A highly stereoselective method for the construction of alpha-xylopyranosidic linkages

Abstract

The application discloses a kind of high stereoselectivity of alpha-xylopyranoside bond construction method, belongs to the technical field of sugar chemistry.The application uses full benzyl protected xylose trichloroacetimidate as glycosyl donor, by screening catalytic system, donor / acceptor ratio, additive type and molecular sieve type, optimize with trimethyl iodine silane as activating agent, triphenylphosphine oxide as additive high alpha-stereoselectivity glycosylation method.The method is mild in reaction condition, easy to operate, realizes the high stereoselectivity construction of 1,2-cis xylopyranoside bond without the action of participating group.Moreover, the method can be suitable for a variety of xylose donors with different protecting groups and a variety of glycosyl acceptors, to provide an effective means for efficient construction of a variety of alpha-xyloside and arabinoxylan modified by arabian mycin.

Description

Technical Field

[0001] This invention belongs to the field of glycochemistry technology, specifically relating to a method for constructing α-xylose-pyranoside bonds with high stereoselectivity. Background Technology

[0002] The information disclosed in this background section is intended only to enhance understanding of the overall background of the invention and is not necessarily to be construed as an admission or in any way implying that such information constitutes prior art known to those skilled in the art.

[0003] Carbohydrates are a class of compounds widely found in plants, animals, and microorganisms, playing an irreplaceable and vital role in life activities. Given their significant value in biological activity research and pharmaceutical applications, the preparation of carbohydrates with uniform and controllable structures is of paramount importance.

[0004] Glycosylation is the most critical reaction in the synthesis of carbohydrate compounds. Regioselectivity and stereoselectivity are issues that arise during glycosylation. Regioselectivity can theoretically be differentiated by different protecting groups, but the construction of glycosidic bonds with specific stereoconfigurations has progressed slowly. Currently, the construction of common 1,2-trans glycosidic bonds can be relatively well solved using the neighboring group participation strategy, but the construction of 1,2-cis glycosidic bonds, especially α-xyloside bonds where the anodic effect is unfavorable, remains a significant challenge.

[0005] Most current methods for constructing α-xyloside bonds suffer from poor stereoselectivity and limited substrate applicability, making them difficult to apply in practical synthesis. The most widely used glycosyl donor for constructing α-xylopyranosides is the 2,3,4-O-tribenzyl (Bn)-protected xylopyranosyl donor. However, this substrate does not exhibit good stereoselectivity and is generally limited to specific glycosyl acceptors; furthermore, the β-configuration byproducts generated during the reaction pose significant challenges to purification. Another frequently used strategy for α-xylosylation is the use of 3-O-acetyl-2,4-O-dibenzylxyloside, where the acetyl group at the 3-position can promote the formation of the α-configuration product through remote interaction; however, this method only exhibits good stereoselectivity under limited circumstances. Furthermore, in 2020, Junichi Tamura's group in Japan proposed a method for constructing α-xyloside bonds using an intramolecular aglycone transfer strategy (IAD) mediated by 4-methoxybenzyl ether. This method can yield a single α-configuration xyloside product, but the yield is low, and the preparation of the glycosyl donor involves numerous steps, resulting in low overall synthetic efficiency. In addition, in 2021, Ding Kan's group proposed a method for selectively synthesizing α-configuration xylosylylation using a conformational control strategy and a hydrogen bond-mediated aglycone transfer method (HAD). However, this method requires cumbersome protecting group operations to introduce pico protecting groups to achieve intermolecular hydrogen bonding, and the concentration requirements are relatively strict. The introduction and removal of specific protecting groups require additional steps, leading to a lengthy synthetic process. Therefore, it can be concluded that there are various limitations in the synthesis of α-xyloside bonds, and there is an urgent need to develop a novel, efficient, and universal method for constructing α-xylopyranoside bonds. Summary of the Invention

[0006] To address the shortcomings of existing technologies and achieve efficient and highly stereoselective construction of α-xylose-pyranoside bonds, this invention provides a highly stereoselective method for α-xylose-pyranoside bond construction. Using fully benzyl-protected xylose trichloroacetylimine ester as the glycosyl donor, and through screening the catalytic system, donor / acceptor ratio, additive type, and molecular sieve type, a highly stereoselective glycosylation method was optimized, employing trimethyliodosilane (TMSI) as the activator and triphenylphosphine oxide (Ph3PO) as the additive. This method features mild reaction conditions, ease of operation, and achieves highly stereoselective construction of 1,2-cis xylose-pyranoside bonds without the influence of participating groups.

