.8, 8.4 Hz), 4.94 (3H, m), 4.80 (3H, m, PhCH2), 4.67 (1H, d, J = 12.0 Hz, PhCH2), 4.53 (1H, d, J = 10.8 Hz, PhCH2), 4.48 (1H, d, J = 6.8 Hz), 4.09 (1H, dd, J = 4.8, 11.6 Hz, H-6a), 4.00 (1H, dd, J = 1.6, 11.2 Hz, H-6b), 3.95 (1H, t, J = 9.2, 9.6 Hz), 3.90 (1H, m, H-5), 3.76 (1H, dd, J = 3.6, 11.2 Hz, H-5a'), 3.57 (1H, t, J = 9.6, 10.0 Hz), 3.50 (1H, ddd, J = 2.4, 9.6, 12.0 Hz, H-2), 3.29 (1H, dd, J = 8.8, 11.6 Hz, H-5b'), 2.02 (3H, s, CH3), 2.02 (3H, s, CH3), 1.99 (3H, s, CH3), 1.92 (3H, s, CH3). 13 C NMR (101 MHz, CDC13) δ 170.33, 170.00, 169.46, 138.58, 138.07, 137.76, 128.78, 128.64, 128.32, 128.26, 128.19, 128.10, 127.94, 106.77 (d, J = 230 Hz, C-1), 100.61, 81.48, 79.51 (d, J = 20 Hz), 76.69, 76.00, 75.34, 73.79, 72.44, 72.40 (d, J = 6 Hz), 71.77, 70.96, 68.91, 67.19, 20.94, 20.91, 20.84. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 38 H 43 O 12 FNa 733.2631; Found 733.2616.

[0284] Example 53: Synthesis of oxime Ⅵ-08

[0285]

[0286] Following the reaction standard procedure B, colorless syrup Ⅵ-08 (37 mg, 95%) was obtained. R f= 0.33 (petroleum ether-ethyl acetate 3: 1). R f = 0.33 (petroleum ether-ethyl acetate 3: 1). 1 H NMR (600 MHz, CDC13) δ 7.92 (2H, dd, J = 6.6, 1.8 Hz, Ar-H), 7.90 (2H, dd, J = 7.2, 1.2 Hz, Ar-H), 7.80 (2H, dd, J = 7.2, 1.2 Hz, Ar-H), 7.50 (1H, t, J = 7.8 Hz, Ar-H), 7.44-7.34 (6H, m, Ar-H), 7.30-7.22 (15H, m, Ar-H), 7.15-7.14 (2H, m, Ar-H), 5.80 (1H, t, J = 9.6 Hz), 5.53 (1H, dd, J = 9.6, 7.8 Hz, H-2'), 5.32 (1H, t, J = 9.6 Hz), 4.91 (1H, d, J = 10.8 Hz, -CH2Ph), 4.86 (1H, d, J = 10.8 Hz, -CH2Ph), 4.83 (1H, d, J = 7.8 Hz, H-1'), 4.69 (1H, d, J = 10.8 Hz, -CH2Ph), 4.64 (1H, d, J = 10.2 Hz, -CH2Ph), 4.63 (1H, d, J = 10.8 Hz, -CH2Ph), 4, 51 (1H, d, J = 7.8 Hz, H-1), 4.43 (1H, d, J = 10.8 Hz, -CH2Ph), 4.22 (1H, dd, J = 15.6, 2.4 Hz), 4.17-4, 14 (2H, m), 3.84-3.80 (1H, m), 3.68 (1H, dd, J = 10.8, 6.0 Hz), 3.59 (1H, t, J = 9.0 Hz), 3.48-3.46 (1H, m), 3.39 (1H, t, J = 9.6 Hz), 3.37 (1H, t, J = 9.0 Hz), 2.44 (1H, t, J = 2.4 Hz), 1.36 (3H, d, J = 6.0 Hz, H-6'). 13C NMR (150 MHz, CDC13) δ 166.1, 165.6, 165.2, 138.7, 138.5, 138.2, 133.5, 133.3, 133.3, 130.0, 129.9, 129.5, 129.3, 129.1, 128.6, 128.6, 128.6, 128.5, 128.5, 128.0, 128.0, 127.9, 127.9, 127.8, 101.5, 101.1, 84.6, 82.0, 79.3, 77.7, 75.8, 75.1, 75.0, 74.9, 74.7, 74.1, 73.2, 72.3, 70.8, 68.4, 56.1, 17.8. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 57 H 54 O 13 Na 969.3457; Found 969.3451.

[0287] Example 54: Synthesis of oxime Ⅵ-09

[0288]

[0289] Referring to the reaction standard operating procedure C, colorless syrup Ⅵ-09 (42 mg, 93%) was obtained. Rf = 0.23 (petroleum ether-ethyl acetate 8: 1). f = 0.23 (petroleum ether-ethyl acetate 8: 1). 1H NMR (400 MHz, CDC13) δ 7.95 (2H, d, J = 8.0, 1.2, Ar-H), 7.42 (1H, tt, J = 7.6, 1.2 Hz, Ar-H), 7.32 - 7.20 (20H, m, Ar-H), 7.10 - 7.07 (2H, m, Ar-H), 5.08 (1H, dd, J = 6.4, 3.2 Hz, H-2'), 4.92 (1H, d, J = 6.4 Hz, H-1'), 4.89 (1H, d, J = 11.2 Hz, -CH2Ph), 4.72 (1H, d, J = 12.0 Hz, -CH2Ph), 4.71 (1H, d, J = 11.2 Hz, -CH2Ph), 4.58 (1H, d, J = 12.0 Hz, -CH2Ph), 4.58 (1H, d, J = 12.0 Hz, -CH2Ph), 4.51 (1H, d, J = 10.8 Hz, -CH2Ph), 4.49 (1H, d, J = 12.0 Hz, -CH2Ph), 4.47 (1H, d, J = 3.6 Hz, H-1), 4.16 - 4.12 (1H, m), 3.95 - 3.74 (5H, m), 3.70 - 3.65 (3H, m), 3.47 - 3.42 (2H, m), 3.21 (3H, s, -OCH3), 0.82 (9H, s), 0.81 (9H, s), 0.01 (3H, s), 0.04 (3H, s), 0.02 (3H, s), -0.01 (3H, s). 13 C NMR (100 MHz, CDC13) δ 165.4, 139.1, 138.6, 138.4, 138.4, 133.1, 130.1, 130.0, 128.6, 128.5, 128.5, 128.5, 128.4, 128.3, 128.0, 128.0, 127.8, 127.7, 127.7, 127.6, 100.2, 98.2, 82.2, 79.9, 79.5, 77.7, 75.7, 75.1, 75.1, 73.6, 73.5, 71.2, 71.1, 69.8, 67.9, 55.2, 26.1, 18.2, 18.1, -3.8, -4.1, -4.1, -4.3. HRMS (ESI-TOF) m / z: [M + Na] Calcd for C + Calcd for C 60 H 80 O 12 Si2Na 1071.5081; Found 1071.5065.

