Process for the glycosylation of a saccharide using elemental iodine as a promoter

Abstract

The application provides a glycosylation reaction method using elemental iodine as a promoter, comprising the following steps: subjecting raw materials comprising a glycosylation donor, a glycosylation acceptor and a promoter to a glycosylation reaction to obtain a glycosylation reaction product; wherein the promoter is elemental iodine; the glycosylation donor has a chemical formula as shown in Formula I: in Formula I, Sugar is a substituted or unsubstituted glycosyl; and the glycosylation acceptor comprises at least one of a compound containing a hydroxyl group, an amide compound, a sulfonamide compound or a pyrimidine compound. The glycosylation reaction method using elemental iodine as a promoter disclosed in the application is low in cost, simple in operation and mild in conditions, and is widely applicable to the synthesis of various oxysaccharides, nitrosaccharides and saccharide drugs.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of chemical synthesis, and particularly relates to a glycosylation reaction method using elemental iodine as a promoter. BACKGROUND

[0002] Important goals of carbohydrate chemistry research include developing new synthetic techniques for polysaccharide and oligosaccharide derivatives, developing new carbohydrate drugs and polysaccharide vaccines, etc. The core topic of synthetic carbohydrate chemistry is the construction of glycosidic bonds, so the general synthetic method of complex carbohydrates is still a challenging goal for synthetic chemists. In the past century, people have been committed to developing new glycosylation methods to efficiently synthesize different glycans and glycoconjugates. However, it is still challenging to find an efficient and universally applicable glycosylation method.

[0003] Since Arthur Michael first reported the glycosylation reaction of sugar-based chloride with alcohol in 1879, sugar-based halides have received extensive attention and in-depth research in the field of carbohydrate chemical synthesis. Many sugar-based halides have been developed for glycosylation reactions. Because of the relatively simple preparation and high reactivity of sugar-based halides, they are still common sugar-based donors in glycosylation reactions. Different types of sugar-based halides (including fluorides, chlorides, bromides and iodides) have different reactivity and preparation methods. Traditional glycosylation reactions require the preparation of sugar-based halides from sugar hemiacetals or various glycosides, which are then activated by activators and further substituted by nucleophiles (such as alcohols or amines) to form corresponding glycosides. Overall, the diversity and high reactivity of sugar-based halides provide a variety of options for the synthesis of carbohydrates. Although there have been significant advances in the application of sugar-based halides in glycosylation reactions, many known glycosylation schemes still need further research and improvement.

[0004] Chinese patent CN 111018927 A proposes an o-(1-phenylvinyl) benzoate glycosylation donor and proposes a glycosylation reaction scheme for the glycosylation donor. However, in the glycosylation reaction mode proposed by it, the reaction is catalyzed by the combination of promoter NIS and Lewis acid TMSOTf. This reaction generates succinimide in the system when a weak nucleophile is used as a glycosylation acceptor, which brings adverse nucleophilic competition and may lead to the generation of one or more by-products, thereby affecting the efficiency and selectivity of the glycosylation reaction; and the glycosylation reaction needs to be carried out at low temperature of 0~ -20℃, the reaction steps are complex, the reaction conditions are relatively harsh, and the overall cost is high. SUMMARY

[0005] The present application provides a method for activating sugar-based o-(1-phenylvinyl) benzoate donor with a single promoter elemental iodine. To solve the problem of complex glycosylation reaction process and high cost in the prior art.

[0006] A glycosylation reaction method using elemental iodine as a promoter, comprising the following steps:

[0007] carrying out a glycosylation reaction on raw materials containing a glycosylation donor, a glycosylation acceptor and a promoter to obtain a glycosylation reaction product;

[0008] wherein the promoter is elemental iodine;

[0009] the chemical formula of the glycosylation donor is shown as formula I:

[0010]

[0011] Sugar in formula I is a substituted or unsubstituted sugar group;

[0012] the glycosylation acceptor includes at least one of a compound containing a hydroxyl group, an amide compound, a sulfonamide compound or a pyrimidine compound.