[0007] To achieve the above objectives, the technical solution of the present invention is as follows:

[0008] A first aspect of the present invention provides a method for constructing α-xylopyranoside bonds with high stereoselectivity, comprising the following steps:

[0009] Using trimethyliodosilane as an activator and triphenylphosphine, diphenylmethylphosphine, or tri(N,N-tetramethylene)phosphonamide as additives, a glycosylation reaction is carried out between a glycosyl donor and a glycosyl acceptor to obtain a glycosylated product.

[0010] The glycosyl donor is an O-glycosyl trichloroacetylimine ester donor with different protecting groups; the protecting group of the glycosyl donor is a protecting group that does not participate in the interaction of the adjacent group.

[0011] A second aspect of the present invention provides the application of the above-described method for constructing highly stereoselective α-xylopyranoside bonds in glycosylation reactions, wherein the application is for the highly stereoselective construction of 1,2-cis-xylopyranoside bonds.

[0012] The beneficial effects of this invention are as follows:

[0013] This invention utilizes xylose trichloroacetylimine ester protected by a protecting group as a glycosyl donor. By screening the catalytic system, donor / acceptor ratio, additive type, and molecular sieve type, a highly α-stereoselective glycosylation method was optimized, using trimethyliodosilane (TMSI) as the activator and triphenoxyphosphine (Ph3PO) as the additive. This method features mild reaction conditions and is easy to operate. It achieves highly stereoselective construction of 1,2-cis xylose-pyranoside bonds without the influence of participating groups, yielding high-yield glycosylated products.

[0014] Because the target product is a disaccharide containing an α-glycosidic bond, a protecting group involving neighboring groups cannot be selected. Therefore, this invention chose benzyl as the protecting group. The advantages of all-benzyl protection are as follows: firstly, all-benzyl protection of xylose donors has higher activity; secondly, all-benzyl protection of xylose is convenient and simple to prepare. This invention also selected trichloroacetilimate as the leaving group because the trichloroacetilimate glycosyl donor is simple to prepare and has good glycosylation reaction effect.

[0015] The method of this invention is applicable to various xylose donors with different protecting groups and various glycosyl acceptors, and exhibits good yield and stereoselectivity. When using fully benzyl-protected xylose as the glycosyl donor and reacting with different acceptors, the reactivity is good. Replacing the protecting group of the xylose donor with other protecting groups, such as benzoyl, acetyl, 2-naphthylmethyl, acetylpropionyl, etc., and reacting with the corresponding acceptor, also yields high stereoselectivity and yield. Attached Figure Description

[0016] The accompanying drawings, which form part of this invention, are used to provide a further understanding of the invention. The illustrative embodiments of the invention and their descriptions are used to explain the invention and do not constitute an improper limitation of the invention.

[0017] Figure 1 NMR of compound 1A 1 H spectrum;

[0018] Figure 2 NMR of compound 1A 13 C spectrum;

[0019] Figure 3 NMR of compound 1B 1 H spectrum;

[0020] Figure 4 NMR of compound 1B 13 C spectrum;

[0021] Figure 5 : Compound 1C NMR 1 H spectrum;

[0022] Figure 6 : Compound 1C NMR 13 C spectrum;

[0023] Figure 7 NMR of compound 2A 1 H spectrum;

[0024] Figure 8 NMR of compound 2A 13 C spectrum;

[0025] Figure 9 NMR of compound 2B 1 H spectrum;

[0026] Figure 10 NMR of compound 2B 13 C spectrum;

[0027] Figure 11 : Compound 2D NMR 1 H spectrum;

[0028] Figure 12 : Compound 2D NMR 13 C spectrum;

[0029] Figure 13 NMR of compound 3A 1 H spectrum;

[0030] Figure 14 NMR of compound 3A 13 C spectrum;

[0031] Figure 15 : Compound 3E NMR 1 H spectrum;

[0032] Figure 16 : Compound 3E NMR 13 C spectrum;

[0033] Figure 17NMR of compound 4A 1 H spectrum;

[0034] Figure 18 NMR of compound 4A 13 C-spectrum. Detailed Implementation

[0035] The present invention will be further illustrated below with reference to specific embodiments. It should be understood that these embodiments are for illustrative purposes only and are not intended to limit the scope of the invention. Experimental methods in the following embodiments, unless otherwise specified, are generally performed under conventional conditions or as recommended by the manufacturer.

[0036] It should be noted that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to limit the scope of exemplary embodiments according to the invention. As used herein, the singular form is intended to include the plural form as well, unless the context clearly indicates otherwise. Furthermore, it should be understood that when the terms "comprising" and / or "including" are used in this specification, they indicate the presence of features, steps, operations, devices, components, and / or combinations thereof.