[0290] Example 55: Synthesis of oxime Ⅵ-10

[0291]

[0292] Referring to the reaction standard operating procedure C, the acceptor was added after triflic anhydride at -40 °C to give colorless syrup VI-10 (27 mg, 81%). Rf= 0.43 (petroleum ether-ethyl acetate 2: 1). f = 0.43 (petroleum ether-ethyl acetate 2: 1). 1 H NMR (400 MHz, CDC13) δ 7.32-7.21 (13H, m, Ar-H), 7.11 (2H, m, Ar-H), 6.95-6.91 (2H, m, Ar-H), 6.74-6.70 (2H, m, Ar-H), 5.34 (1H, dd, J = 3.2, 1.6 Hz), 5.25 (1H, t, J = 9.6 Hz), 5.19 (1H, t, J = 9.6 Hz), 5.03 (1H, t, J = 9.6 Hz), 4.88 (1H, d, J = 7.6 Hz, H-1), 4.84 (1H, d, J = 1.6 Hz, H-1'), 4.83 (1H, d, J = 10.4 Hz), 4.67 (1H, d, J = 10.8 Hz), 4.63 (1H, d, J = 12.0 Hz), 4.51 (1H, d, J = 10.8 Hz), 4.47 (1H, d, J = 10.8 Hz), 4.46 (1H, d, J = 12.0 Hz), 3.91 (1H, dd, J = 9.2, 3.2 Hz), 3.85 (1H, t, J = 9.2 Hz), 3.81-3.69 (4H, m), 3.65 (1H, dd, J = 10.8, 1.6 Hz), 3.54-3.51 (1H, m), 3.53 (3H, s, -OCH3), 2.12 (3H, s, -COCH3), 2.06 (3H, s, -COCH3), 2.02 (3H, s, -COCH3), 2.00 (3H, s, -COCH3). 13 C NMR (100 MHz, CDC13) δ 170.6, 170.5, 169.6, 169.5, 156.0, 151.1, 138.7, 138.3, 138.1, 128.6, 128.5, 128.4, 128.2, 127.9, 127.8, 127.8, 127.6, 119.4, 114.8, 100.8, 97.8, 78.4, 75.2, 74.3, 73.5, 73.1, 72.8, 72.3, 71.7, 71.5, 69.2, 68.9, 68.8, 66.3, 55.6, 21.3, 20.9, 20.8. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 48 H 54 O 16Na 909.3304; Found 909.3267.

[0293] Example 56: Synthesis of oxime Ⅵ-11

[0294]

[0295] Referring to the reaction standard operating procedure C, colorless syrup Ⅵ-11 (29 mg, 93%) was obtained. Rf = 0.29 (petroleum ether-ethyl acetate 3:1). f = 0.29 (petroleum ether-ethyl acetate 3:1). 1 H NMR (400 MHz, CDC13) δ 8.09 (2H, d, J = 7.2 Hz, Ar-H), 7.69 (1H, t, J = 3.6 Hz, Ar-H), 7.55 (2H, t, J = 8.0 Hz, Ar-H), 7.47 - 7.39 (9H, m, Ar-H), 7.29 (1H, td, J = 7.6, 0.8 Hz, Ar-H), 7.26 (3H, m, Ar-H), 7.17 (1H, t, J = 7.6 Hz, Ar-H), 5.43 - 5.35 (3H, m), 5.16 (1H, dd, J = 3.2, 10.4 Hz), 5.06 (1H, d, J = 13.2 Hz, -CH2Ph), 4.97 (1H, d, J = 13.2 Hz, -CH2Ph), 4.93 (1H, d, J = 10.8 Hz, -CH2Ph), 4.87 (1H, d, J = 11.2 Hz, -CH2Ph), 4.84 (1H, d, J = 9.6 Hz, -CH2Ph), 4.81 (1H, d, J = 12.0 Hz, -CH2Ph), 4.78 (1H, d, J = 8.4 Hz, H-1), 4.68 (1H, d, J = 8.4 Hz, H-1'), 4.32 (1H, dd, J = 2.4, 12.4 Hz), 4.04 (1H, d, J = 11.2 Hz), 3.95 - 3.85 (3H, m), 3.57 - 3.55 (1H, m), 3.37 (1H, m, -CH2Ph), 3.34 (1H, m, -CH2Ph), 3.28 (1H, m, -CH2Ph), 3.26 (1H, m, -CH2Ph), 3.24 (1H, m, -CH2Ph), 3.22 (1H, m, -CH2Ph), 3.20 (1H, m, -CH2Ph), 3.18 (1H, m, -CH2Ph), 3.16 (1H, m, -CH2Ph), 3.14 (1H, m, -CH2Ph), 3.12 (1H, m, -CH2Ph), 3.10 (1H, m, -CH2Ph), 3.08 (1H, m, -CH2Ph), 3.06 (1H, m, -CH2Ph), 3.04 (1H, m, -CH2Ph), 3.02 (1H, m, -CH2Ph), 3.00 (1H, m, -CH2Ph), 2.99 (1H, m, -CH2Ph), 2.97 (1H, m, -CH2Ph), 2.95 (1H, m, -CH2Ph), 2.94 (1H, m, -CH2Ph), 2.92 (1H, m, -CH2Ph), 2.90 (1H, m, -CH2Ph), 2.88 (1H, m, -CH2Ph), 2.86 (1H, m, -CH2Ph), 2.84 (1H, m, -CH2Ph), 2.82 (1H, m, -CH2Ph), 2.80 (1H, m, -CH2Ph), 2.78 (1H, m, -CH2Ph), 2.76 (1H, m, -CH2Ph), 2.74 (1H, m, -CH2Ph), 2.72 (1H, m, -CH2Ph), 2.70 (1H, m, -CH2Ph), 2.68 (1H, m, -CH2Ph), 2.66 (1H, m, -CH2Ph), 2.64 (1H, m, -CH2Ph), 2.62 (1H, m, -CH2Ph), 2.60 (1H, m, -CH2Ph), 2.58 (1H, m, -CH2Ph), 2.56 (1H, m, -CH2Ph), 2.54 (1H, m, -CH2Ph), 2.52 (1H, m, -CH2Ph), 2.50 (1H, m, -CH2Ph), 2.48 (1H, m, -CH2Ph), 2.46 (1H, m, -CH2Ph), 2.44 (1H, m, -CH2Ph), 2.42 (1H, m, -CH2Ph), 2.40 (1H, m, -CH2Ph), 2.38 (1H, m, -CH2Ph), 2.36 (1H, m, -CH2Ph), 2.34 (1H, m, -CH2Ph), 2.32 (3H, s, -COCH3), 2.29 (3H, s, -COCH3), 2.13 (3H, s, -COCH3), 1.35 (3H, d, J = 6.4 Hz), 1.31 (3H, d, J = 6.8 Hz), 1.30 (3H, d, J = 6.4 Hz). H