[0013] Optionally, Sugar has a structural formula as follows:

[0014]

[0015] wherein PG is one or more hydroxyl protecting groups, sugar groups or sugar chains;

[0016] Preferably, the hydroxyl protecting group is selected from any one of a substituted or unsubstituted aroyl group, a substituted or unsubstituted C2-C6 alkanoyl group, a substituted or unsubstituted aryl group, and a substituted or unsubstituted C1-C6 alkyl group.

[0017] Preferably, the hydroxyl protecting group is selected from any one of acetyl (Ac), benzyl (Bn) and benzoyl (Bz).

[0018] A preparation method of the glycosylation donor of formula I, comprising the following steps:

[0019] carrying out an esterification reaction of a compound shown as formula S with 2-(1-phenylvinyl)benzoic acid,

[0020]

[0021] wherein Sugar has the structure as described above.

[0022] The esterification reaction comprises the following steps: dissolving compound S and 2-(1-phenylvinyl)benzoic acid in dichloromethane solvent at room temperature, adding DMAP, EDCI and DIPEA under an inert gas atmosphere, stirring the mixture at room temperature until TLC shows that the reaction is complete, and obtaining the structure of formula I through flash column chromatography.

[0023] The molar ratio of the compound S, 2-(1-phenylvinyl)benzoic acid, DMAP, EDCI and DIPEA is 1:1-1.5:1:1.5-2:3;

[0024] Preferably, the molar ratio is 1:1.2:1:1.8:3; the concentration of the compound S in the dichloromethane solvent is 0.01-1 mol / L, preferably 0.1-0.5 mol / L.

[0025] Optionally, the glycosylation donor is selected from at least one of I-1, I-2, I-3:

[0026]

[0027] Optionally, the glycosylation acceptor is at least one of the compounds of the formulae II-1-12:

[0028]

[0029] Optionally, the molar ratio of the glycosylation donor and the glycosylation acceptor is 1-2.0:1.

[0030] The molar ratio of the glycosylation acceptor and the elemental iodine is 1:1.2-2.5.

[0031] Optionally, the solvent is at least one of an aromatic hydrocarbon solvent, a halogenated hydrocarbon solvent, a ketone solvent, an amide solvent, an ether solvent, a nitrile solvent;

[0032] Preferably, the solvent is at least one of toluene, dichloromethane, diethyl ether, acetone, N,N-dimethylformamide, tetrahydrofuran, acetonitrile;

[0033] Preferably, the solvent is acetonitrile.

[0034] Preferably, the concentration of the glycosylation acceptor in the raw material is 0.033-0.1 mol / L.

[0035] Optionally, the raw material further comprises a drying agent.

[0036] The drying agent is selected from at least one of molecular sieves, molecular sieves, molecular sieves.

[0037] Optionally, the amount of the drying agent added is 2-5 grams per millimole of the glycosylation acceptor.

[0038] Optionally, the reaction temperature for the reaction of the raw material is 0°C- room temperature, and the reaction time is 1.5-24 hours.

[0039] Optionally, the reaction is carried out under an inert atmosphere.

[0040] Optionally, the inert atmosphere is argon or nitrogen.

[0041] Optionally, the method further comprises the following steps:

[0042] After the glycosylation reaction is completed, quenching is carried out to obtain a glycosylation reaction product, and then the glycosylation reaction product is purified.

[0043] Optionally, the glycosylation reaction product is at least one of the compounds shown in P1-P14:

[0044]

[0045] Compared with the prior art, the technical scheme of the present application has the following beneficial effects

[0046] The glycosylation process of the present application only uses elemental iodine as a promoter, does not involve metals, and does not require additional strong acid catalysis, and can be operated under relatively mild conditions (room temperature reaction), and can use sulfonamides as reaction substrates, the substrate range is more extensive than the prior art, and high yield can be obtained.

