A selenoglycosyl donor, a selenoglycoside compound and a preparation method thereof

Abstract

The present invention provides a selenoglycosyl donor, a selenoglycoside compound, and a preparation method thereof. The selenoglycosyl donor provided by the present invention has a novel structure and a simple preparation method. The present invention also uses the selenoglycosyl donor as a raw material and utilizes an inexpensive copper-catalyzed reaction to prepare a selenoglycoside compound with a special β-configuration. This preparation method is simple, has mild reaction conditions, and a high yield, and has excellent application prospects.

Description

Technical Field

[0001] The present invention relates to the technical field of medicinal chemistry, and in particular to a selenoglycoside donor, a selenoglycoside compound and a preparation method thereof. Background Art

[0002] Selenoglucosides are a subset of selenium-containing compounds that are known to have a variety of useful biological activities, specifically their anti-metastatic, immunostimulatory and anti-tumor activities. At the same time, selenoglucosides can also be used as probes to study carbohydrate-protein interactions. In addition, selenoglucosides have unique reactivity as glycosyl donors. Under photo and electrochemical conditions, the C-Se bond easily loses electrons, thereby generating cations or free radical-cation intermediates, which causes the carbon-selenium bond to break and then undergo glycosylation. There are currently three main methods for synthesizing selenoglucosides, such as Figure 1 As shown. The first type is prepared by coupling a sugar-based electrophilic reagent with a nucleophilic selenium reagent (J.Carbohydr.Chem.1996,15,183;Carbohydr.Res.1990,206,361). The disadvantage of this method is that the nucleophilic selenium reagent cannot be directly obtained and requires multi-step preparation. In addition, the selenol used is toxic, has poor stability and has a bad odor. The second type is to prepare various types of selenoglycosides by in situ generating isomer selenate anions from β-p-methylbenzoylselenoglycoside and reacting them with various electrophilic reagents (Org.Lett.2005,7,4653). Although this method has good stereoselectivity and a wide substrate range, it can synthesize alkyl, aryl, selenoglycosyl amino acids and selenodisaccharides and other types of selenoglycosides, but its compatibility with heterocyclic substrates is not high. The third method is to react a sugar-based nucleophilic reagent with a diselenide. Coupling of glycosylstannanes with symmetrical diselenides under copper catalysts (Angew. Chem. Int. Ed. 2018, 57, 7091) requires a high reaction temperature (110°C) and the use of toxic alkyltin species in multiple steps to prepare the raw material 1-tin-based sugars, resulting in a cumbersome reaction process. Therefore, developing novel, highly active selenoglycoside donors for the synthesis of selenoglycosides has great application value. Summary of the Invention

[0003] Based on the above reasons, the present invention provides a selenoglycoside donor, a selenoglycoside compound and a preparation method thereof.

[0004] To achieve the above object, the present invention adopts the following technical solutions:

[0005] A selenoglycosyl donor, the structure of which is shown in Formula I:

[0006]

[0007] Among them, ring A is selected from R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M1OH, M1OAc, M1OBn, M1OSi, M1 is selected from 0-3 methylene groups; Ar is selected from unsubstituted or substituted benzene ring, naphthalene ring, indole, quinoline, etc.

[0008] Furthermore, the structure of the selenoglycosyl donor is shown in Formula III:

[0009]

[0010] Among them, R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, M1OH, M1OAc,

[0011] M1OBn, M1OSi, M1 is selected from 0-3 methylene groups; Ar is selected from unsubstituted or substituted benzene ring, naphthalene ring, indole, quinoline and the like.

[0012] Furthermore, the structure of the selenoglycosyl donor is selected from:

[0013]

[0014] Furthermore, the structure of the selenoglycosyl donor is selected from:

[0015]

[0016] in express or a mixture of the two in any proportion.

[0017] A selenoglycoside compound, the structure of which is shown in Formula II:

[0018]

[0019] Among them, R 5 is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted alkenyl;

[0020] Ring A is selected from R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6Alkyl, M1OH, M1OAc, M1OBn, M1OSi, M1 is selected from 0-3 methylene groups.

[0021] Furthermore, the structure of the selenoglycoside compound is shown in Formula IV:

[0022]

[0023]

[0024] Wherein: R5 is selected from substituted or unsubstituted aryl, substituted or unsubstituted nitrogen heteroaryl, oxygen heteroaryl ring, sulfur heteroaryl ring, substituted or unsubstituted alkenyl.