[0296] Example 57: Synthesis of oxime Ⅵ-12

[0297]

[0298] ​Referring to the reaction standard operating procedure C, colorless syrup VI-12 (30 mg, 91%) was obtained.R f = 0.32 (petroleum ether-EtOAc 4:1). f = 0.32 (petroleum ether-EtOAc 4:1). 1 H NMR (400 MHz, CDC13) δ 8.00 (4H, td, J = 8.0, 0.8 Hz, Ar-H), 7.84 (2H, dd, J = 8.4, 1.2 Hz, Ar-H), 7.58-7.54 (1H, m, Ar-H), 7.51-7.46 (2H, m, Ar-H), 7.41 (2H, t, J = 8.0 Hz, Ar-H), 7.34-7.26 (4H, m, Ar-H), 5.77-5.70 (3H, m), 4.84 (1H, s), 4.71 (1H, td, J = 6.8, 4.8 Hz), 4.64 (1H, dd, J = 11.6, 4.8 Hz), 4.55 (1H, dd, J = 11.2, 6.4 Hz), 4.20-4.17 (1H, m), 4.09-4.07 (1H, m), 3.64-3.58 (2H, m), 3.34 (3H, s, -OCH3), 1.52 (3H, s, -CH3), 1.30 (3H, s, -CH3), 1.29 (3H, d, J = 6.0 Hz, -CH3).

[0299] Example 58: Synthesis of oxime VI-13

[0300]

[0301] Referring to the reaction standard operating procedure C, colorless syrup VI-13 (30 mg, 98%) was obtained.R f = 0.25 (petroleum ether-EtOAc 4:1). 1H NMR (400 MHz, CDC13) δ 7.45-7.42 (2H, m, Ar-H), 7.36-7.31 (3H, m, Ar-H), 5.59 (1H, s, -CHPh), 5.34-5.29 (1H, m, H-3'), 5.11 (1H, s, H-1), 5.03 (1H, d, J = 1.2 Hz, H-4'), 4.96 (1H, d, J = 2.8 Hz, H-1'), 4.46 (1H, d, J = 4.4 Hz, H-2), 4.27-4.22 (2H, m, H-5, H-5), 3.98 (1H, t, J = 9.2 Hz, H-4), 3.91 (1H, td, J = 10.0, 4.0 Hz, H-6a), 3.86 (1H, t, J = 10.0 Hz, H-6b), 3.42 (1H, dd, J = 4.4, 9.2 Hz, H-3), 3.36 (3H, s, -OCH3), 2.10 (3H, s, -COCH3), 2.03 (1H, td, J = 12.4, 3.6 Hz, H-2a'), 1.95 (3H, s, -COCH3), 1.87 (1H, dd, J = 4.8, 12.0 Hz, H-2b'), 0.82 (1H, d, J = 6.4 Hz, H-6').

[0302] Example 59: Synthesis of oxime Ⅵ-14

[0303]

[0304] Referring to reaction standard procedure C, colorless syrup Ⅵ-14 (19 mg, 95%) was obtained. Rf = 0.24 (petroleum ether-ethyl acetate 1.5:1). f = 0.24 (petroleum ether-ethyl acetate 1.5:1). 1H NMR (400 MHz, CDC13) δ 8.30 (2H, d, J = 8.8 Hz, Ar-H), 8.05 (2H, d, J = 8.8 Hz, Ar-H), 6.32 (1H, s, -NH), 5.24-5.18 (2H, m, H-3, H-4), 5.08 (1H, d, J = 2.8 Hz, H-1), 4.65 (1H, d, J = 3.6 Hz, H-1'), 4.13-4.08 (1H, m, H-5), 3.83-3.76 (1H, m, H-5'), 3.34 (3H, s, -OCH3), 3.09 (1H, d, J = 9.2 Hz, H-4'), 2.13 (3H, s, -COCH3), 2.07-1.93 (3H, m, H-2a', H-2a, H-2b), 2.01 (3H, s, -COCH3), 1.65 (1H, dd, J = 4.0, 14.4 Hz, H-2b'), 1.35 (3H, s, -CH3), 1.24 (3H, d, J = 6.8 Hz, H-6'), 1.09 (3H, d, J = 6.8 Hz, H-6).

