Method for constructing 2-thio-2-deoxy glucosidic bond

Abstract

The invention relates to the technical field of medicines, and provides a method for constructing a 2-thio-2-deoxy glucosidic bond. According to the method, a glycosylation donor containing an o-alkynyl benzoate group at the 2-position and an alcohol or phenol receptor are subjected to a glycosylation reaction, and a glycosylation product is obtained. The glycosylation reaction conditions are mild, the 2-thio-2-deoxy glycosylation product can be obtained at a good yield, and the construction method of the 2-deoxy glycosidic bond is enriched.

Description

Technical Field

[0001] The invention belongs to the field of medical technology, and in particular relates to a method for preparing a compound containing a 2-thio-2-deoxyglycosidic bond. Background Art

[0002] Compared with mature and efficient nucleic acid and protein synthesis, efficient synthesis of carbohydrate compounds is still an important research topic in sugar chemistry today. Although a large number of glycosylation methods have been developed in recent years, many of them have been successfully applied to the synthesis of active sugar conjugates. However, these glycosylation methods not only have problems such as severe and harsh reaction conditions, but also often have limited substrate adaptability, which results in an embarrassing situation that the construction of a glycosidic bond usually requires careful screening of the offender to achieve the desired effect, which consumes a lot of time and experience. Especially the construction of some special glycosidic bonds, such as 2-deoxyglycosidic bonds (there are 6 2-deoxy sugars in the Cervimycin molecule). Therefore, the development of new glycosylation methods based on new activation principles to achieve the stereoselective and efficient construction of these special glycosidic bonds has become an urgent task in sugar chemistry research.

[0003] At present, the methods for constructing 2-deoxyglycosidic bonds can be mainly divided into the following five types: direct synthesis, indirect synthesis, addition to glycals, de novo synthesis, and anomeric alkylation-based approaches (refer to prior art document 1). Compared with other methods, direct synthesis is the most efficient, but due to the lack of 2-neighboring participating groups, the receptor can attack from the α or β direction at the same time, making the stereo configuration of the newly generated 2-deoxyglycosidic bond very difficult to control. The biggest advantage of indirect synthesis is the high stereoselectivity of the reaction, but its disadvantage is that it usually requires the introduction of thioether or halogen atoms such as I or Br at the 2-position before synthesis, which increases the steps and difficulty of the synthesis.

[0004] As a very important class of glycosyl donors, glucosinolate donors have many advantages such as easy synthesis, stable structure, convenient storage, and easy activation, and are widely used in oligosaccharide synthesis. However, glucosinolate donors often face a side reaction that cannot be underestimated during their application - glucosinolate migration (refer to prior art document 2). In 1986, KC Nicolaou first used DAST-induced 1,2-glucosinolate migration to achieve stereoselective construction of 2-deoxyglycosidic bonds (refer to prior art document 3), and applied it to the synthesis of apoptolide disaccharide building blocks (refer to prior art document 4).

[0005] On this basis, Boom et al. prepared 2-thio-2-deoxy sugar by introducing thiocarbonate as a leaving group at the 2-position and migrating the ethylthio group at the 1-position (refer to prior art documents 5 and 6). However, the reaction requires equivalent NIS activation, which also makes it incompatible with other non-terminal acceptors of sulfhydryl glycosides. Subsequently, the research group of Yu Biao, a researcher at the Shanghai Institute of Organic Chemistry, used rhamnose 2,3-position orthoester sulfhydryl glycoside to achieve the stereoselective construction of 2-thiodeoxyrhamnose (refer to prior art document 7), but unfortunately the scope of application of the donor is limited to rhamnose. Considering the instability of the orthoester, experiments on the migration of 1,2-sulfhydryl glycosides were also carried out by introducing 2,3-position cyclic thiocarbonyl esters (refer to prior art document 8), and it was applied to the synthesis of the sugar chain of Landomycin D (refer to prior art document 9).

[0006] In 2005, the research groups of Lipták (refer to prior art document 10) and Kanai (refer to prior art document 11) successively published their methods for synthesizing 2-deoxy-2-thioglucose azide by introducing a sulfonyl ester leaving group at the 2-position and using 1,2-thioglycoside migration. Subsequently, the research group of Lowary successfully achieved the construction of stereospecific 2-deoxyfuranosides by introducing epoxy at the 2,3 positions and then performing 1,2-thioglycoside migration (refer to prior art document 12). In addition to furanose, this method can also be used to construct glycosidic bonds of 2-deoxypyranose such as 2-deoxyrhamnose (refer to prior art document 13).

[0007] However, all of the above methods have disadvantages such as the need for equivalent catalysts, difficulty in preparing raw materials, poor stability, and a narrow range of substrate applications. Therefore, it is crucial to develop a method with donor stability, catalytic amount of the promoting system, mild reaction conditions, and wide substrate applicability.

[0008] Prior art document 1: Bennett, CS; Galan, MC, Methods for 2-Deoxyglycoside Synthesis. Chem. Rev. 2018, 118(17), 7931-7985.

[0009] Prior art document 2: Li, Z.; Gildersleeve, JC, Mechanistic studies and methods to prevent aglycon transfer of thioglycosides. J. Am. Chem. Soc. 2006, 128(35), 11612-9.

[0010] 3:Nicolaou,KC;Ladduwahetty,T.Randall,JL;Chucholowski,A.,Stereospecific 1,2-migrations of incarbohydrates.Stereocontrolled synthesis of alpha-and beta-2-deoxyglycosides.J.Am.Chem.Soc.1986,108(9),2466-7.