[0037] In this invention, "equivalent" (eq) refers to the ratio of the amounts of substances in an interaction. For example, the meaning of donor (1.5 equivalents) and acceptor (1.0 equivalents) is that the molar ratio of the donor compound to the acceptor compound in the reaction is 1.5:1.

[0038] In one or more embodiments of the present invention, a method for constructing α-xylopyranoside bonds with high stereoselectivity is provided, comprising the following steps:

[0039] Using trimethyliodosilane as an activator and triphenylphosphine, diphenylmethylphosphine, or tri(N,N-tetramethylene)phosphonamide as additives, a glycosylation reaction is carried out between a glycosyl donor and a glycosyl acceptor to obtain a glycosylated product.

[0040] The glycosyl donor is an O-glycosyl trichloroacetilimane ester donor with different protecting groups; the protecting group of the glycosyl donor is a protecting group whose neighboring group does not participate in the reaction. Current reports on the synthesis of α-xyloside bonds suffer from various limitations, including low yield, poor stereoselectivity, and limited substrate applicability, making them difficult to apply in practical synthesis. This invention uses protected xyloside trichloroacetilimane esters as glycosyl donors and optimizes a highly α-stereoselective glycosylation method using trimethyliodosilane (TMSI) as an activator and triphenylphosphine oxide (Ph3PO) as an additive by screening the catalytic system, donor / acceptor ratio, additive type, and molecular sieve type. This method features mild reaction conditions, is easy to operate, and achieves highly stereoselective construction of 1,2-cis xylopyranoside bonds without the influence of participating groups, yielding high-yield glycosylated products.

[0041] The protecting groups include benzyl, benzoyl, acetyl, 2-naphthyl, acetylpropionyl, and p-methylphenylthio. Using xylose with full benzyl protection as the glycosyl donor and reacting with different acceptors yields good reactivity. Replacing the protecting group of the glycosyl donor with other protecting groups, such as benzoyl, acetyl, 2-naphthyl, acetylpropionyl, and p-methylphenylthio, and reacting with the corresponding acceptors also yields high stereoselectivity and yield.

[0042] In this context, the other hydroxyl groups of the O-glycosyl trichloroacetylimine ester xylosyl donor or thioglycoside xylosyl donor can be replaced with different protecting groups or linked with other structural units, such as compounds 1-6.

[0043] The glycosyl donors (1-6) are shown below:

[0044]

[0045] The glycosyl receptor includes simple alcohols (isopropanol, tert-butanol, etc.) and compounds with a monohydroxy structure, wherein the compound with a monohydroxy structure is any one of the following compounds A, E:

[0046]

[0047] Specifically, an implementation example includes the following parts:

[0048] Glycosylation reaction between O-glycosyltrichloroacetimide xylosyl donor and monohydroxy acceptor

[0049] The standard operating procedure for the reaction is as follows: Under argon protection, the glycosyl donor (1.5 eq), glycosyl acceptor (1 eq), and triphenylphosphine oxide (Ph3PO) (9 eq) are activated... Molecular sieves (0.15 g / mL) were dissolved in freshly distilled dichloromethane (DCM) (with a final glycosyl acceptor concentration of 0.2 M), stirred at room temperature for 15 min, followed by the addition of trimethyliodosilane (TMSI) (1.5 eq), and stirred at room temperature for 23 h. The reaction was monitored by TLC until completion, and the reaction was quenched with triethylamine (Et3N). The mixture was diluted with DCM and filtered through a diatomaceous earth filter to remove the precipitate. The organic layer was washed with 1 M sodium thiosulfate solution, dried over Na2SO4, filtered, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography to obtain the corresponding glycosylated products.

[0050] In the reaction examples of this glycosylation scheme, the additives can also be diphenylmethylphosphine oxide Ph2(Me)PO or tris(N,N-tetramethylene)phosphonamide, which can also achieve good reaction results.

[0051] In the reaction example of this glycosylation scheme, the reaction solvent is a common organic solvent used in glycosylation reactions. In addition to dichloromethane, other common organic solvents can also be used, including but not limited to chloroform and toluene.

[0052] In the reaction examples of this glycosylation scheme, compounds (1-6) were used as glycosyl donors and various monohydroxy compounds (AH) were used as acceptors, resulting in high coupling yields and high α-stereoselectivity.

[0053] The results of the glycosylation reaction are shown in Table 1:

[0054] Table 1 Glycosylation reactions with different glycosyl donors and glycosyl acceptors

[0055]

[0056] To enable those skilled in the art to better understand the technical solution of the present invention, the technical solution of the present invention will be described in detail below with reference to specific embodiments. It should be noted that the specific embodiments are explanations of the present invention rather than limitations.