[0305] Example 60: Synthesis of oxylucoside VI-15 (This example illustrates the synthesis of one glycosidic linkage)

[0306]

[0307] Following the reaction standard procedure C, colorless syrup VI-15 (56 mg, 96%) was obtained. Rf = 0.21 (petroleum ether-ethyl acetate 5:1). f = 0.21 (petroleum ether-ethyl acetate 5:1). 1H NMR (400 MHz, CDC13) δ 7.97-7.04 (30H, m, Ar-H), 5.54 (1H, s, Benzylidene-H), 5.03 (1H, d, J = 10.4 Hz, -CH2Ph), 4.89 (1H, d, J = 10.8 Hz, -CH2Ph), 4.88 (1H, d, J = 3.6 Hz), 4.88 (1H, d, J = 9.2 Hz, -CH2Ph), 4.85 (1H, d, J = 10.4 Hz, -CH2Ph), 4.84 (1H, d, J = 3.6 Hz), 4.79 (1H, d, J = 12.0 Hz, -CH2Ph), 4.74 (1H, d, J = 10.4 Hz, -CH2Ph), 4.70 (1H, d, J = 12.0 Hz, -CH2Ph), 4.56 (1H, d, J = 10.8 Hz, -CH2Ph), 4.36-4.27 (3H, m), 4.16-4.08 (3H, m), 3.87-3.81 (2H, m), 3.70 (1H, t, J = 10.0 Hz), 3.61-3.54 (3H, m), 3.44 (3H, s). 13 C NMR (100 MHz, CDC13) δ 166.3, 138.8, 138.5, 138.4, 138.1, 137.6, 133.2, 130.3, 130.0, 129.2, 128.9, 128.7, 128.7, 128.6, 128.5, 128.5, 128.4, 128.2, 128.2, 128.2, 128.0, 128.0, 127.9, 126.2, 101.5, 97.3, 94.4, 82.9, 82.3, 79.6, 77.9, 76.1, 75.8, 75.3, 74.5, 73.2, 69.3, 69.1, 63.2, 62.4, 55.2. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 55 H 56 O 12 Na 931.3664; Found 931.3726.

[0308] Example 61: Synthesis of oxysyl VI-16 (This example illustrates the synthesis of two glycosidic bonds)

[0309]

[0310] Reference to reaction standard operating procedure C, donor IV-16 (48 mg, 0.080 mmol), acceptor V-10 (14 mg, 0.0034 mmol), activating reagent I-02 (12.3 mg, 0.040 mmol), 2,6-di-tert-butyl-4-methylpyridine (16 mg, 0.080 mmol) and triflic anhydride (7 μL, 0.040 mmol). Colorless syrup VI-16 (35.9 mg, 81%) was obtained. Rf= 0.14 (petroleum ether-ethyl acetate 2:1). f = 0.14 (petroleum ether-ethyl acetate 2:1). 1 H NMR (400 MHz, CDC13) δ 7.35 - 7.08 (40H, m, Ar-H), 5.35 (1H, t, J = 10.4 Hz), 5.33 (1H, t, J = 10.4 Hz), 5.07 (1H, d, J = 12.0 Hz), 5.03 (1H, d, J = 12.0 Hz), 4.94 (1H, d, J = 11.2 Hz), 4.93 (1H, d, J = 11.6 Hz), 4.91 (1H, d, J = 11.2 Hz), 4.79 (1H, d, J = 9.6 Hz), 4.67 (1H, d, J = 12.4 Hz), 4.60 (1H, d, J = 12.4 Hz), 4.57 (1H, d, J = 4.4 Hz, H-1a), 4.54 - 4.46 (4H, m), 4.45 (1H, d, J = 8.4 Hz, H-1b), 4.41 (1H, d, J = 12.4 Hz), 4.39 (1H, d, J = 11.6 Hz), 4.32 (1H, d, J = 7.6 Hz, H-1c), 4.23 (1H, d, J = 11.6 Hz), 4.14 (1H, d, J = 12.0 Hz), 4.02 (1H, d, J = 10.4 Hz), 3.95 (1H, d, J = 2.0 Hz), 3.88 (1H, d, J = 2.4 Hz), 3.88 - 3.83 (1H, m), 3.66 - 3.45 (9H, m), 3.41 - 3.34 (3H, m), 3.25 (3H, s, -OCH3), 3.20 (1H, dd, J = 8.4, 4.4 Hz), 1.97 (3H, s, -COCH3), 1.96 (3H, s, -COCH3). 13C NMR (100 MHz, CDC13) δ 170.1, 169.5, 156.2, 139.4, 138.9, 138.6, 138.2, 138.2, 138.1, 138.0, 136.6, 128.7, 128.6, 128.6, 128.4, 128.3, 128.3, 128.3, 128.1, 128.1, 128.1, 128.0, 127.9, 127.9, 127.9, 127.8, 127.8, 127.6, 127.4, 127.1, 117.8, 101.8, 101.7, 98.5, 80.5, 80.3, 78.7, 78.6, 75.0, 74.7, 73.8, 73.7, 73.5, 73.4, 72.9, 72.8, 72.0, 71.8, 71.3, 70.9, 68.7, 68.2, 67.6, 67.0, 55.1, 54.6, 21.2, 21.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 80 H 87 NO 19 Na 1388.5765; Found 1388.5812.

[0311] Example 62: Synthesis of oxime Ⅵ-17

[0312]

[0313] Following the reaction standard procedure C, white solid Ⅵ-17 (39 mg, 92%) was obtained. Rf = 0.24 (petroleum ether-ethyl acetate 3: 1). f = 0.24 (petroleum ether-ethyl acetate 3: 1). 1 H NMR (400 MHz, CDC13) δ 7.80 - 7.10 (23H, m, Ar-H), 5.76 (1H, d, J = 8.8, Hz, NH), 4.93 (1H, dd, J = 8.8, 8.4 Hz, H-2), 4.79 (1H, d, J = 11.6 Hz), 4.78 (1H, d, J = 11.2 Hz), 4.66 (1H, d, J = 11.6 Hz), 4.55 (2H, d, J = 11.6 Hz), 4.49 (1H, d, J = 12.0 Hz), 4.41 - 4.29 (4H, m), 4.36 (1H, d, J = 8.0 Hz, H-1), 4.23 (1H, t, J = 7.2 Hz), 3.74 - 3.61 (4H, m), 3.66 (3H, s, -OCH3), 3.40 (1H, m, H-5), 1.95 (3H, s, -COCH3), 1.18 (3H, d, J = 6.4 Hz).