[0047] The present application can achieve high stereoselectivity of 1,2-cis glycosidic bond construction through mixed solvents, and has a wider application range. And the elemental iodine promoted glycosyl ortho-(1-phenylvinyl) benzoate donor activation method is realized in the synthesis of sugar drug PG545. BRIEF DESCRIPTION OF DRAWINGS

[0048] In order to more clearly illustrate the specific embodiments of the present application or the technical schemes in the prior art, the following will briefly introduce the drawings needed to be used in the specific embodiments or prior art description. Obviously, the drawings in the following description are some embodiments of the present application, and those skilled in the art can also obtain other drawings according to these drawings without creative labor.

[0049] Figure 1 Glycosylation reactions under different conditions. Among them, Trace and Quantitative represent trace reaction and quantitative reaction; 3a yield is the separation yield; the ratio of α:β is determined by NMR. DETAILED DESCRIPTION

[0050] The following detailed description of various example embodiments of the application will not be considered limiting of the application, but rather a description of certain aspects, features, and embodiments of the application. It should be understood that the terminology used herein is for the purpose of describing particular embodiments only and is not intended to be limiting of the application.

[0051] In addition, for numerical ranges of values recited herein, it is contemplated that each intervening value, to the tenth of the unit of the lower limit unless the context clearly dictates otherwise, between the upper and lower limits of that range is also specifically contemplated. Each smaller range that fails within the interval of that range and each value

[0052] As used herein, the terms "comprises," "comprising," "includes," "including," "has," "having," "contains," "containing," or variations thereof, are intended to be open-ended terms that mean including, but not limited to.

[0053] The starting materials, reagents, and other materials used in the examples below are commercially available unless otherwise indicated. Unless otherwise indicated, all technical and scientific terms used herein have the same meaning as is commonly understood by one of ordinary skill in the art to which this application belongs. Although methods and materials similar or equivalent to those described herein can be used in the practice or testing of the present application, preferred methods and materials are described. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety.

[0054] The present application provides a glycosylation reaction method using elemental iodine as a promoter, which comprises the following steps:

[0055] Subjecting a raw material comprising a glycosylation donor, a glycosylation acceptor, and a promoter to a glycosylation reaction to obtain a glycosylation reaction product;

[0056] The promoter is elemental iodine.

[0057] The glycosylation donor has a chemical formula as shown in Formula I:

[0058]

[0059] In Formula I, Sugar is a substituted or unsubstituted sugar group.

[0060] The glycosylation acceptor comprises at least one of a compound containing a hydroxyl group, an amide compound, a sulfonamide compound, or a pyrimidine compound.

[0061] All compounds in Formula I used in the examples are prepared according to the method described in Chinese Patent CN 111018927 A, and the specific preparation process is as follows:

[0062]

[0063] wherein Sugar is a substituted or unsubstituted sugar group. Compound S-1 (1.0 eq.) and 2-(1-phenylvinyl)benzoic acid (1.2 eq.) were dissolved in anhydrous DCM (c = 0.1 M), 4-dimethylaminopyridine (DMAP) (1.0 eq.), N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDCI) (1.8 eq.) and N,N-diisopropylethylamine (DIPEA) (3.0 eq.) were added. The mixture was stirred at room temperature until TLC analysis indicated completion of the reaction. Then, the mixture was directly purified by silica gel flash column chromatography to give the glycosylated donor of Formula I.

[0064] Compound I-1 was prepared according to the procedure of Route one from the corresponding starting material S-1 (400 mg, 0.74 mmol) for I-1. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10:1) to give I-2 (532 mg, 96%, a:β = 1 :3.5) as a colorless syrup.1H NMR (400 MHz, CDCI3) δ 7.96 (dd, J = 7.9, 1.4 Hz, 3.5H), 7.90 (dd, J = 7.8, 1.4 Hz, 1H), 7.59 - 7.32 (m, 21H), 7.30 - 7.15 (m, 106H), 6.40 (d, J = 3.4 Hz, 1H), 5.69 (d, J = 3.4 Hz, 4.5H), 5.63 (d, J = 8.0 Hz, 3.5H), 5.30 (s, 1H), 5.16 (d, J = 8.1 Hz, 4.5H), 4.87 - 4.74 (m, 13H), 4.66 - 4.40 (m, 26H), 3.76 - 3.43 (m, 30H).