[0011] 4:Nicolaou,KC;Li,Y.;Phylactakidou,KC;Mitchell,HJ;Wei,H.-X.;Weyershausen,B.,Total Synthesis of Apoptolidin:Part1.Retrosynthetic Analysis and Construction of BuildingBlocks.Angw.Chem.Int.Ed.2001,40(20),3849-3854.

[0012] References 5:Zuurmond,HM;van der Klein,PAM:van der Marel,GA,van Boom,JH,Stereospecific 1,2-ethyl(phenyl)thio group migration in sugars:stereocontrolled synthesis of precursors toα-andβ-2-deoxyglycosides.Tetrahedron Lett.1992,33(15),2063-2066.

[0013] References 6:Zuurmond,HM;van der Klein,PAM:van der Marel,GA,van Boom,JH,A stereospecific approach towards the synthesis of 2-deoxyα-andβ-glycosides based on a 1,2-ethyl(phenyl)thio group migration.Tetrahedron1993,49(29),6501-6514.

[0014] Prior art document 7: Yu, B.; Yang, ZY, A novel and expeditious approach to thestereoselective synthesis of 2-S-ethyl(phenyl)-2-deoxy-beta-glycosides, readyprecursors to2-deoxy-beta-glycosides. Tetrahedron Lett. 2000, 41(16), 2961-2964.

[0015] Prior art document 8: Yu, B.; Yang, ZY, Stereoselective synthesis of2-S-phenyl-2-deoxy-beta-glycosides using phenyl 2,3-O-thionocarbonyl-1-thioglycosidedonors via1,2-migration and concurrent glycosidation.Org.Lett.2001,3(3),377-379.

[0016] Prior art document 9: Yang, XY; Yu, B., Synthesis of Landomycin D: Studies on the Saccharide Assembly. Synthesis-Stuttgart 2016, 48(11), 1693-1699.

[0017] Prior art document 10: Sajtos, F.; Lázár, L.; Borbás, A.; Bajza, I.; Lipták, A., Glycosyl azides of sugar 2-sulfonic acids. Tetrahedron Lett. 2005, 46(31), 5191-5194.

[0018] Prior art document 11: Maiereanu, C.; Kanai, A.; Weibel, JM; Pale, P., Synthesis of 2-deoxy-2-thiophenylglucosyl azides through 1,2thio migration of thiophenylmannosides. J Carbohyd Chem 2005, 24 (8-9), 831-842.

[0019] Prior art document 12: Hou, D.; Lowary, TL, Stereoselective synthesis of 2-deoxy-furanosides from 2,3-anhydro-furanosyl thioglycosides. Org. Lett. 2007, 9(22), 4487-4490.

[0020] Prior art document 13: Hou, D.; Lowary, TL, 2,3-Anhydrosugars in Glycoside Bond Synthesis. Application to 2,6-Dideoxypyranosides. J. Org. Chem. 2009, 74(6), 2278-2289. Summary of the invention

[0021] The object of the present invention is to provide a method for constructing a 2-thio-2-deoxyglycosidic bond, which has the advantages of simple operation, mild conditions, high stereoselectivity and regioselectivity, so as to prepare a compound containing a 2-thio-2-deoxyglycosidic bond.

[0022] Specifically, the method comprises the following steps:

[0023] In an inert gas environment, in an organic solvent, in the presence of a desiccant and a promoter, a glycosylation donor as shown in formula I and an acceptor as shown in formula S undergo a glycosylation reaction to obtain a glycosylation product as shown in formula P;

[0024]

[0025] in,

[0026] R 1 Selected from C 1 ~C 8 Alkyl, C 3 ~C 8 Cycloalkyl, aryl, ester group;

[0027] R2 Selected from acyl, C 1 ~C 8 Alkyl, aryl, silicon, hydrogen;

[0028] R 3 Selected from aryl, C 1 ~C 8 alkyl;

[0029] R 4 Selected from aryl, C 1 ~C 8 alkyl.

[0030] Due to the adoption of the above technical scheme, the embodiments of the present invention have the following beneficial effects: the glycosylation reaction conditions are mild, and 2-thio-2-deoxyglycosylated products can be obtained with good yields, wherein the reaction rate of the donor with p-methoxyphenylthioglycoside at the anomeric position is significantly faster than that of other types of glucosidase donors; this type of 2-thio-2-deoxyglycosylated product can be used for the rapid and stereospecific preparation of 2-deoxy-α-glycosidic bonds or 2-deoxy-β-glycosidic bonds after subsequent desulfurization. DETAILED DESCRIPTION

[0031] The prior art methods for constructing glycosidic bonds have problems such as the need for equivalent catalysts, difficulty in preparing raw materials, poor stability, and a narrow scope of substrate application. In order to solve at least one problem in the prior art, the present invention provides a glycosylation method for constructing 2-thio-2-deoxyglycosidic bonds based on Au(I)-catalyzed 2-o-alkynylbenzoate activation-induced 1-2-thioglycoside migration, the method comprising the following steps:

[0032] In an inert gas environment, in an organic solvent, in the presence of a desiccant and a promoter, a glycosylation donor as shown in formula I and an acceptor as shown in formula S undergo a glycosylation reaction to obtain a glycosylation product as shown in formula P;

[0033]

[0034] in,

[0035] R 1 Selected from C 1 ~C 8 Alkyl, C 3 ~C 8 Cycloalkyl, aryl, ester group;

[0036] R 2 Selected from acyl, C 1 ~C 8 Alkyl, aryl, silicon, hydrogen;

[0037] R 3 Selected from aryl, C 1 ~C8 alkyl;

[0038] R 4 OH is an alkyl or aryl alcohol or phenol, R 4 Selected from aryl, C 1 ~C 8 alkyl.