[0057] Example 1

[0058] 1. In this Example 1, glycosyl donors 1-5 and glycosyl acceptor AE underwent glycosylation according to the following procedure:

[0059]

[0060] The standard operating procedure was followed: under argon protection, the glycosyl donor (1.5 eq), glycosyl acceptor (1 eq), and triphenylphosphine oxide (Ph3PO) (9 eq) were activated... Molecular sieves (0.15 g / mL) were dissolved in freshly distilled dichloromethane (DCM) (with a final glycosyl acceptor concentration of 0.2 M), stirred at room temperature for 15 min, followed by the addition of trimethyliodosilane (TMSI) (1.5 eq), and stirred at room temperature for 23 h. The reaction was monitored by TLC until completion, and the reaction was quenched with triethylamine (Et3N). The mixture was diluted with DCM and filtered through a diatomaceous earth filter to remove the precipitate. The organic layer was washed with 1 M sodium thiosulfate solution, dried over Na2SO4, filtered, and the solvent was removed by vacuum distillation. The residue was purified by silica gel column chromatography to obtain the corresponding glycosylated products.

[0061] In addition, using diphenylmethylphosphine or tris(N,N-tetramethylene)phosphamide as additives, with other conditions unchanged, the glycosylation reaction between glycosyl donor 1 and glycosyl acceptor A can also yield a better glycosylation reaction.

[0062] 1.1 Glycosylation product 1B

[0063] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 1 (50 mg, 0.089 mmol, 1.5 eq) and glycosyl acceptor B (22 mg, 0.059 mmol, 1 eq) to obtain disaccharide product 1B (38.4 mg, 84%, α:β = 8:1).

[0064] 1 H NMR (600MHz, CDCl3) δ7.43-7.22(m,22H,ArH),7.18-7.12(m,1H,ArH),7.09(m,2H,ArH),6.99-6 .92(m,2H,ArH),5.50(s,1H,PhCH),5.46(d,J=3.8Hz,1H,1b-H),4.94(d,J=10.8Hz,1H,PhCH2), 4.88(d,J=10.8Hz,1H,PhCH2),4.82(d,J=11.8Hz,1H,PhCH2),4.67(d,J=11.8Hz,1H,PhCH2),4. 62(d,J=11.8Hz,1H,PhCH2),4.59(d,J=3.6Hz,1H,1a-H),4.57(d,J=10.7Hz,1H,PhCH2),4.55(d, J=10.2Hz,1H,PhCH2),4.38(m,1H,PhCH2),4.31(t,J=8.7Hz,1H,3a-H),4.23(dd,J=10.3,2.9Hz ,1H,6a”-H),4.02(dd,J=11.1,2.7Hz,1H,5b'-H),3.91(t,J=9.3Hz,1H,3b-H),3.86(m,1H,5a-H) ,3.76(t,J=9.4Hz,1H,4a-H),3.70(dd,J=11.3,2.1Hz,1H,6a'-H),3.64(dd,J=9.5,7.7Hz,1H,2 a-H),3.57(m,1H,5b”-H),3.50(m,1H,4b-H),3.40(s,3H,Me),3.36(dd,J=9.7,3.6Hz,1H,2b-H).

[0065] 13C NMR (151MHz, CDCl3) δ139.05,138.68,137.88,137.58,137.11,129.38,128.72,128.56,128.30,128.15,128.01,127.60,127.56,127.47, 127.42,126.40,102.17,98.76,96.15,83.02,80.78,78.59,78.28,7 7.97,75.66,73.88,73.13,72.56,71.38,69.21,61.90,60.21,55.41.

[0066] 1.2 Glycosylation product 1A

[0067] The standard operating procedure was followed: under argon protection, glycosylation of glycosyl donor 1 (50 mg, 0.089 mmol, 1.5 eq) and glycosyl acceptor A (23 mg, 0.059 mmol, 1 eq) was carried out. With triphenylphosphine oxide (Ph3PO) (9 eq) as an additive, disaccharide product 1A (37.7 mg, 81%, α:β = 14.29:1) was obtained. With diphenylmethylphosphine oxide (Ph2(Me)PO) (9 eq) as an additive, disaccharide product 1A (41.42 mg, 89%, α:β = 12.5:1) was obtained. With tris(N,N-tetramethylene)phosphoramide as an additive, disaccharide product 1A (39.09 mg, 84%, α:β = 8:1) was obtained.