[0314] Example 63: Synthesis of oxime Ⅵ-18

[0315]

[0316] Referring to the reaction standard operating procedure C, white foam Ⅵ-18 (34 mg, 83%) was obtained. Rf= 0.42 (petroleum ether-ethyl acetate 5:1). f = 0.42 (petroleum ether-ethyl acetate 5:1). 1 H NMR (600 MHz, CDC13) δ 7.33-7.25 (13H, m, Ar-H), 7.18 (2H, dd, J = 7.8, 1.8 Hz, Ar-H), 4.98 (1H, dd, J = 9.6, 7.8 Hz, H-2), 4.79 (1H, d, J = 11.4 Hz, -CH2Ph), 4.75 (1H, d, J = 10.8 Hz, -CH2Ph), 4.65 (1H, d, J = 11.4 Hz, -CH2Ph), 4.58 (1H, d, J = 12.0 Hz, -CH2Ph), 4.57 (1H, d, J = 10.8 Hz, -CH2Ph), 4.57-4.51 (1H, m), 4.51 (1H, d, J = 12.0 Hz, -CH2Ph), 4.46 (1H, d, J = 7.8 Hz, H-1), 3.89 (1H, d, J = 1.8 Hz), 3.72-3.68 (3H, m), 3.65 (3H, s), 3.63 (1H, t, J = 9.6 Hz), 3.41 (1H, ddd, J = 9.6, 4.2, 1.8 Hz, H-5), 2.36-2.31 (1H, m), 2.22-2.17 (1H, m), 2.06-1.99 (2H, m), 1.98 (3H, s, -COCH3), 1.96 (3H, s, -COCH3), 1.90-1.88 (1H, m), 1.84-1.81 (2H, m), 1.78-1.68 (3H, m), 1.64-1.57 (2H, m), 1.52-1.47 (3H, m), 1.42-1.38 (3H, m), 1.35-1.28 (2H, m), 1.25-1.11 (4H, m), 0.99 (1H, td, J = 11.4, 3.0 Hz), 0.91-0.87 (7H, m), 0.60 (3H, s, -CH3). 13C NMR (150MHz, CDCl3) δ175.0,170.9,169.7,138.5,138.5,138.2,128.6,128.6,128.6,128 .3,128.0,127.8,127.8,127.8,127.7,97.1,83.7,78.4,75.2,75.1,75.1,74.9,73.9,73 .5,72.7,69.2,55.4,51.6,49.4,42.7,41.5,39.3,39.2,35.5,35.3,35.3,34.9,32.7,31 .2,29.2,28.3,27.1,23.4,22.9,21.7,21.4,20.8,18.6,12.0.HRMS(ESI-TOF)m / z:[M+Na] + Calcd for C 56 H 74 O 11 Na 945.5123; Found 945.5113.

[0317] Example 64: Synthesis of Oxyglycoside VI-19

[0318]

[0319] According to the standard reaction procedure C, at -40 ° C, the receptor was added to trifluoromethanesulfonic anhydride to obtain colorless syrup VI-19 (39 mg, 95%). f =0.17 (petroleum ether-ethyl acetate 2:1). 1H NMR (400 MHz, CDC13) δ 7.35-7.26 (13H, m, Ar-H), 7.21-7.19 (2H, m, Ar-H), 7.14 (1H, s, Ar-H), 6.45 (1H, s, Ar-H), 6.33 (2H, Ar-H), 5.94 (2H, dd, J = 8.0, 1.2 Hz), 5.41 (1H, dd, J = 10.0, 8.0 Hz, H-2), 4.91 (1H, d, J = 11.6 Hz, -CH2Ph), 4.85 (1H, d, J = 10.0 Hz, -CH2Ph), 4.65 (1H, d, J = 12.0 Hz, -CH2Ph), 4.57 (1H, d, J = 12.0 Hz, -CH2Ph), 4.56-4.51 (2H, m), 4.48 (1H, d, J = 12.4 Hz, -CH2Ph), 4.40 (1H, d, J = 9.2 Hz, H-1), 4.39 (2H, br s, -CH2Ph), 4.03 (1H, t, J = 9.6 Hz), 3.91 (1H, d, J = 2.4 Hz, H-4), 3.76 (3H, s, -OCH3), 3.71 (6H, s, -OCH3), 3.61-3.46 (4H, m), 2.90-2.79 (1H, m), 2.74 (1H, dd, J = 14.4, 4.4 Hz), 1.98 (3H, s, -COCH3).

[0320] Example 65: Synthesis of oxime Ⅵ-20

[0321]

[0322] Referring to reaction standard procedure C, colorless syrup Ⅵ-20 (32.2 mg, 81%) was obtained. R f = 0.47 (petroleum ether-ethyl acetate 7:1). 1H NMR (600 MHz, CDC13) δ 7.42-7.39 (2H, m, Ar-H), 7.28-7.19 (17H, m, Ar-H), 5.15 (1H, br s), 5.05 (1H, t, J = 9.6 Hz), 4.88-4.82 (4H, m), 4.69 (1H, d, J = 12.0 Hz), 4.59-4.50 (5H, m), 4.09 (1H, d, J = 10.2 Hz), 3.87-3.84 (1H, m), 3.70-3.66 (2H, m), 3.58-3.56 (1H, m), 3.51 (1H, t, J = 9.0 Hz), 3.34-3.28 (1H, m), 2.44-2.38 (1H, m), 2.19-2.14 (1H, m), 1.71-1.66 (1H, m), 1.61-1.56 (1H, m), 1.44-1.39 (1H, m), 1.32-1.29 (1H, m), 1.24-1.21 (9H, m), 1.11 (6H, t, J = 6.6 Hz), 1.03 (3H, d, J = 6.0 Hz), 0.86 (3H, t, J = 7.2 Hz), 0.78 (3H, t, J = 7.2 Hz). 13 C NMR (10 MHz, CDC13) δ 176.9, 176.3, 175.8, 175.7, 169.8, 155.0, 150.5, 149.8, 143.1, 142.9, 138.6, 138.3, 136.4, 128.5, 128.5, 128.4, 128.1, 127.9, 127.8, 124.9, 123.8, 121.6, 111.0, 108.8, 107.8, 98.7, 79.9, 79.0, 78.2, 75.5, 74.3, 72.0, 68.7, 68.2, 39.5, 39.3, 39.3, 29.9, 27.4, 27.4, 27.3, 21.2, 18.1. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 57 H 70 O 15 Na 1017.4607; Found 1017.4639.