[0039] Furthermore, R 1 is selected from cyclopropyl, n-butyl; R 2 is selected from benzyl, benzoyl, silyl, benzylidene, and allyl; R 3 is selected from ethyl, phenyl, p-tolyl, p-methoxyphenyl, benzyl; R 4 Selected from ethyl, phenyl, p-tolyl, p-methoxyphenyl and benzyl.

[0040] Furthermore, the glycosylated donor as shown in formula I is selected from any one of the following compounds:

[0041]

[0042] Furthermore, the desiccant is a molecular sieve, preferably MS( Molecular Sieve).

[0043] Furthermore, the promoter is at least one of EDCI (N-(3-dimethylaminopropyl)-N"-ethylcarbodiimide hydrochloride) and DMAP (4-dimethylaminopyridine).

[0044] Furthermore, the glycosidation reaction is carried out under the catalytic action of a catalyst, wherein the catalyst is a compound or complex containing Au(I), preferably PPh 3 AHr 2 ([Bis(trifluoromethanesulfonimide)](triphenylphosphine)gold).

[0045] Furthermore, the temperature of the glycosidation reaction is -50 to 50°C; and the time of the glycosidation reaction is 2 to 72 hours.

[0046] Furthermore, the molar ratio of the glycosylated donor as shown in formula I to the acceptor as shown in formula S is 1:1 to 5:1, preferably 1.5:1; the molar ratio of the glycosylated donor as shown in formula I to the catalyst is 1:0.1 to 1:0.5, preferably 1:0.2; the molar volume ratio of the glycosylated donor as shown in formula I to the organic solvent is 0.001 to 0.1 mmol / mL, preferably 0.025 mmol / mL.

[0047] Furthermore, the organic solvent is dichloromethane (DCM).

[0048] Furthermore, the inert gas is selected from argon or nitrogen.

[0049] The glycosylation product shown in formula P obtained by the method may be one of the following compounds:

[0050]

[0051] In the present invention, the abbreviations of some groups represent the following meanings: ABz represents SMp represents p-methoxyphenylthio;

[0052] OMp represents p-methoxyphenoxy;

[0053] Bz represents benzoyl;

[0054] Bn represents benzyl;

[0055] TBS stands for tert-butyldimethylsilyl;

[0056] Allyl represents allyl.

[0057] Some typical embodiments are described below, and the present invention can be better understood according to the following embodiments. However, it is easy for those skilled in the art to understand that the contents described in the embodiments are only used to illustrate the present invention, and should not and will not limit the present invention described in detail in the claims.

[0058] Example 1: Preparation of Compound I1

[0059]

[0060] 2-OH-all-benzyl glucosinolate (165 mg, 0.30 mmol) was placed in a 10 mL round-bottom flask and heated under N 2 2 mL of dry DCM was added under protection to dissolve it, and EDCI (140 mg, 0.74 mmol, 2.5 eq), DMAP (18 mg, 0.15 mmol, 0.5 eq), and ABzOH (107 mg, 0.59 mmol, 2 eq) were added to the system in sequence, and reacted at room temperature for 4 h until TLC showed that the raw material was completely reacted. The mixture was then concentrated in vacuo and purified by silica gel (PE: EA = 6: 1) to obtain compound I1 (210 mg, 99%). The characterization data of compound I1 are as follows:

[0061] [α] D 25 = +10.5 (c 1.0, CHCl 3 );

[0062] 1 H NMR (400 MHz, CDCl 3)δ7.93(dd,J=1.6,8.0Hz,1H),7.53-7.49(m,3H),7.46(dt,J=1.6,7.6,9.2Hz,1H) ,7.39-7.28(m,9H),7.22-7.15(m,7H),6.77(dt,J=3.2,5.2,9.6Hz,2H),5.24(t,J= 9.2Hz,1H),4.82(d,J=10.8Hz,1H),4.72(s,2H),4.65-4.53(m,4H),3.85-3.74(m,6 H),3.71(t,J=9.6Hz,1H),3.59-3.55(m,1H),1.48-1.41(m,1H),0.89-0.83(m,4H);

[0063] 13 C NMR (100 MHz, CDCl 3 )δ164.9,160.1,138.4,138.1,137.9,136.4,134.4,131.8,131.6,130.7,128.6,128.5,128.4,128.3,128.2,128.0,127.8,127. 7(2C),127.1,125.0,122.0,114.6,114.4,99.4,86.2,84.5,79.6,77.8,75.5,75.2,74.9,73.6,72.6,69.1,55.4,9.0(2C),0.9;

[0064] HRMS(ESI)calcd for C 46 H 45 O 7 S[M+H] + 741.28860, found 741.28754.

[0065] By using a method substantially the same as Example 1 and changing the reactants, compounds of Formula I2 to Formula I12 can be obtained. Some examples are as follows.

[0066] Example 2: Preparation of Compound I4

[0067]

[0068] The yield of the compound represented by formula I4 is 82%, and its characterization data are as follows:

[0069] [α] D 25 = +44.2 (c 1.0, CHCl 3 );

[0070] 1 H NMR (400 MHz, CDCl 3 )δ8.01-7.98(m,2H),7.98(dd,J=1.2,8.0Hz,1H),7.88(dd,J=1.6,8.4Hz,2H),7.5 5-7.28(m,11H),6.91(dt,J=3.2,5.2,10.0Hz,2H),5.95(dd,J=1.6,3.6Hz,1H),5. 85(dd,J=3.6,10.0Hz,1H),5.72(t,J=9.6Hz,1H),5.54(d,J=1.6Hz,1H),4.73-4.6 6(m,1H),3.81(s,3H),1.43-1.35(m,1H),1.38(d,J=6.0Hz,3H),0.81-0.68(m,4H);

[0071] 13 C NMR (100 MHz, CDCl 3 )δ165.9,165.6,164.9,160.2,135.3,134.4,133.5,133.3,132.1,130.9,130.5,129.9,129.4,129.3,128. 6,128.5,127.3,125.3,123.6,115.0,100.1,86.9,77.4,74.3,72.2,70.4,68.1,55.5,17.7,9.0(2C),0.7;

[0072] HRMS(ESI)calcd for C 39 H 34 O 8 S[M+H] + 663.20527, found 663.20548.