[0068] 1H NMR(400MHz,CDCl3)δ=8.12-8.00(m,2H,ArH),7.48(t,J=7.4Hz,1H,ArH),7.41-7.22(m,7H,ArH),7.19-7.11(m,9H,ArH),7.10-6.99(m,3H,ArH),6.93-6.81(m,4H,ArH),5.41(s,1H,PhCH),5.35(d,J=3.7Hz,1H,1b-H),5.16(dd,J=9.8,3.8Hz,1H,2a-H),5.03(d,J=3.8Hz,1H,1a-H),4.73(d,J=10.8Hz,1H,PhCH2),4.63(d,J=10.9Hz,1H,PhCH2),4.48(t,J=9.6Hz,1H,3a-H),4.45(d,J=12.0Hz,1H,PhCH2),4.35(d,J=11.7Hz,1H,PhCH2),4.27(d,J=12.0Hz,1H,PhCH2),4.23(dd,J=11.4,2.8Hz,1H,5b’-H),4.18(d,J=11.6Hz,1H,PhCH2),3.93-3.87(m,1H,4b-H),3.85(t,J=9.2Hz,1H,4a-H),3.73(m,1H,5b”-H),3.63(t,J=9.2Hz,1H,3b-H),3.55(m,1H,6a’-H),3.36-3.26(m,2H,6a”-H,5a-H),3.33(s,3H,OMe),3.23(dd,J=9.7,3.5Hz,1H,2b-H).

[0069] 13 C NMR(100MHz,CDCl3)δ=165.79,138.94,138.33,137.99,137.03,133.24,130.12,130.08,129.54,129.35,128.50,128.45,128.40,128.31,128.17,128.13,128.08,127.94,127.90,127.50,127.45,127.41,127.36,127.26,127.17,127.13,127.08,126.35,126.31,102.18,97.67,96.57,82.63,80.50,78.54,77.77,75.62,72.70,72.38,71.86,71.43,69.11,61.96,60.33,55.48.

[0070] ESI-HRMS m / z:calcd for C 47 H 52 NO 11 [M+NH4 + ],806.3535;found,806.3562.

[0071] 1.3 Glycosylation product 1C

[0072] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 1 (50 mg, 0.088 mmol, 1.5 eq) and glycosyl acceptor C (28 mg, 0.059 mmol, 1 eq) to obtain disaccharide mixture 1C (45 mg, 88% α:β = 14:1).

[0073] 1 H NMR(600MHz, CDCl3)δ8.11(m,2H,ArH),7.55(m,1H,ArH),7.45-7.18(m,19H, ArH),7.17-7.03(m,6H,ArH),6.94(m,4H,ArH),5.45(s,1H,PhCH),5.36(t,J= 9.4Hz,1H,2a-H),5.34(d,1H,J=3.4Hz,1b-H),4.90(d,J=7.9Hz,1H,1a-H),4. 80(m,1H,PhCH2),4.75(d,J=10.9Hz,1H,PhCH2),4.51(d,J=12.4Hz,1H,PhCH2 ),4.42(m,1H,6a”-H),4.35(m,2H,PhCH2),4.25(t,J=8.8Hz,1H,3a-H),4.14( d,J=11.8Hz,1H,PhCH2),3.88(m,1H,4a-H),3.83-3.76(m,1H,6a'-H),3.71(m ,1H,3b-H),3.62(m,1H,5a-H),3.31(m,1H,5b'-H),3.25(m,1H,4b-H),3.20(d d,J=9.4,3.0Hz,1H,2b-H),3.12(dd,J=10.4,2.9Hz,1H,5b”-H),2.34(s,3H).

[0074] 13C NMR (151MHz, CDCl3) δ165.03,139.04,138.74,138.52,138.04,136.92,135.67,133.97, 133.19,130.08,130.02,129.76,129.47,128.49,128.41,128.29,128.25,128.14,128.0 5,127.85,127.81,127.45,127.42,127.38,127.35,127.32,127.24,126.38,102.10,96.72,81.79,80.38,78.34,77.64,76.08,75.74,72.51,71.52,70.44,68.75,60.36,21.25.

[0075] ESI-HRMS m / z:calcd for C 53 H 52 NaO 10 S[M+Na + ],903.3173;found,903.3195.

[0076] 1.4 Glycosylation product 2B

[0077] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 2 (50 mg, 0.087 mmol, 1.5 eq) and glycosyl acceptor B (22 mg, 0.058 mmol, 1 eq) to obtain disaccharide product 2B (34 mg, 73%, onlyα).