[0323] Example 66: Synthesis of Phenylsophoroside VI-21

[0324]

[0325] Following the reaction standard procedure A, colorless syrup VI-21 (31 mg, 97%) was obtained. Rf = 0.27 (petroleum ether-ethyl acetate 2: 1). f = 0.27 (petroleum ether-ethyl acetate 2: 1).1 H NMR (400 MHz, CDC13) δ 7.06 (2H, d, J = 9.2 Hz, Ar-H), 6.99 (2H, d, J = 9.2 Hz, Ar-H), 5.51 (1H, dd, J = 10.0, 3.6 Hz, H-3), 5.46 (1H, d, J = 1.6 Hz, H-1), 5.40 (1H, dd, J = 3.6, 2.0 Hz, H-2), 5.33 (1H, t, J = 10.0 Hz, H-4), 4.25 (1H, dd, J = 12.4, 5.6 Hz), 4.08 - 4.03 (2H, m), 2.25 (3H, s), 2.17 (3H, s), 2.03 (3H, s), 2.01 (3H, s), 2.00 (3H, s). 13 C NMR (100 MHz, CDC13) δ 170.7, 170.1, 170.1, 169.9, 169.8, 153.4, 146.1, 122.8, 117.4, 96.3, 69.5, 69.4, 69.0, 66.1, 62.3, 21.2, 21.0, 20.9, 20.8. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 22 H 26 O 12 Na 505.1316; Found 505.1337.

[0326] Example 67: Synthesis of ester glycoside VI-22

[0327]

[0328] Referring to the reaction standard operating procedure C, colorless syrup VI-22 (39 mg, 89%) was obtained. Rf = 0.44 (petroleum ether-ethyl acetate 5: 1). f = 0.44 (petroleum ether-ethyl acetate 5: 1). 1H NMR (400 MHz, CDC13) δ 7.36-7.26 (11H, m, Ar-H), 5.98 (1H, d, J = 1.6 Hz, H-1), 5.28-5.25 (2H, m), 4.91 (1H, d, J = 11.2 Hz), 4.70 (1H, d, J = 11.2 Hz), 4.62 (1H, d, J = 10.8 Hz), 4.53-4.45 (2H, m), 3.84 (1H, dd, J = 9.2, 3.2 Hz), 3.81-3.74 (1H, m), 3.46 (1H, t, J = 9.6 Hz), 2.81 (1H, dd, J = 13.6, 4.0 Hz), 2.15 (3H, s), 2.02 (3H, s), 1.95 (1H, td, J = 13.6, 4.0 Hz), 1.83 (2H, dd, J = 8.8, 3.2 Hz), 1.27 (3H, d, J = 6.0 Hz), 1.11 (3H, s), 0.91 (3H, s), 0.89 (3H, s), 0.87 (3H, s), 0.85 (3H, s), 0.83 (3H, s), 0.76 (3H, s). 13 C NMR (100 MHz, CDC13) δ 175.1, 171.2, 170.2, 143.4, 138.5, 137.8, 128.7, 128.6, 128.3, 128.2, 128.1, 128.0, 123.2, 90.9, 81.1, 79.7, 77.9, 75.7, 72.1, 70.4, 68.3, 55.6, 47.7, 47.3, 45.8 42.0, 41.7, 39.6, 38.4, 37.9, 37.1, 33.9, 33.2, 33.1, 32.6, 30.9, 28.3, 27.7, 26.0, 23.8, 23.7, 23.6, 23.1, 21.5, 21.2, 18.4, 18.2, 17.4, 16.9, 15.6. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 54 H 74 O9Na 889.5225; Found 889.5221.

[0329] Example 68: Synthesis of pyrimidine nucleoside VI-23

[0330]

[0331] Pre-treatment of acceptor with silyl ether: Weigh acceptor V-21 (26 mg, 0.23 mmol) and add acetonitrile (0.6 mL) and N, O-bis(trimethylsilyl)trifluoroacetamide (BSTFA, 123 μL) under argon protection. Stir the mixture at room temperature for 0.5 h to give silyl ether of acceptor V-21'.

[0332] Refer to reaction standard procedure B, donor IV-15 (35 mg, 1.0 eq), reagent I-02 (29 mg, 1.2 eq), triflic anhydride (16 μL, 1.2 eq). After 10 min of anhydride addition, add the acetonitrile solution of silyl ether of acceptor V-21' above. White solid VI-23 (33.0 mg, 97%) is obtained. Rf= 0.43 (petroleum ether-ethyl acetate 1:3). f 1 HNMR (400 MHz, CDC13) δ 8.78 (1H, br s, NH), 8.10-8.08 (2H, m, Ar-H), 7.96-7.86 (7H, m, Ar-H), 7.62-7.46 (9H, m, Ar-H), 7.35 (4H, t, J = 8.0 Hz, Ar-H), 6.44 (1H, d, J = 4.8 Hz, H-1'), 5.90 (1H, t, J = 5.6 Hz), 5.83 (1H, t, J = 5.2 Hz), 4.85 (1H, dd, J = 12.0, 2.8 Hz), 4.79-4.76 (1H, m), 4.71 (1H, dd, J = 12.4, 4.0 Hz).

[0333] Example 69: Synthesis of pyrimidine nucleoside VI-24

[0334]

[0335] Pre-treatment of acceptor with silyl ether: Weigh acceptor V-21 (26 mg, 0.23 mmol) and add acetonitrile (0.6 mL) and N, O-bis(trimethylsilyl)trifluoroacetamide (BSTFA, 123 μL) under argon protection. Stir the mixture at room temperature for 0.5 h to give silyl ether of acceptor V-21'.

[0336] Refer to reaction standard procedure B, donor IV-15 (35 mg, 1.0 eq), reagent I-02 (29 mg, 1.2 eq), triflic anhydride (16 μL, 1.2 eq). After 10 min of anhydride addition, add the acetonitrile solution of silyl ether of acceptor V-21' above. White solid VI-23 (33.0 mg, 97%) is obtained. Rf= 0.43 (petroleum ether-ethyl acetate 1:3). f 1 ​​HNMR (400 MHz, CDC13) δ 8.78 (1H, br s, NH), 8.10-8.08 (2H, m, Ar-H), 7.96-7.86 (7H, m, Ar-H), 7.62-7.46 (9H, m, Ar-H), 7.35 (4H, t, J = 8.0 Hz, Ar-H), 6.44 (1H, d, J = 4.8 Hz, H-1'), 5.90 (1H, t, J = 5.6 Hz), 5.83 (1H, t, J = 5.2 Hz), 4.85 (1H, dd, J = 12.0, 2.8 Hz), 4.79-4.76 (1H, m), 4.71 (1H, dd, J = 12.4, 4.0 Hz).