[0073] Example 3: Preparation of Compound I5

[0074]

[0075] The yield of the compound represented by formula I5 is 92%, and its characterization data are as follows:

[0076] [α] D 25 = -2.2 (c 1.0, CHCl 3 );

[0077] 1 H NMR (400 MHz, CDCl 3)δ7.96(dd,J=1.6,8.0Hz,1H),7.53-7.43(m,6H),7.40-7.32(m,4H),6.86(dt,J=3.2,5.2,9.6H z,2H),5.82-5.72(m,1H),5.56(s,1H),5.20-5.15(m,2H),5.05(dq,J=1.2,2.8,4.4,10.4Hz,1H) ,4.74(d,J=10.0Hz,1H),4.43(dd,J=5.2,10.8Hz,1H),4.34-4.29(m,1H),4.15-4.09(m,1H),3. 84-3.78(m,5H),3.69(t,J=9.2Hz,1H),3.55-3.49(m,1H),1.50-1.43(m,1H),0.91-0.83(m,4H);

[0078] 13 C NMR (100 MHz, CDCl 3 )δ164.8,160.4,137.3,136.8,134.7,134.4,131.8,131.8,130.5,129.1,128.4,127.2,126.1,124. 8,121.4,117.2,114.5,101.3,99.3,86.9,81.1,80.3,74.7,73.7,72.2,70.8,68.7,55.4,9.0,0.8;

[0079] HRMS(ESI)calcd for C 35 H 34 O 7 SNa[M+Na] + 621.19230, found 621.19261.

[0080] Example 4: Preparation of Compound I6

[0081]

[0082] The yield of the compound represented by formula I6 is 76%, and its characterization data are as follows:

[0083] [α] D 25 = +155.4 (c 1.0, CHCl 3 );

[0084] 1 H NMR (400 MHz, CDCl 3)δ8.05-7.88(m,8H),7.59-7.22(m,13H),6.75(dt,J=3.2,5.2,10.0Hz,2H), 6.08(t,J=6.0Hz,1H),6.00(dd,J=1.6,3.2Hz,1H),5.91(dd,J=3.2,6.0Hz,1H ),5.64(d,J=1.6Hz,1H),5.06-5.02(m,1H),4.65(dd,J=2.4,12.0Hz,1H),4.5 9(dd,J=5.6,12.0Hz,1H),3.74(s,3H),1.39-1.33(m,1H),0.78-0.64(m,4H);

[0085] 13 C NMR (100 MHz, CDCl 3 )δ166.3,165.6,165.6,164.8,160.2,135.2,134.5,133.6,133.4,133.2,132.2,130.7,130.5,130.0(2C),129.9(2C),129.1,12 9.0,128.6,128.5,128.5,127.3,125.4,122.9,114.9,100.2,86.9,77.4,74.3,71.8,70.4,69.8,67.6,63.4,55.4,9.0,8.9,0.7;

[0086] HRMS(ESI)calcd for C 46 H 38 O 10 S[M+Na] + 805.2088, found 805.20834.

[0087] Example 5: Preparation of Compound I7

[0088]

[0089] The yield of the compound represented by formula I7 is 92%, and its characterization data are as follows:

[0090] 1 H NMR (400 MHz, CDCl 3)δ7.89(dd,J=1.2,8.0Hz,1H),7.50(dd,J=1.2,7.6Hz,1H),7.43-7.28(m, 10H),7.22-7.16(m,6H),5.36(t,J=9.2Hz,1H),4.85(d,J=10.8Hz,1H),4. 74(s,2H),4.65-4.53(m,4H),3.87-3.71(m,4H),3.59-3.55(m,1H),2.84- 2.68(m,1H),1.52-1.43(m,1H),1.28(t,J=7.6Hz,4H),0.92-0.84(m,4H);

[0091] 13 C NMR (100 MHz, CDCl 3 )δ165.0,138.4,138.2,138.1,134.4,131.8,131.6,130.7,128.6,128.5,128.4,128.2(2C),128.0(2C),127. 8,127.7,127.1,125.0,99.4,84.6,83.5,79.8,78.0,75.4,75.3,74.8,73.6,72.6,69.1,23.7,15.1,9.0(2C).

[0092] Example 6: Preparation of Compound I8

[0093]

[0094] The yield of the compound represented by formula I8 is 85%, and its characterization data are as follows:

[0095] [α] D 25 = +4.8 (c 1.0, CHCl 3 );

[0096] 1 H NMR (400 MHz, CDCl 3)δ7.89(dd,J=1.2,7.6Hz,1H),7.49-7.25(m,15H),6.86(dt,J=3.2,5.2,10.0Hz,2H),5.87(dd ,J=2.0,3.6Hz,1H),5.40(d,J=1.6Hz,1H),4.94(d,J=10.8Hz,1H),4.83(d,J=11.2Hz,1H),4.65 (d,J=9.8Hz,1H),4.60(d,J=11.2Hz,1H),4.34-4.27(m,1H),4.03(dd,J=3.2,9.2Hz,1H),3.78 (s,3H),3.62(t,J=9.6Hz,1H),1.52-1.45(m,1H),1.37(d,J=6.0Hz,3H),0.85(d,J=6.4Hz,4H);

[0097] 13 C NMR (100 MHz, CDCl 3 )δ165.2,160.0,138.5,137.9,135.0,134.3,131.8,131.6,130.5,128.5(2C),128.4,128.2,127.9,127.8,127.1,125.1,12 4.2,114.8,99.8,87.2(d,J=4Hz,1C),80.4,78.5,75.5,74.5,71.8,71.0,69.0,55.5(d,J=4.5Hz,1C),18.07,9.1,9.0,0.84;

[0098] HRMS(ESI)calcd for C 39 H 38 O 6 S[M+K] + 673.202621, found 673.202881.