[0025] Furthermore, the structure of the selenoglycoside compound is selected from:

[0026]

[0027] Furthermore, the structure of the selenoglycoside compound is selected from:

[0028]

[0029] Furthermore, the preparation method of the selenoglycosyl donor comprises the following steps:

[0030] (1) reacting raw material Y1 with acetic anhydride to obtain intermediate product Y2;

[0031] (2) intermediate product Y2 reacts with hydrobromic acid to obtain compound Y3;

[0032] (3) reacting the raw material selenium powder with sodium borohydride to obtain compound Z1;

[0033] (4) Compound Z1 reacts with potassium hydroxide, and then compound Y3 is added to obtain compound Y4;

[0034] (5) Compound Y4 reacts with piperazine to obtain compound Y5;

[0035] (6) Compound Y5 reacts with thionyl chloride and sodium phenylsulfinate to obtain a selenoglycosyl donor;

[0036] Among them, the structure of raw material Y1 is The structure of intermediate Y2 is The structure of compound Y3 is The structure of compound Z1 is The structure of compound Y4 is The structure of compound Y5 is

[0037] R 1 、R 2 、R 3 、R4 Each independently selected from H, C 1-6 Alkyl, M1OH, M1OAc, M1OBn, M1OSi, M1 is selected from 0-3 methylene groups.

[0038] Furthermore, in step (1), the reaction is carried out under the action of sodium acetate; the reaction temperature is 50-150°C, preferably 70-110°C; the reaction solvent is acetic anhydride;

[0039] Furthermore, in step (2), the molar ratio of hydrogen bromide to Y2 is 10:1, preferably 5:1 to 3:1; the reaction temperature is 10-70°C, preferably 20-40°C; the reaction solvent is a chlorinated alkane, preferably dichloroethane, dichloromethane, or chloroform;

[0040] Furthermore, in step (3), the molar ratio of selenium powder to sodium borohydride is 0.5:5, preferably 0.5:1 to 0.5:3; the reaction is carried out under the action of elemental iodine and potassium iodide; the reaction temperature is -20 to 60°C, preferably -10 to 30°C; the reaction solvent is an alcohol solvent, preferably methanol, ethanol, or isopropanol;

[0041] Furthermore, in step (4), the molar ratio of compound Z1 to potassium hydroxide and compound Y3 is 10:10:1 to 1:1:1, preferably 5:5:1 to 1:1:1, the reaction temperature before adding Y3 is 10 to 70°C, preferably 20 to 40°C, and the reaction solvent is an aromatic hydrocarbon, preferably toluene or xylene; the reaction after adding Y3 is carried out under the action of sodium carbonate and tetrabutylammonium hydrogen sulfate, and the reaction temperature after adding Y3 is 10 to 70°C, preferably 20 to 40°C; the reaction solvent is ethyl acetate;

[0042] Furthermore, in step (5), the molar ratio of compound Y4 to piperazine is 5:1 to 1:5, preferably 3:1 to 1:3; the reaction temperature is 10 to 70°C, preferably 20 to 40°C; the reaction solvent is a highly polar solvent, preferably DMSO, DMF, DMA, or NMP;

[0043] Furthermore, in step (6), the molar ratio of compound Y5 to sodium phenylsulfinate is 3:1 to 1:20, preferably 1:1 to 1:10; the reaction is carried out under the action of dichloride; the reaction temperature is 10 to 70°C, preferably 20 to 40°C; and the reaction solvent is acetonitrile.

[0044] Furthermore, the preparation method of the selenoglycoside compound comprises: reacting the selenoglycosyl donor prepared above with a glycosyl acceptor to obtain a selenoglycoside compound;

[0045] Wherein, the structure of the glycosyl acceptor is (HO)2B-R 5 or its derivative boron ester, potassium fluoroborate, etc., R 5is selected from substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, and substituted or unsubstituted alkenyl.