[0337] Example 70: Synthesis of Pyrimidine Nucleoside VI-25

[0338]

[0339] Pre-treatment of acceptor with silylation: Weigh out acceptor V-23 (37 mg, 0.28 mmol), and add acetonitrile (0.7 mL) and N, O-bis(trimethylsilyl)trifluoroacetamide (BSTFA, 149 μL) successively under argon protection, and react at room temperature for 0.5 h to obtain silylated acceptor V-23'.

[0340] Refer to reaction standard procedure B, donor IV-28 (30 mg, 1.0 eq), reagent I-02 (34 mg, 1.2 eq), triflic anhydride (15 μL, 1.2 eq). After 10 min of anhydride addition, add the acetonitrile solution of silylated acceptor V-23' above. Obtain colorless syrup VI-25 (30 mg, 98%). 1 H NMR (600 MHz, CDC13) δ 9.61 (br s, 1H), 7.36 (d, J = 5.4 Hz, 1H), 5.94 (d, J = 4.8 Hz, 1H), 5.29 (t, J = 5.4 Hz, 1H), 5.01 (t, J = 5.4 Hz, 1H), 4.24-4.19 (m, 1H), 2.11 (s, 3H), 2.09 (s, 3H), 1.45 (d, J = 6.6 Hz, 3H).

[0341] Example 71: Synthesis of Purine Nucleoside VI-26

[0342]

[0343] Refer to reaction standard procedure C, react at 30 °C for 24 h. Obtain colorless syrup VI-26 (32 mg, 94%). 1HNMR (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-l'), 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).

[0344] Example 72: Synthesis of carboside VI-27

[0345]

[0346] Referring to reaction standard procedure B, donor IV-19 (30 mg, 1.0 eq), reagent I-09 (21 mg, 1.2 eq), 2,6-di-tert-butyl-4-methylpyridine (13 mg, 1.2 eq), triflic anhydride (11 μL, 1.2 eq). After 10 min of anhydride addition, enol silyl ether acceptor V-25 was added. White foamy solid VI-27 (25 mg, 85%) was obtained. Rf = 0.28 (petroleum ether-ethyl acetate 7:1). f 1 ​H NMR (600 MHz, CDC13) δ 7.81 (2H, dd, J = 8.4, 1.2 Hz, Ar-H), 7.56 (1H, tt, J = 7.2, 1.2 Hz, Ar-H), 7.52 (2H, dd, J = 7.8, 1.2 Hz, Ar-H), 7.43 (4H, t, J = 7.8 Hz, Ar-H), 7.40-7.34 (5H, m, Ar-H), 7.31-7.26 (3H, m, Ar-H), 7.17-7.14 (2H, m, Ar-H), 7.12-7.09 (1H, m, Ar-H), 5.65 (1H, s, -CHPh), 5.02 (1H, d, J = 12.0 Hz, -CH2Ph), 4.95 (1H, d, J = 12.6 Hz, -CH2Ph), 4.80 (1H, d, J = 12.0 Hz, -CH2Ph), 4.61 (1H, d, J = 11.4 Hz, -CH2Ph), 4.26 (1H, dd, J = 10.8, 2.4 Hz, H-6a), 4.25 (1H, dd, J = 10.2, 1.2 Hz, H-6b), 4.16-4.14 (1H, m, H-1), 4.05 (1H, dd, J = 3.0, 1.2 Hz, H-2), 3.88 (1H, dd, J = 10.2, 3.0 Hz, H-3), 3.82 (1H, t, J = 10.2 Hz, H-4), 3.47 (1H, td, J = 10.2, 4.8 Hz), 3.24 (1H, dd, J = 18.0, 4.8 Hz), 3.13 (1H, dd, J = 18.0, 7.8 Hz). 13 CNMR (150 MHz, CDC13) δ 197.5, 138.8, 138.2, 137.9, 136.7, 133.5, 129.0, 128.7, 128.6, 128.5, 128.4, 128.3, 128.0, 127.8, 127.8, 126.3, 101.6, 80.7, 79.6, 76.2, 75.8, 75.3, 73.5, 72.1, 68.8, 39.8. HRMS (ESI-TOF) m / z: [M + Na] + Calcd for C 35 H 34 O6Na 573.2248; Found 505.2233.

[0347] The above examples are merely examples, for example, the base used in the disulfide construction step E can also use other kinds of bases (such as sodium hydroxide, potassium hydroxide, sodium carbonate, potassium phosphate) in addition to potassium carbonate, and the amount of base can be preferably controlled to a molar ratio of 0.5-1.0 of the compound represented by the structural general formula (III) to the base.

[0348] It is readily understood by those skilled in the art that the foregoing description is only a preferred embodiment of the application and is not intended to limit the application thereto. Any modifications, equivalents and improvements, etc., made during the practice of the application, within the spirit and principle of the application, shall be included within the protection scope of the application.

Claims

1. An unsymmetrical disulfide compound containing a sulfoxide group, characterized in that, has a structure as shown in structural general formula (I): wherein S is a sulfur atom, and O is an oxygen atom; R 1 selected from the group consisting of methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and R 2 is selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2,3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, and 4-bromophenyl; X is selected from and (CH2)2.