[0099] Example 7: Preparation of Compound P1

[0100]

[0101] The donor compound I1 (104 mg, 0.15 mmol) and the acceptor 6-OH-2,3,4-tribenzyl glucose methyl glycoside (47 mg, 0.1 mmol) were placed in a 25 mL eggplant-shaped bottle and an appropriate amount of activating MS and 4 mL of dry DCM were stirred at room temperature for 30 min and PPh 3 AHr 2(22 mg), react at 30°C until TLC tracking shows that the receptor is completely consumed. 0.1 mL Et3N was added to the above reaction system to quench the reaction, the molecular sieves in the system were removed by suction and concentrated under reduced pressure, and column chromatography was used to separate to obtain compound P1 (90 mg, 88%). The characterization data of compound P1 are as follows:

[0102] 1 H NMR (400 MHz, CDCl 3 )δ7.38(dd,J=2.4,6.8Hz,2H),7.29-7.11(m,28H),7.07-7.05(m,2H),6.71(dd,J=2.4,6.8Hz,2H),4.9 6(d,J=1.6Hz,1H),4.90(d,J=10.8Hz,1H),4.84(d,J=10.4Hz,1H),4.79(d,J=10.8Hz,1H),4.71-4.66(m ,2H),4.60-4.55(m,3H),4.47-4.35(m,5H),4.11(dd,J=4.8,9.2Hz,1H),3.89(t,J=9.2Hz,1H),3.82(t, J=9.6Hz,1H),3.73-3.68(m,5H),3.60-3.55(m,2H),3.50-3.47(m,3H),3.35-3.28(m,2H),3.19(s,3H);

[0103] 13 C NMR (100 MHz, CDCl 3 )δ138.7,138.6,138.5,138.3,138.2,138.1,136.0,128.6,128.5,128.4(2C),128.3,128.1(2C),128.0,127.8(2C),127.7,127.6,127. 5,125.6,114.6,100.3,97.8,82.2,80.1,78.3,77.6,75.9,75.1,75.0,74.9,73.4,73.3,71.9,71.3,69.8,69.1,65.8,55.4,55.2,54.1.

[0104] By using a method substantially the same as Example 7 and changing the reactants, compounds of Formula P2-P31 can be obtained. Some examples are as follows.

[0105] Example 8: Preparation of Compound P3

[0106]

[0107] The yield of compound P3 is 88%, and its characterization data are as follows:

[0108] 1 H NMR (400 MHz, CDCl 3 )δ7.46(dt,J=2.4,4.4,8.0Hz,2H),7.38-7.25(m,18H),7.18-7.17(m,2H),6.81( dt,J=2.8,4.4,8.0Hz,2H),5.30(t,J=3.2Hz,1H),5.15(d,J=1.6Hz,1H),5.11(d, J=10.0Hz,1H),5.06(d,J=10.0Hz,1H),4.89(d,J=8.8Hz,1H),4.71(d,J=9.6Hz,1 H),4.64(d,J=9.2Hz,1H),4.59(d,J=9.2Hz,1H),4.54-4.48(m,2H),4.21(dd,J=3 .2Hz,1H),3.96-3.87(m,2H),3.81-3.75(m,4H),3.70(dd,J=1.6,8.8Hz,1H),3.4 8(dd,J=1.6,3.6Hz,1H),3.21(dd,J=3.2,9.2Hz,1H),2.93(dd,J=3.6,11.2Hz,1H ),2.02(dt,J=3.6,11.2,14.4Hz,1H),1.84-1.82(m,2H),1.76-1.47(m,10H),1.4 0-1.12(m,12H),1.06-1.01(m,1H),0.94-0.77(m,14H),0.71(s,3H),0.60(s,3H);

[0109] 13 C NMR (100 MHz, CDCl 3)δ177.5,159.4,143.8,138.6,138.5,138.2,136.5,135.2,128.5,128.4(3C),128.3,128.2(2C), 128.1,128.0,127.7,127.7(2C),127.5,126.1,122.5,114.6,96.6,82.8,78.9,77.4,75.2,75.0, 73.3,72.3,71.6,69.3,66.0,55.5,55.4,55.0,47.6,46.8,45.9,41.7,41.4,39.4,38.4,38.0,36.9,33.9,33.2,32.8,32.4,30.8,28.8,27.7,26.0,23.7,23.5,23.1,21.9,18.3,17.0,16.6,15.4;

[0110] Example 9: Preparation of Compound P6

[0111]

[0112] The yield of compound P6 is 99%, and its characterization data are as follows:

[0113] [α] D 25 = -28.3 (c 1.0, CHCl 3 );