[0065] The structure of compound I-1 is as follows:

[0066]

[0067] Compound 1-2 was prepared according to the procedure of Route one from the corresponding starting material S-2 (200 mg, 0.36 mmol) for 1-2. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 5: 1) to give 1-1 (265 mg, 97%, a: β = 1 : 8.5) as a colorless syrup. β configuration: ¾ NMR (400 MHz, CDC13) δ 7.95 - 7.85 (m, 3H), 7.53 (t, J = 7.4 Hz, 1H), 7.49 - 7.43 (m, 1H), 7.41 - 7.05 (m, 24H), 5.78 (d, J = 8.2 Hz, 1H), 5.57 (s, 1H), 5.00 (s, 1H), 4.80 (d, J = 10.8 Hz, 1H), 4.73 (d, J = 11.2 Hz, 1H), 4.67 - 4.56 (m, 3H), 4.47 (d, J = 12.1 Hz, 1H), 3.90 (t, J = 9.2 Hz, 1H), 3.83 (t, J = 9.0 Hz, 1H), 3.75 (dd, J = 11.1, 3.5 Hz, 1H), 3.68 (dd, J = 11.1, 2.0 Hz, 1H), 3.61 (dt, J = 9.6, 2.7 Hz, 1H).

[0068] The structure of compound 1-2 is as follows:

[0069]

[0070] Compound 1-3 was prepared according to the procedure of Route one from the corresponding starting material S-3 (500 mg, 0.92 mmol) for 1-3. The crude product was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 10: 1) to give 1-3 (658 mg, 95%, a: β = 1 : 3.3) as a colorless syrup. β configuration: ¾ NMR (600 MHz, CDC13) δ 7.94 (d, J = 7.8 Hz, 1H), 7.54 (t, J = 7.5 Hz, 1H), 7.38 (t, J = 7.7 Hz, 1H), 7.36 - 7.27 (m, 14H), 7.25 - 7.10 (m, 12H), 5.66 (d, J = 1.0 Hz, 1H), 5.58 (d, J = 8.0 Hz, 1H, H-1), 5.13 (d, J = 1.0 Hz, 1H), 4.94 (d, J = 11.4 Hz, 1H), 4.72 - 4.66 (m, 3H), 4.61 (dd, J = 11.2, 9.4 Hz, 2H), 4.41 (d, J = 11.8 Hz, 1H), 4.38 (d, J = 11.7 Hz, 1H), 3.97 - 3.92 (m, 2H), 3.65 - 3.55 (m, 3H), 3.47 (dd, J = 9.0, 4.9 Hz, 1H).

[0071] The structure of compound I-3 is as follows:

[0072]

[0073] Example 2:

[0074] Some of the compounds in formula P of the present application are prepared according to the following routes:

[0075]

[0076] wherein NuH is at least one of any hydroxyl-containing compound, pyrimidine compound, amide compound, sulfonamide compound. The specific steps are as follows:

[0077] The glycosylation donor of formula I (1.5 equivalents) and the acceptor of formula II (1.0 equivalent) are dissolved in anhydrous MeCN (c = 0.033 M) at room temperature, and dry MS (3.0 g / mmol) is stirred at room temperature for 10 minutes. Then iodine (2.0 equivalents) is added thereto, and the reaction mixture is stirred at room temperature (25°C) for 1.5-24 hours. Then Et3N is added to quench the reaction, and direct purification by silica gel column chromatography to obtain the glycosylation product of formula P.