[0046] Furthermore, the molar ratio of the glycosyl donor to the glycosyl acceptor is 5:1 to 1:5, preferably 2:1 to 1:2; the reaction is carried out under a nitrogen atmosphere; the reaction temperature is 0 to 100°C, preferably room temperature to 50°C; the reaction time is 12 to 48 hours, preferably 12 hours; the reaction is carried out under the action of a copper catalyst, the catalyst being selected from CuTc, CuCl, CuBr, CuOAc, Cu2S, CuBr2, CuF2, preferably CuTc, CuBr, more preferably CuTc; the reaction solvent is selected from THF, DMF, DMSO, CH3OH, 1,2-DCE, toluene, preferably THF, 1,2-DCE, more preferably THF.

[0047] The advantages of the present invention are:

[0048] 1. Single configuration, no stereoselectivity issues. Conventional methods often produce a mixture of α and β isomers during the attack of the selenium nucleophile on the glycosyl bromide, with a poor α:β ratio, resulting in a difficult-to-separate product. The present invention eliminates the need for stereocenter construction, resulting in a single product configuration.

[0049] 2. Wide application. Traditional selenoglycoside synthesis strategies mostly yield single product structures. However, phenylsulfone selenoglycosides and arylboronic acids can be used to synthesize a range of aryl and heteroaryl selenoglycosides, increasing the diversity of this class of compounds. This glycosyl donor can also participate in a variety of reaction types, further enriching the selenoglycoside molecular library.

[0050] 3. Achieve post-modification of bioactive molecules. Traditional methods often use aromatic groups derived from corresponding selenoethers, but the variety of selenoethers is limited, and selenoethers with biologically active structures are even rarer. Therefore, it is difficult to obtain selenoglycosides with biologically active structures using traditional methods. The present invention is expected to facilitate the synthesis of molecules with biologically active structures using phenylsulfone selenoglycosides. BRIEF DESCRIPTION OF THE DRAWINGS

[0051] Figure 1 This paper provides an overview of the synthesis methods of selenoglycoside compounds. DETAILED DESCRIPTION

[0052] A method for preparing a selenoglycosyl donor comprises the following steps:

[0053] (1) In a solvent, a saccharide raw material and a selenoether are reacted under the action of a base to obtain an intermediate; the reaction flow is as follows:

[0054]

[0055] (2) The intermediate undergoes a self-coupling reaction under the action of a base to obtain a glycosyl selenoether; the reaction flow is as follows:

[0056]

[0057] (3) In an organic solvent, the glycosyl selenoether is converted under the action of a chlorination reagent and reacted with sodium phenylsulfinate to produce the desired selenoglycosyl donor. The reaction flow is as follows:

[0058]

[0059] in, Selected from R 1 、R 2 、R 3 、R 4 Each independently selected from H, C 1-6 Alkyl, (CH2) n OBn, (CH2) n OTMS, (CH2) n OTBS, (CH2) n OMe, (CH2) n NHAc, (CH2) n OAc, n is an integer selected from 0-3; LG is a leaving group selected from halogen, trichloroacetimide or p-toluenesulfonate;

[0060] Furthermore, the molar ratio of the glycosylated raw material to the selenoether used in step (1) is 1:2; the amount ratio of the glycosylated raw material to the solvent ranges from 1 g / 1 mL to 1 g / 50 mL; and the molar ratio of the base to the glycosylated raw material is from 1:1 to 5:1.

[0061] The solvent is any one of tetrahydrofuran, toluene, N,N-dimethylformamide, N,N-dimethylacetamide, dimethyl sulfoxide, acetone, and ethyl acetate.

[0062] The base is any one of sodium carbonate, sodium phosphate, potassium phosphate, sodium acetate, potassium acetate, and sodium alkoxide.

[0063] Furthermore, the ratio of the base to the intermediate used in step (2) is 1:1-10:1; the ratio of the intermediate to the solvent is in the range of 1 g / 1 mL-1 g / 50 mL.

[0064] Wherein, the base is any one of triethylamine, diisopropylamine, dimethylethanolamine, piperazine, and benzenesulfonamide.

[0065] The solvent is any one of toluene, N,N-dimethylformamide, N,N-dimethylacetamide and dimethyl sulfoxide.

[0066] Furthermore, the molar ratio of the chlorination reagent used in step (3) to the glycosyl selenoether is 1:1-10:1; the molar ratio of the sodium p-toluenesulfinate to the glycosyl selenoether used is 1:1-10:1; and the amount ratio of the glycosyl selenoether to the solvent ranges from 1 g / 1 mL to 1 g / 50 mL.