[0114] 1 H NMR (400 MHz, CDCl 3 )δ7.38-7.20(m,29H),7.17-7.15(m,3H),6.74(dd,J=2.0,6.4Hz,2H),4.98(d,J=10.4Hz,1H),4 .94(d,J=11.2Hz,1H),4.83-4.74(m,3H),4.70-4.66(m,2H),4.60-4.56(m,3H),4.52-4.45(m,2H ),4.42-4.38(m,2H),4.23(dd,J=3.2,10.8Hz,1H),4.07(t,J=9.2Hz,1H),3.77-3.68(m,6H),3.6 4-3.55(m,2H),3.52-3.45(m,2H),3.35(s,3H),3.31-3.22(m,2H),2.99(dd,J=8.8,10.8Hz,1H);

[0115] 13 C NMR (100 MHz, CDCl 3)δ159.1,139.6,138.7,138.5,138.4,138.3,138.0,133.7,128.7,128.5 (2C),128.4,128.2,128.1(2C),128.0,127.9,127.8(2C),127.6,127.4,1 27.2,126.8,114.4,102.1,98.4,83.1,80.6,79.5,79.1,77.4,76.2,75. 4,75.3,75.1,74.8,73.7,73.6,73.5,69.8,68.9,68.6,58.6,55.4,55.3;

[0116] HRMS(ESI)calcd for C 62 H 66 O 11 SK[M+K] + 1057.3963, found 1057.3958

[0117] Example 10: Preparation of Compound P7

[0118]

[0119] The yield of compound P7 is 87%, and its characterization data are as follows:

[0120] [α] D 25 = -21.2 (c 1.0, CHCl 3 );

[0121] 1 H NMR (400 MHz, CDCl 3 )δ7.44(s,1H),7.39-7.22(m,17H),6.70(dt,J=3.2,5.2,10.0Hz,2H),6.50(s,1H),6.37(s,2H) ,5.98(dd,J=1.6,3.2Hz,1H),5.09(d,J=10.4Hz,1H),4.95-4.85(m,4H),4.64-4.56(m,4H),4.4 7(d,J=8.8Hz,1H),4.16(dd,J=8.8,10.4Hz,1H),3.82(s,3H),3.77(s,3H),3.76-3.64(m,9H),3 .57-3.58(m,2H),3.10(dd,J=9.2,11.2Hz,1H),3.03-2.94(m,1H),2.84(dd,J=4.4,14.4Hz,1H);

[0122] 13 C NMR (100 MHz, CDCl 3 )δ174.3,159.4,152.7,147.8,147.5,138.3,138.2,138.0,137.1,135.5,13 4.1,131.7,130.8,128.6,128.5,128.5,128.2,128.1,128.0,127.9,127.7, 127.7,126.0,114.5,109.3,109.0,108.1,103.0,101.4,83.6,79.8,79.2,76.4,75.1,75.1,73.7,71.8,69.1,60.8,58.8,56.2,55.4,45.7,44.0,39.2;

[0123] HRMS(ESI)calcd for C 56 H 56 O 13 S[M+H] + 969.35199, found 969.35193.

[0124] Example 11: Preparation of Compound P9

[0125]

[0126] The yield of compound P9 is 98%, and its characterization data are as follows:

[0127] [α] D 25 = +36.1 (c 1.0, CHCl 3 );

[0128] 1 H NMR (400 MHz, CDCl 3)δ7.51(d,J=8.4Hz,2H),7.42-7.22(m,25H),6.69(d,J=8.4Hz,2H),5.08(d,J=10.4Hz,1H),4.99(d,J=10.8 Hz,1H),4.88-4.79(m,4H),4.72-4.61(m,4H),4.56(d,J=11.2Hz,1H),4.41(d,J=8.8Hz,1H),4.11(dd,J=4.0 ,11.6Hz,1H),4.00(t,J=9.2Hz,1H),3.75(d,J=10.4Hz,2H),3.66(s,3H),3.64-3.55(m,2H),3.48(dd,J=8.8 ,11.6Hz,1H),3.40-3.32(m,4H),3.23(t,J=8.8Hz,1H),3.01(dd,J=9.2,11.2Hz,1H),1.27(d,J=6.0Hz,3H);

[0129] 13 C NMR (100 MHz, CDCl 3 )δ159.3,139.1,138.6,138.5,138.3,138.1,135.0,128.6,128.5,128.4(2C),128.2,128.1(2C),,128.0,127.9,127.8,127.7,1 27.6,125.6,114.3,103.0,98.1,85.0,82.8,82.0,80.1,77.6,76.1,75.7,75.3,75.0,73.5,70.9,70.4,67.4,57.7,55.3,17.9;

[0130] HRMS(ESI)calcd for C 55 H 60 O 10 SNa[M+Na] + 935.3805, found 935.3784.

[0131] Example 12: Preparation of Compound P10

[0132]

[0133] The yield of compound P10 is 99%, and its characterization data are as follows:

[0134] [α] D 25 = +58.1 (c 1.0, CHCl 3 );

[0135] 1 H NMR (400 MHz, CDCl 3 )δ7.49(dd,J=2.0,6.4Hz,2H),7.45-7.25(m,23H),6.76(dd,J=2.0,6.4Hz,2H),5.26(d,J=10.4Hz,1H),5.06(dd,J=2.8 ,10.4Hz,2H),4.92(d,J=9.2Hz,1H),4.86(dd,J=4.0,10.4Hz,2H),4.79(d,J=12.0Hz,1H),4.66-4.55(m,4H),4.46(d,J= 12.0Hz,1H),4.07(t,J=9.2Hz,1H),3.84(t,J=9.6Hz,1H),3.77-3.74(m,4H),3.60-3.53(m,2H),3.48(dd,J=5.6,10.8H z,1H),3.40-3.33(m,4H),3.27-3.20(m,1H),3.14(t,J=8.8Hz,1H),2.87(dd,J=9.2,11.2Hz,1H),1.17(d,J=6.0Hz,3H);