[0078] 1H NMR (400MHz, CDCl3) δ7.46-7.09(m,19H,ArH),6.86(m,2H,ArH),5.49(d,J=3. 7Hz, 1H, 1b-H), 5.46 (t, J = 8.8Hz, 1H, 3b-H), 5.40 (s, 1H, PhCH), 4.83 (d, J = 11. 7Hz,1H,PhCH2),4.63(d,J=11.8Hz,1H,PhCH2),4.57(d,J=3.7Hz,1H,1a-H),4 .54-4.45(m,3H,PhCH2),4.30(t,J=9.3Hz,1H,3a-H),4.21(dd,J=11.2,2.8Hz ,1H,6a”-H),4.16(d,J=12.8Hz,1H,PhCH2),4.02(m,1H,5b”-H),3.84(m,1H,5 a-H),3.70(m,2H,4a-H,6a”-H),3.61(dd,J=9.5,3.7Hz,1H,2a-H),3.55(dd,J =11.4,2.9Hz,1H,5b'-H),3.47-3.40(m,1H,4b-H),3.39(s,3H,Me),3.24(dd, J=10.1,3.5Hz,1H,2b-H),2.70(m,2H,CH2),2.55(m,2H,CH2),2.15(s,3H,Me).

[0079] 13 C NMR (101MHz, CDCl3) δ205.39,170.92,137.32,136.58,136.47,136.09,128.36 ,127.64,127.52,127.39,127.26,127.11,127.05,126.57,126.44,126.41,12 6.26,125.40,101.17,97.78,94.62,81.83,76.91,74.77,74.74,73.01,71.86,71.84,71.44,69.52,68.15,60.85,58.92,54.39,36.92,28.90,28.67,27.14.

[0080] 1.5 Glycosylation product 2A

[0081] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 2 (50 mg, 0.087 mmol, 1.5 eq) and glycosyl acceptor A (23 mg, 0.058 mmol, 1 eq) to obtain disaccharide product 2A (32.9 mg, 71%, onlyα).

[0082] 1 H NMR(400MHz,CDCl3)δ8.20-7.99(m,2H,ArH),7.60-7.46(m,1H,ArH),7.46-7.08(m,14H,ArH),7.02-6.89(m,2H,ArH),6.83(m,2H,ArH),5.44(s,1H,PhCH),5.40(d,J=3.7Hz,1H,1b-H),5.23(t,J=9.6Hz,1H,3b-H),5.15(d,J=3.9Hz,1H,1a-H),5.14(dd,J=10.1,3.9Hz,1H,2a-H),4.50(t,J=9.2Hz,1H,3a-H),4.44(d,J=12.8Hz,1H,PhCH2),4.28(dd,J=11.3,2.6Hz,1H,6a’-H),4.24-4.14(m,2H,PhCH2),4.10(d,J=12.8Hz,1H,PhCH2),3.94(m,1H,5a-H),3.88(t,J=9.3Hz,1H,4a-H),3.78(m,1H,6a”-H),3.64(dd,J=11.4,2.9Hz,1H,5b’-H),3.39(m,3H,Me),3.35(m,1H,5b’-H),3.28(m,1H,4b-H),3.20(dd,J=10.0,3.7Hz,1H,2b-H),2.71-2.53(m,2H,CH2),2.46(m,2H,CH2),2.10(s,3H,Me).

[0083] 13 C NMR(101MHz,CDCl3)δ206.48,171.70,165.64,138.02,137.72,137.08,133.19,130.05,129.57,129.42,128.47,128.43,128.32,128.28,128.16,128.09,128.05,127.51,127.46,127.37,127.16,127.12,126.46,102.31,97.60,96.32,82.35,75.80,75.32,72.69,72.55,72.44,71.91,70.70,69.11,61.94,59.98,55.52,37.87,29.91,28.07.

[0084] ESI-HRMS m / z:calcd for C45 H 52 NO 13 [M+NH4 + ],814.3433;found,814.3457.

[0085] 1.6 Glycosylation product 2D

[0086] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 2 (50 mg, 0.087 mmol, 1.5 eq) and glycosyl acceptor D (30 mg, 0.058 mmol, 1 eq) to obtain disaccharide product 2D (50.8 mg, 95%, only α).

[0087] 1 H NMR (400MHz, CDCl3) δ7.90(m,4H,ArH),7.78(m,2H,ArH),7.44(m,2H,ArH),7.38-7.03(m,18H,ArH),6.14-6.01(t,1H,J=9.2Hz,3a-H),5.36 (t,J=9.6Hz,1H,3b-H),5.30(t,J=9.3Hz,1H,4a-H),5.15(d,J=3.6Hz,1H,1a-H),5.12(dd,J=10.1,3.2Hz,1H,2a-H),4.60(d,J=3.7Hz,1H,1b -H),4.56-4.39(m,4H,4PhCH2),4.27(m,1H,4b-H),3.77-3.69(m,1H,5a-H),3.66(d,J=10.9Hz,1H,5b'-H),3.51(dd,J=11.1,2.8Hz,1H,6a”- H),3.42(m,2H,5b”-H,6a'-H),3.39(s,3H,Me)3.36-3.25(dd,J=10.0,3.7Hz,1H,2b-H),2.63(m,2H,CH2),2.45(m,2H,CH2),2.08(s,3H,Me).