[0067] The organic solvent is one or more of a nitrile solvent and an amide solvent. Furthermore, the nitrile solvent is one or more of acetonitrile, propionitrile, and benzonitrile; and the amide solvent can be N,N-dimethylformamide or N,N-dimethylacetamide.

[0068] Furthermore, the temperature of the reaction involved in steps (1), (2) and (3) is 50°C-100°C, and the time is 1 minute to 48 hours; wherein, the preferred temperature of the reaction in step (1) is 25°C, and the preferred time is 1-24 hours, and the preferred temperature of the reaction involved in step (2) is 25°C, and the preferred time is 1-24 hours.

[0069] To make the above features and advantages of the present invention more clearly understood, the following embodiments are given for detailed description. The methods of the present invention are all conventional methods in the art unless otherwise specified.

[0070] Example 1. Preparation of p-methylbenzoylselenoglycoside

[0071] 1. A selenoether (compound b1, 4 g, 0.01 mol) (compound b1 was synthesized according to reaction step 1.2.3 of Scheme 2 in the literature (Org. Lett. 2005, 7, 4653)) was dissolved in toluene (23.52 ml). Potassium hydroxide / methanol solution (0.566 g dissolved in 10 ml) was added. After stirring for 10 minutes, the solvent was removed by rotary evaporation and washed with petroleum ether to obtain compound b2, the reaction formula of which is as follows:

[0072]

[0073] 2. Dissolve 2,3,4,6-tetra-O-acetyl-D-pyranose glucopyranose bromide (Compound a2, CAS: 572-09-8, 3.64 g, 0.009 mol) in ethyl acetate (182 ml), add Compound b2, tetrabutylammonium hydrogen sulfate (6 g, 0.018 mol), and aqueous sodium carbonate solution (3.85 g dissolved in 36.4 ml). Stir at room temperature for three hours and then wash with petroleum ether to obtain the target product p-methylbenzoylselenoside a3 (3.7 g, 78%).

[0074]

[0075] Its NMR data are as follows:1 HNMR (400MHz, CDCl3) δ7.75(d,J=7.9Hz,2H),7.27(d,J=6.6Hz,H),5.51(dd,J=7.5,2.9Hz,1H),5.37–5.29(m,2H),5.17–5.19(m ,1H),4.30(dd,J=12.4,4.5Hz,1H),4.12(dd,J=12.5,2.0Hz,1H),3.95–3.79(m,1H),2.41(s,3H),2.03(q,J=22.2,11.7Hz,12H).

[0076] Example 2. Preparation of Tetraacetyl Glucose Selenide

[0077] The p-methylbenzoylselenoside a3 (2.3 g, 0.004 mol) obtained in Example 1 was dissolved in N,N-dimethylformamide (49 ml), and piperazine (0.44 g, 0.005 mol) was added. After stirring at room temperature for 10 minutes, the mixture was washed with petroleum ether to obtain the target product tetraacetyl glucose selenoether a4 (1.38 g, 80%).

[0078]

[0079] Its NMR data are as follows: 1 H-NMR (500MHz, CDCl3) δ5.46 (d, J = 3.4Hz, 2H), 5.37 (dd, J = 9.7, 10.3Hz, 2H), 5.08 (d d,2H),4.93(d,J=10.3Hz,2H),4.12(dd,2H),4.04(m,2H),2.18-1.99(4s,24H,8Ac); 13 C-NMR (125MHz, CDCl3) δ170.2,170.1,170.0,169.5,81.2,75.5,71.5,69.4,67.1,60.8,20.9,20.6,20.6,20.5

[0080] Example 3.1 - Preparation of p-Toluenesulfonylselenotetraacetylglucose

[0081] Tetraacetyl glucose selenoether a4 (0.261 g, 0.0003 mol) obtained in Example 2 was dissolved in anhydrous acetonitrile (6.4 ml), and sodium p-toluenesulfinate (0.585 g, 0.003 mol) and thionyl chloride (60 μl, 0.0008 mol) were added. The mixture was stirred at room temperature for 12 hours and then filtered. The solvent was removed by rotary evaporation of the filtrate, and the target product 1-p-toluenesulfonylselenotetraacetyl glucose a5 (0.157 g, 44%) was obtained by column chromatography (petroleum ether:ethyl acetate volume ratio 1:1).