[0136] 13 C NMR (100 MHz, CDCl 3 )δ159.1,139.1,138.7,138.5,138.1(2C),134.5,128.6,128.5,128.4,128.3(2C),128.2(2C),128.1(3C),128.0,127.8,127.7,127 .6,127.5,127.3,114.4,102.5,97.8,85.2,83.4,81.7,80.6,76.3,75.4,75.2,73.4(2C),70.8,69.8,69.5,59.2,55.4,55.3,17.9;

[0137] HRMS(ESI)calcd for C 55 H 60 O 10 SNa[M+Na] + 935.3805, found 935.3802

[0138] Example 13: Preparation of Compound P11

[0139]

[0140] The yield of compound P11 was 87%, and its characterization data were as follows:

[0141] [α] D 25 = +27.1 (c 1.0, CHCl 3 );

[0142] 1 H NMR (400 MHz, CDCl 3 )δ7.52(dt,J=3.2,5.2,10.0Hz,2H),7.37-7.20(m,15H),6.78(dt,J=3.2,5.6,10.0Hz,2H), 5.06(d,J=10.4Hz,1H),4.86(dd,J=10.4,12.8Hz,2H),4.69(d,J=8.8Hz,1H),4.60-4.52(m, 3H),3.76(s,3H),3.74(dd,J=2.0,10.8Hz,1H),3.63(dd,J=5.6,10.4Hz,1H),3.56-3.43(m, 3H),3.09(dd,J=9.2,10.8Hz,1H),2.15-2.12(m,3H),1.90-1.81(m,6H),1.65-1.58(m,6H);

[0143] 13 C NMR (100 MHz, CDCl 3 )δ158.9,138.6,138.5,138.2,133.7,128.5,128.4,128.4,128.2,128.0,127.9,127.7(2C),127.6 ,127.5,114.3,96.9,83.9,79.6,76.1,75.5,75.0,74.5,73.5,69.6,58.8,55.5,42.7,36.4,30.8;

[0144] HRMS(ESI)calcd for C 44 H 50 O 6 S[M+K] + 745.29652,found745.29629

[0145] Example 14: Preparation of Compound P12

[0146]

[0147] The yield of compound P12 was 80%, and its characterization data were as follows:

[0148] [α] D 25 =+9.6(c 1.0,CHCl 3 );

[0149] 1 H NMR(400MHz,CDCl 3 )δ7.50(dt,J=3.2,5.2,10.0Hz,2H),7.42-7.39(m,2H),7.35-7.27(m,11H),7.21-7.18(m,2H),6.80(dt,J=3.2,5.2,10.0Hz,2H),5.70(s,1H),5.07(d,J=10.4Hz,1H),4.88(d,J=10.4Hz,1H),4.82(d,J=10.8Hz,1H),4.74-4.71(m,2H),4.63-4.53(m,3H),4.35(d,J=8.8Hz,1H),4.24(d,J=11.2Hz,1H),3.97(d,J=11.6Hz,1H),3.78(s,3H),3.77-3.60(m,3H),3.54(dd,J=8.8,10.8Hz,1H),3.43-3.39(m,1H),3.07(dd,J=8.8,10.8Hz,1H),2.18-2.12(m,4H),1.86-1.79(m,1H),1.75(s,3H),0.91-0.81(m,2H);

[0150] 13 C NMR(100MHz,CDCl 3 )δ159.4,150.1,138.5,138.4,138.2,135.2,134.0,128.6,128.5,128.1,128.0,127.9,127.8,127.7,125.5,125.0,114.4,108.7,102.2,83.1,79.5,76.0,75.0,74.9,73.7,73.6,69.1,57.2,55.5,41.2,30.7,27.6,26.7,20.9;

[0151] HRMS(ESI)calcd for C 44 H 56 O 6 S[M+NH 4 ] + 724.36719,found 724.36673.

[0152] Example 15: Preparation of Compound P13

[0153]

[0154] The yield of compound P13 is 99%, and its characterization data are as follows:

[0155] [α] D 25 =-2.5(c 1.0,CHCl 3 );

[0156] 1 H NMR (400 MHz, CDCl 3 )δ7.46-7.43(m,4H),7.37-7.27(m,18H),6.74(dd,J=2.4,6.8Hz,2H),6.03-5.93(m,1H),5.52(s,1H),5.33(dq,J=1.6,3.6,5.2,17.2 Hz,1H),5.18-5.14(m,1H),4.99(d,J=10.8Hz,1H),4.94(d,J=11.2Hz,1H),4.85-4.78(m,3H),4.65(d,J=12.0Hz,1H),4.59(d,J=3.6H z,1H),4.46-4.41(m,2H),4.29(dd,J=5.2,10.4Hz,1H),4.20-4.15(m,1H),4.10(dd,J=2.4,11.2Hz,1H),4.01(t,J=10.0Hz,1H),3.81 -3.65(m,7H),3.62(t,J=9.2Hz,1H),3.47(dd,J=3.6,9.6Hz,1H),3.41-3.35(m,4H),3.30-3.24(m,1H),3.04(dd,J=8.8,10.4Hz,1H);

[0157] 13 C NMR (100 MHz, CDCl 3 )δ159.4,139.0,138.8,138.3,137.4,135.2,135.1,129.0,128.6,128.5,128.4,128.3,128.2,128.0(2C),127.7(2C),127.6,126.0,1 24.5,116.9,114.5,103.6,101.2,98.3,82.8,82.2,79.9,78.5,77.4,75.7,74.9,74.2,73.6,69.7,68.7,68.5,65.8,55.9,55.4,55.3.