[0088] 13C NMR (101MHz, CDCl3) δ206.46,171.85,165.83,165.76,165.43,138.22,138.13,133.45,133.32,133.04,1 30.11,130.04,130.04,129.95,129.67,129.26,129.12,128.91,128.64,128.62,128.59,128.56,128.53, 128.50,128.46,128.40,128.38,128.36,128.25,128.17,127.81,127.75,127.65,127.61,127.52,96.75,96.62,75.66,73.16,72.86,72.61,72.23,70.54,69.83,68.63,66.76,59.81,55.67,37.94,29.91,28.12.

[0089] 1.7 Glycosylation product 3A

[0090] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 3 (50 mg, 0.087 mmol, 1.5 eq) and glycosyl acceptor A (22 mg, 0.058 mmol, 1 eq) to obtain disaccharide product 3A (35.6 mg, 77%, onlyα).

[0091] 1H NMR(400MHz,CDCl3)δ8.10-8.01(m,2H,ArH),7.92-7.81(m,2H,ArH),7.47(m,2H,ArH),7.38-7.16(m,10H,ArH),7.09-6.93(m,4H,ArH),6.85(m,2H,ArH),6.82-6.75(m,2H,ArH),6.55(m,2H,ArH),5.43(s,1H,PhCH),5.40(t,J=9.6Hz,1H,3b-H),5.37(d,J=3.7Hz,1H,1b-H),5.14(dd,J=9.7,3.8Hz,1H,2a-H),5.08(d,J=3.8Hz,1H,1a-H),4.47(t,J=9.1Hz,1H,3a-H,),4.33(d,J=12.1Hz,1H,PhCH2),4.23(dd,J=11.3,3.3Hz,1H,6a’-H),4.14-4.05(m,2H,PhCH2,),4.05-3.97(m,1H,PhCH2),3.96(m,1H,5a-H),3.81(t,J=9.5Hz,1H,4a-H),3.73(m,1H,6a”-H),3.64(dd,J=11.1,2.3Hz,1H,5b’-H),3.40-3.29(m,2H,4b-H,5b”-H),3.27(s,3H,CH3),3.23(dd,J=10.1,3.6Hz,1H,2b-H).

[0092] 13 C NMR(100MHz,CDCl3)δ164.64,164.38,136.76,136.40,136.12,132.15,131.74,129.30,129.04,128.80,128.58,128.41,127.43,127.24,127.16,127.04,126.92,126.38,126.21,125.48,101.37,96.60,95.29,81.32,74.35,74.01,71.78,71.71,71.45,70.66,69.39,68.11,60.94,58.92,54.50.

[0093] ESI-HRMS m / z:calcd for C 47 H 50 NO 12 [M+NH4 +],820.3328; found,820.3360; calcdfor C 47 H 46 NaO 12 [M+Na + ],825,2881;found,825.2904.

[0094] 1.8 Preparation of glycosylated product 3E

[0095] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 3 (50 mg, 0.087 mmol, 1.5 eq) and glycosyl acceptor E (22 mg, 0.058 mmol, 1 eq) to obtain disaccharide product 3E (35.8 mg, 79%, only α).

[0096] 1 H NMR (400MHz, CDCl3) δ8.09-8.01(m,2H,Ar-H),7.60(m,1H,Ar-H),7.45(m,9H,Ar-H),7.29-7.08(m,14H,Ar-H),5.90(t,J=9.5Hz,1H,3b-H),5.58(s,1 H,PhCH),4.98(d,J=3.4Hz,1H,1b-H),4.91(m,2H,PhCH2),4.87(d,J=3.8Hz,1H,1a-H),4.64-4.55(m,2H,PhCH2),4.50(d,J=12.1Hz,1H,PhCH2),4.43( d, J=12.2Hz, 1H, PhCH2), 4.30 (dd, J=11.1, 3.8Hz, 1H, 6a'-H), 4.14 (t, J=9. 4Hz,1H,3a-H),4.05-3.96(m,1H,5b'-H),3.92(dd,J=9.7,3.8Hz,1H,2a-H) ,3.82(m,1H,5a-H),3.74(m,1H,6a”-H),3.68(dd,J=10.1,3.6Hz,1H,2b-H) ,3.66(t,J=9.5Hz,1H,4a-H),3.60-3.55(m,2H,4b-H,5b”-H),3.44(s,3H).