[0082]

[0083] Its NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.79(d,J=8.2Hz,2H),7.32(d,J=8.1Hz,2H),5.54(d,J=10.5Hz,1H),5.29(t,J=9.3Hz,1H),5.08(t,J= 9.8Hz, 2H), 4.17 (dd, J=12.5, 4.5Hz, 1H), 4.02 (dd, J=12.5, 2.3Hz, 1H), 3.81–3.74 (m, 1H), 2.45 (s, 3H), 2.08–1.96 (m, 12H).

[0084] Application Example 1. Preparation of p-nitrophenyl tetraacetyl glucose selenoglycoside product

[0085] 1-p-Toluenesulfonylselenotetraacetylglucose a5 (0.056 g, 0.0001 mol) obtained in Example 3 was dissolved in anhydrous ethyl acetate (2 ml), and p-nitrophenylboric acid (0.025 g, 0.00015 mol), cuprous oxide (I) (0.0028 g, 0.00002 mol), 2,2-bipyridine (0.0031 g, 0.00002 mol), and sodium acetate (0.00082 g, 0.0001 mol) were added. The mixture was stirred at room temperature for 12 h to obtain the product, as shown in the following reaction formula. The total yield was 94%, and the α / β ratio was less than 1:20.

[0086]

[0087] Its NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ8.14–8.08(m,2H),7.73(d,J=8.6Hz,2H),5.22(ddd,J=9.3,6.0,2.9Hz,1H),5.08–4.96 (m,3H),4.20(dd,J=7.5,3.7Hz,2H),3.80–3.71(m,1H),2.08(s,3H),2.05(s,3H),2.01(s,3H),1.97(s,3H). 13 C NMR (101MHz, CDCl3) δ170.5,170.1,169.4,169.4,147.8,136.8,134.5,123.8,80.6,77.2,73.6,70.5,68.1,62.1,20.8,20.8,20.6.

[0088] Application Example 2. Preparation of Benzofuranyltetraacetylglucose Selenoglucoside Product

[0089] 1-toluenesulfonylselenotetraacetylglucose a5 (0.056 g, 0.0001 mol) obtained in Example 3 was dissolved in anhydrous tetrahydrofuran (2 ml), and benzofuran-2-boric acid (0.025 g, 0.00015 mol), cuprous oxide (I) (0.0028 g, 0.00002 mol), 2,2-bipyridine (0.0031 g, 0.00002 mol), and sodium acetate (0.00082 g, 0.0001 mol) were added. The mixture was stirred at room temperature for 12 h to obtain the product, which has the following reaction formula. The total yield is 96%, and the α / β ratio is less than 1:20.

[0090]

[0091] Its NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.58–7.52(m,1H),7.48(d,J=8.2Hz,1H),7.34–7.19(m,2H),7.07(s,1H),5.19(t,J=9.2Hz,1H) ,5.14–4.92(m,3H),4.15(qd,J=12.4,3.6Hz,2H),3.69–3.65(m,1H),2.09(s,3H),1.99(d,J=4.5Hz,6H),1.93(s,3H). 13 CNMR (101 MHz, CDCl3) δ 170.6, 170.2, 169.5, 169.4, 157.6, 140.5, 128.5, 125.2, 123.2, 120.9, 117.4, 111.4, 80.5, 77.2, 73.8, 71.1, 68.0, 62.0, 20.9, 20.7, 20.6. Application Example 3. Preparation of benzothienyl tetraacetyl glucose selenoglycoside product

[0092] 1-toluenesulfonylselenotetraacetylglucose a5 (0.056 g, 0.0001 mol) obtained in Example 3 was dissolved in anhydrous tetrahydrofuran (2 ml), and benzothiophene-2-boric acid (0.027 g, 0.00015 mol), cuprous oxide (I) (0.0028 g, 0.00002 mol), 2,2-bipyridine (0.0031 g, 0.00002 mol), and sodium acetate (0.00082 g, 0.0001 mol) were added. The mixture was stirred at room temperature for 48 h to obtain the product, the reaction formula of which is as follows. The total yield was 80%, and the α / β ratio was less than 1:20.