[0158] Example 16: Preparation of Compound P19

[0159]

[0160] The yield of compound P19 was 97%, and its characterization data were as follows:

[0161] 1 H NMR (400 MHz, CDCl 3 )δ7.53-7.47(m,4H),7.39-7.29(m,8H),6.87(dq,J=3.2,5.2,9.6Hz,2H),5.96(m,1H),5.63(s,1H),5.31-5.26(m,2H),5.19(dq,J=1 .2,2.8,4.4,10.4Hz,1H),5.12-5.02(m,3H),4.24-4.14(m,4H),4.07(t,J=9.2Hz,1H),4.00(ddd,J=4.4,9.6,14.0Hz,1H),3.86-3.81 (m,4H),3.52(dd,J=1.2,4.8Hz,1H),3.16(d,J=4.4,11.6Hz,1H),2.92(d,J=4.4,14.0Hz,1H),2.01-1.94(m,1H),1.84-1.81(m,2H),1 .74(dd,J=4.4,13.6Hz,1H),1.64-1.21(m,15H),1.11(s,3H),1.05-0.99(m,4H),0.91-0.82(m,10H),0.75-0.68(m,4H),0.59(s,3H);

[0162] 13 C NMR (100 MHz, CDCl 3)δ177.4,159.5,143.7,137.5,136.4,135.1,134.6,128.8,128.4,128.1,127.9(2C),12 6.0,125.9,122.3,117.1,114.6,101.4,97.7,83.6,79.7,77.2,74.3,71.2,68.8,65.9, 64.8,56.5,55.4(2C),47.5,46.7,45.8,41.6,41.3,39.3,38.3,38.0,36.8,33.8,33.1, 32.7,32.3,30.7,28.6,27.6,26.9,25.8,23.6,23.4,23.0,22.0,18.2,16.9,16.5,15.3.

[0163] Example 17: Preparation of Compound P26

[0164]

[0165] The yield of compound P26 is 37%, and its characterization data are as follows:

[0166] [α] D 25 =29.9(c 1.0,CHCl 3 );

[0167] 1 H NMR (400 MHz, CDCl 3 )δ7.39-7.27(m,25H),7.25-7.16(m,5H),5.37(d,J=2.4Hz,1H),5.11(d,J=11.6Hz,1H) ,4.85(d,J=11.2Hz,1H),4.71-4.65(m,2H),4.61-4.53(m,6H),4.48-4.40(m,3H),4.13 -4.10(m,1H),3.86-3.81(m,3H),3.75-3.71(m,4H),3.65-3.61(m,1H),3.56-3.52(m,2 H),3.39(s,3H),3.17(dd,J=2.0,4.0Hz,1H),3.40-2.20(m,2H),1.03(t,J=7.2Hz,1H);

[0168] 13 C NMR (100 MHz, CDCl 3)δ138.9,138.5(2C),138.4,138.0,128.6,128.5,128.4,128.4,128.3,128.1,128.0,127.9,127.8,127.7,127.6,127.5(2C),126.9, 103.5,97.8,81.4,80.2,79.1,78.1,77.4,75.4,75.1,74.9,73.5,73.4,73.3,73.0,71.9,70.0,69.4(2C),55.4,50.224,27.4,14.7;

[0169] HRMS(ESI)calcd for C 57 H 64 O 10 S[M+Na] + 963.41179, found 963.41111

[0170] The above are only specific implementations of the present application, but the protection scope of the present application is not limited thereto. Any technician familiar with the technical field can easily think of changes or substitutions within the technical scope disclosed in the present application, which should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A method for preparing a glycosylated product as shown in formula P, comprising the following steps: In an inert gas environment, in an organic solvent, in the presence of a desiccant and a promoter, a glycosylation donor as shown in formula I and an acceptor as shown in formula S undergo a glycosylation reaction to obtain a glycosylation product as shown in formula P; in, R1 is selected from C1-C8 alkyl, C3-C8 cycloalkyl, aryl, ester group; R2 is selected from acyl, C1-C8 alkyl, aryl, silicon, hydrogen; R3 is selected from aryl, C1-C8 alkyl; R4 is selected from aryl, C1-C8 alkyl.

2. The method according to claim 1, characterized in that: The R1 is selected from cyclopropyl and n-butyl; the R2 is selected from benzyl, benzoyl, silicon, benzylidene and allyl; the R3 is selected from ethyl, phenyl, p-tolyl, p-methoxyphenyl and benzyl; the R4 is selected from ethyl, phenyl, p-tolyl, p-methoxyphenyl and benzyl.

3. The method according to claim 1, characterized in that: The glycosylated donor as shown in formula I is selected from any of the following compounds:

4. The method according to claim 1, characterized in that: The desiccant is a molecular sieve.

5. The method according to claim 1, characterized in that: The promoter is at least one of EDCI and DMAP.

6. The method according to claim 1, characterized in that: The glycosidation reaction is carried out under the catalytic action of a catalyst, and the catalyst is a compound or complex containing Au(I).

7. The method according to claim 1, characterized in that: The temperature of the glycosylation reaction is -50 to 50°C; the time of the glycosylation reaction is 2 to 72 hours.

8. The method according to claim 1, characterized in that: The molar ratio of the glycosylated donor as shown in formula I to the acceptor as shown in formula S is 1:1 to 5:1; the molar ratio of the glycosylated donor as shown in formula I to the catalyst is 1:0.1 to 1:0.5; the molar volume ratio of the glycosylated donor as shown in formula I to the organic solvent is 0.001 to 0.1 mmol / mL.

9. The method according to claim 1, characterized in that: The organic solvent is dichloromethane.

10. The method according to claim 1, characterized in that: The inert gas is selected from argon or nitrogen.

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