[0097] 13C NMR (101MHz, CDCl3) δ166.54,166.38,166.09,166.04,165.73,165.65,165.61,165.45,165.32,13 8.14,137.98,137.88,137.45,132.88,130.48,129.81,128.97,128.93,128.88,128.51,128.48,1 28.41,128.35,128.33,128.24,128.20,127.77,127.63,127.58,127.53,127.49,126.03,101.33,97.66,94.57,82.39,82.35,75.95,75.65,75.31,73.59,72.36,72.17,69.10,62.42,60.10,55.31.

[0098] ESI-HRMS m / z:calcd for C 47 H 52 NO 11 [M+NH4 + ],

[0099] 806.3535; found, 806.3561.

[0100] 1.9 Preparation of glycosylated product 4A

[0101] The standard operating procedure was followed: under argon protection, glycosylation reaction was carried out on glycosyl donor 4 (50 mg, 0.079 mmol, 1.5 eq) and glycosyl acceptor A (25 mg, 0.065 mmol, 1 eq) to obtain disaccharide product 4A (47.9 mg, 77%, onlyα).

[0102] 1H NMR(400MHz,CDCl3)δ8.08-8.00(m,2H,ArH),7.50-7.41(m,1H,ArH),7.38-7.23(m,7H,ArH),7.21-7.02(m,7H,ArH),6.94-6.83(m,2H,ArH),6.80-6.67(m,2H,ArH),5.38(s,1H,PhCH),5.33(d,J=3.7Hz,1H,1b-H),5.16(t,J=9.6Hz,1H,3b-H),5.14(dd,J=10.3,4.6Hz,1H,2a-H),5.06(d,J=3.9Hz,1H,1a-H),4.44(t,J=9.2Hz,1H,3a-H),4.37(d,J=12.9Hz,1H,PhCH2),4.21(dd,J=10.8,3.6Hz,1H,6a’-H),4.15-4.05(m,2H,PhCH2),4.02(d,J=12.9Hz,1H,PhCH2),3.92(t,J=9.5Hz,1H,4a-H),3.79(m,1H,5a-H,),3.71(m,1H,6a”-H),3.59(m,1H,5b”-H),3.32(s,3H,CH3),3.30(m,1H,5b-H)3.26-3.17(m,1H,4b-H),3.13(dd,J=10.0,3.8Hz,1H,2b-H),1.86(s,3H).

[0103] 13 C NMR(100MHz,CDCl3)δ168.76,164.63,136.92,136.74,136.08,132.17,129.01,128.55,128.38,127.39,127.25,127.15,127.05,126.50,126.33,126.01,125.43,101.26,96.56,95.34,81.26,74.94,74.33,71.78,71.43,71.11,70.71,69.66,68.07,60.92,58.86,54.48,20.00.

[0104] ESI-HRMS m / z:calcd for C 42 H 44 NaO 12 [M+Na + ],763.2725;found,763.2761.

[0105] The above description is merely a preferred embodiment of the present invention and is not intended to limit the invention. Various modifications and variations can be made to the present invention by those skilled in the art. Any modifications, equivalent substitutions, improvements, etc., made within the spirit and principles of the present invention should be included within the scope of protection of the present invention.

Claims

1. A method for constructing α-xylopyranoside bonds with high stereoselectivity, characterized in that, Includes the following steps: Under argon protection, the glycosyl donor and glycosyl acceptor, as well as triphenylphosphine oxide, diphenylmethylphosphine oxide or tris(N,N-tetramethylene)phosphamide, and the activated molecular sieve were dissolved in dichloromethane and stirred at room temperature for 15 min. Then, trimethyliodosilane was added and stirred at room temperature for 23 h to obtain the glycosylated product. The molar ratio of the glycosyl donor, glycosyl acceptor, trimethyliodosilane, and triphenylphosphine oxide, diphenylmethylphosphine oxide, or tris(N,N-tetramethylene)phosphamide is 1.5:1:1.5:9; the molar ratio of the glycosyl acceptor to the volume ratio of dichloromethane is 0.2 mol / L; and the mass ratio of the molecular sieve to the volume ratio of dichloromethane is 0.15 g / mL. Characterized by the fact that the glycosyl donor is any one of the following compounds 1-5: The glycosyl acceptor is selected from simple alcohols and compounds having a monohydroxyl structure; the simple alcohols include isopropanol and tert-butanol; the compounds having a monohydroxyl structure are any one of the following compounds A, E: 。 2. The method for constructing highly stereoselective α-xylose-pyranoside bonds as described in claim 1, characterized in that, The concentration of the dichloromethane is 0.2 M.

3. The application of the highly stereoselective α-xylopyranoside bond construction method according to claim 1 or 2 in glycosylation reactions, characterized in that, For the highly stereoselective construction of 1,2-cis-xylpyranoside bonds.

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