[0093]

[0094] Its NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.82–7.74(m,2H),7.51(s,1H),7.39–7.30(m,2H),5.20(t,J=9.3Hz,1H),5.05(q,J=9 .8Hz,2H),4.88(d,J=10.0Hz,1H),4.20(d,J=3.5Hz,2H),3.73–3.65(m,1H),2.11(s,3H),2.09–1.92(m,9H). 13 C NMR (101MHz, CDCl3) δ170.61,170.16,169.39,169.34,144.07,139.81,133.89,124.95,124. 49,123.56,122.36,121.64,81.35,73.70,70.74,68.03,61.97,20.82,20.72,20.60,20.57.

[0095] Application Example 4. Preparation of p-Methoxyphenyl Tetraacetyl Glucose Selenoglucoside Product

[0096] 1-p-Toluenesulfonylselenotetraacetylglucose a5 (0.056 g, 0.0001 mol) obtained in Example 3 was dissolved in anhydrous tetrahydrofuran (2 ml), and p-methoxyphenylboronic acid (0.023 g, 0.00015 mol), cuprous oxide (I) (0.0028 g, 0.00002 mol), 2,2-bipyridine (0.0031 g, 0.00002 mol), and sodium acetate (0.00082 g, 0.0001 mol) were added. The mixture was stirred at room temperature for 12 h to obtain the product, which has the following reaction formula. The total yield is 93%, and the α / β ratio is less than 1:20.

[0097]

[0098] Its NMR data are as follows: 1 H NMR (400MHz, CDCl3) δ7.51(d,J=8.7Hz,2H),6.85–6.78(m,2H),5.15(t,J=9.3Hz,1H),4.94(dt,J=22.2,9.6Hz,2H),4.75(d,J =10.1Hz,1H),4.16(d,J=3.6Hz,2H),3.80(s,3H),3.64(dt,J=10.0,3.7Hz,1H),2.06(d,J=6.3Hz,6H),1.98(d,J=11.2Hz,6H). 13C NMR (101MHz, CDCl3) δ170.59,170.21,169.41,169.30,160.38,137.94,116.17, 114.59,80.45,73.89,70.68,68.11,62.04,55.26,20.83,20.74,20.60,20.57.

[0099] Compared with the currently reported selenoglycoside reagents, the phenylsulfone-substituted selenoglycoside presented in the present invention has significant activity, and the yield of the target product is as high as 91%.

[0100]

[0101] a Reaction conditions: Compound 1 (0.05 mmol), compound 2a (0.06 mmol), base (0.05 mmol), copper catalyst (0.01 mmol), ligand (0.01 mmol), solvent (1 ml) and stirring at room temperature for 12 hours.

[0102] b The yield was determined by nuclear magnetic resonance fluorine spectroscopy using trifluoromethoxybenzene as the internal standard.

[0103] The benzothienylselenoglycoside (Application Example 3) and p-methoxyphenylselenoglycoside (Application Example 4) obtained by the method of the present invention have good biological activity in the 7901 gastric cancer cell line, with IC50 of 10uM and 3.6uM, respectively.

[0104] The above description is only a preferred embodiment of the present invention. All equivalent changes and modifications made according to the scope of the patent application of the present invention should fall within the scope of the present invention.

Claims

1. A selenoglycosyl donor, characterized in that: The structure of the selenoglycosyl donor is as follows: 。 2. A method for preparing a selenoglycoside compound using the selenoglycosyl donor according to claim 1, characterized in that: The selenoglycoside compound comprises the following structure: 、 ； The method comprises: reacting a selenoglycoside donor with a glycoside acceptor to obtain a selenoglycoside compound; the structure of the glycoside acceptor is or .

3. The method according to claim 2, wherein: The molar ratio of the selenoglycosyl donor to the glycosyl acceptor is 5:1 to 1:

5.

4. The method according to claim 2, wherein: The reaction was carried out under nitrogen atmosphere.

5. The method according to claim 2, wherein: The reaction temperature is 0-100° C., and the reaction time is 12-48 hours.

6. The method according to claim 2, wherein: The reaction is carried out under the action of a copper catalyst, and the catalyst is selected from CuTc, CuCl, CuBr, CuOAc, Cu2S, CuBr2, and CuF2.

7. The method according to claim 2, wherein: The solvent for the reaction is selected from THF, DMF, DMSO, CH3OH, 1,2-DCE, and toluene.

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