2. The asymmetric disulfide compound containing a sulfoxide group according to claim 1, wherein, The structural formula of the asymmetric disulfide compound containing a sulfoxide group is specifically any one of formula I-01 to formula I-31:

3. The method for producing an unsymmetrical disulfide compound containing a sulfoxide group according to claim 1 or 2, wherein The preparation method is to use a compound containing a sulfide structure and having a leaving group as shown in structural general formula (II) as a starting material, wherein S is a sulfur atom, and O is an oxygen atom; and LG is a leaving group. R 1 selected from the group consisting of methyl, ethyl, isopropyl, phenyl, 4-methylphenyl and X is selected from and (CH2)2; The preparation method specifically comprises the following steps: (S1) oxidizing the compound shown in structural general formula (II) by an oxidizing agent to obtain a compound containing a sulfoxide group shown in structural general formula (III); (S2) reacting the compound of structural formula (III) with sodium thiosulfate pentahydrate in an aqueous solution until the reaction is complete, wherein the molar ratio of the compound of structural formula (III) to sodium thiosulfate pentahydrate is 0.2 to 1.0; and then sequentially adding a hydrophobic solvent, R 2 SH and a base, or sequentially adding a hydrophobic solvent and R 2 SM to produce an unsymmetrical disulfide compound containing a sulfoxide group of structural formula (I). The reaction route is as shown below: wherein R 2 M in SM is an alkali metal element; R 2 SH and R 2 R in SM 2 is selected from the group consisting of methyl, ethyl, benzyl, 4-methoxybenzyl, phenyl, 4-methylphenyl, 4-methoxyphenyl, 2-methoxyphenyl, 3-methoxyphenyl, 2,3-dimethoxyphenyl, 4-nitrophenyl, 4-trifluoromethylphenyl, 4-fluorophenyl, 4-chlorophenyl, and 4-bromophenyl.

4. The preparation method according to claim 3, wherein In the step (S1), the oxidizing agent is meta-chloroperoxybenzoic acid (m-CPBA) or Eosin Y, or a mixture of hydrogen peroxide (H2O2) and an acid; when the oxidizing agent is the mixture of hydrogen peroxide (H2O2) and an acid, the acid is any one of acetic acid or diphenyl phosphate; In the step (S2), the base is any one of sodium hydroxide, potassium hydroxide, potassium carbonate, sodium carbonate, or potassium phosphate, and is preferably potassium carbonate; The hydrophobic solvent is any one of dichloromethane, dichloroethane, ethyl acetate, toluene, or n-butanol, and is preferably dichloromethane; The compound of structural general formula (III) and R 2 The molar ratio of SH is 0.2-1.0, and the molar ratio of the compound of structural general formula (III) and base is 0.5-1.0; or, the molar ratio of the compound of structural general formula (III) and R 2 The molar ratio of SM is 0.2-1.

0.

5. The preparation method according to claim 3, wherein: In the structural general formula (II), the LG is preferably a bromine atom, a chlorine atom, or a p-toluenesulfonyl group; M is preferably sodium or potassium.

6. Use of the asymmetric disulfide compound containing a sulfoxide group according to claim 1 or 2 as an activating agent in a glycosylation reaction.

7. The use according to claim 6, characterized in that, The application is specifically that the asymmetric disulfide compound containing a sulfoxide group participates in the activation of a glycosyl donor to realize the connection between glycosyl units or the connection between a glycosyl unit and a non-sugar unit.

8. The use according to claim 6, characterized in that, The application is specifically that, in an organic solvent, a combination of an activating agent as shown in structural general formula (I) and triflic anhydride is used as a promoter to make a glycosyl donor as shown in structural general formula (IV) and an acceptor as shown in formula (V) undergo a glycosylation reaction to obtain a glycosylation product as shown in formula (VI); the reaction equation is as follows: In the sugar donor of structural formula (IV), Gly is a sugar group in which the hydroxyl and / or amino groups on the sugar ring are protected by a protecting group; Z is a sulfur or selenium atom; R 3 selected from substituted or unsubstituted alkyl, substituted or unsubstituted aryl; The acceptor as shown in formula (V) is selected from a sugar nucleophile in which a hydroxyl group and / or an amino group on a sugar ring is protected by a protecting group, or an alcohol, a phenol, a carboxylic acid, a pyrimidine, a purine, or an enol silyl ether nucleophile containing one or more nucleophilic groups.

9. The use according to claim 6, characterized in that, Gly or the acceptor as shown in formula (V), the sugar is independently selected from any one of D-glucose, D-galactose, D-mannose, L-rhamnose, D-xylose, D-quinovose, D-fucose, L-fucose, 2-deoxy-L-fucose, D-ribose, 6-deoxy-D-ribose, sialic acid, D-glucuronic acid, 2-amino-2-deoxy-D-glucose, and 3-aminopolysaccharide. Gly or the acceptor represented by formula (V), the protecting group is independently selected from any one of acetyl (Ac), benzoyl (Bz), benzyl (Bn), tert-butyldimethylsilyl (TBS), benzaldehyde acetal, carbonate, nitrocarbonate, propionyl ketals, benzyloxycarbonyl (Cbz), p-methoxyphenyl (MP), S-2-methylbutyryl (Mba), p-nitrobenzenesulfonyl (Ns); R 3 selected from substituted or unsubstituted methyl, substituted or unsubstituted ethyl, substituted or unsubstituted propyl, substituted or unsubstituted 1-adamantyl, substituted or unsubstituted phenyl; wherein the substituents are one or more, independently selected from methyl, ethyl, methoxy, phenyl; The organic solvent is one or more of halogenated hydrocarbon solvents, aromatic hydrocarbon solvents, and nitrile solvents; The molar ratio of the asymmetric disulfide compound containing a sulfoxide group represented by the general structural formula (I) to the glycosyl donor represented by the general structural formula (IV) is 0.5-1.2; The molar ratio of triflic anhydride to the glycosyl donor represented by the general structural formula (IV) is 0.5-1.2; The reaction temperature of the glycosylation reaction is in the range of -78-30℃.

10. The use according to claim 6, characterized in that, The glycosyl donor represented by the general structural formula (IV) is any one of the compounds represented by the structural formula IV-01 to the structural formula IV-29: The acceptor represented by formula (V) is a sugar nucleophile in which the hydroxyl and / or amino groups on the sugar ring are partially protected by a protecting group, and is specifically any one of the compounds represented by the structural formula V-01 to the structural formula V-13: Alternatively, the acceptor represented by formula (V) is an alcohol nucleophile, and is specifically any one of the compounds represented by the structural formula V-14 to the structural formula V-18: Alternatively, the acceptor represented by formula (V) is a phenol or carboxylic acid nucleophile, and is specifically the compound represented by the structural formula V-19 or the structural formula V-20: Alternatively, the acceptor represented by formula (V) is a pyrimidine or purine nucleophile, and is specifically any one of the compounds represented by the structural formula V-21 to the structural formula V-24: Alternatively, the acceptor represented by formula (V) is an enol silyl ether nucleophile, and is specifically the compound represented by the structural formula V-25:

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