[0078] 2-1 Preparation of glycosylation product P1:

[0079]

[0080] According to the general method of Route two, glycosylation of I-1 (43.4 mg, 0.06 mmol) with II-1 (18 mg, 0.04 mmol) was carried out for 2 h to give P1 (38 mg, 99%, a:β = 1 :4) as a syrup:1H NMR (400 MHz, CDC13) δ 7.34 - 7.22 (m, 37H), 7.17 (ddd, J = 9.8, 5.6, 2.6 Hz, 6.5H), 7.11 (dd, J = 7.1, 2.5 Hz, 0.5H), 4.96 (dd, J = 10.9, 3.8 Hz, 2.5H), 4.93 - 4.87 (m, 1.5H), 4.83 - 4.68 (m, 7H), 4.66 - 4.56 (m, 4H), 4.55 - 4.48 (m, 3.5H), 4.44 (d, J = 12.1 Hz, 0.5H), 4.34 (d, J = 7.7 Hz, 1H), 4.17 (dd, J = 10.8, 2.0 Hz, 1H), 3.97 (dt, J = 14.7, 9.5 Hz, 1.5H), 3.85 - 3.80 (m, 1H), 3.77 - 3.48 (m, 10H), 3.47 - 3.40 (m, 1.5H), 3.34 (s, 0.75H), 3.32 (s, 3H).

[0081] 2-2 Preparation of glycosylation product P2:

[0082]

[0083] According to the general method of Route two, glycosylation of I-1 (50 mg, 0.07 mmol) with II-8 (17.4 mg, 0.13 mmol) was carried out for 16 h to give P2 (35 mg, 80%, β:α >10:1) as a syrup:1H NMR (600 MHz, CDC13) δ 8.90 (s, 1H), 7.38-7.26 (m, 16H), 7.18 (d, J = 7.2 Hz, 4H), 6.76 (d, J = 5.6 Hz, 1H), 5.55 (d, J = 9.1 Hz, 1H, H-1), 4.94 (s, 2H), 4.82 (dd, J = 16.5, 11.4 Hz, 2H), 4.58 (d, J = 10.8 Hz, 1H), 4.53-4.45 (m, 3H), 3.86 (t, J = 9.0 Hz, 1H), 3.70-3.58 (m, 4H), 3.38 (t, J = 9.0 Hz, 1H);13C NMR (151 MHz, CDC13) δ 156.6, 156.4, 149.0, 140.8, 139.2, 138.1, 137.8, 137.7, 137.0, 129.0, 129.0, 128.8, 128.7, 128.7, 128.6, 128.6, 128.3, 128.1, 128.1, 128.0, 127.9, 127.8, 86.0, 81.7 (C-1β), 77.8, 77.6, 77.3, 76.1, 75.3, 74.6, 73.6, 68.3.

[0084] 2-3 Preparation of glycosylation product P3:

[0085]

[0086] According to the general method of Route two, glycosylation of I-1 (60 mg, 0.08 mmol) with II-9 (6.9 mg, 0.04 mmol) was carried out for 24 h to give P3 (13.5 mg, 48%, a:β = 1 :5) as a syrup:1H NMR (600 MHz, CDC13): δ 7.76 (d, J = 7.9 Hz, 2H), 7.36-7.27 (m, 19H), 7.25-7.20 (m, 3H), 7.18-7.09 (m, 5H), 4.97 (d, J = 9.9 Hz, 1H), 3.67 (t, J = 8.9 Hz, 1H), 3.60-3.56 (m, 2H), 3.36-3.27 (m, 3H), 2.35 (s, 0.6H, CH3a), 2.34 (s, 3H, CH3P);13C NMR (151 MHz, CDC13) δ 143.5, 138.6, 138.4, 138.1, 138.0, 137.6, 129.6, 129.5, 128.7, 128.7, 128.7, 128.6, 128.5, 128.3, 128.2, 128.0, 128.0, 128.0, 128.0, 127.9, 127.9, 127.9, 127.7, 127.4, 85.7, 84.4, 82.1, 80.5 (C-1P), 76.5, 75.9, 75.1, 75.0, 73.7, 68.3, 29.9 (CH3a), 21.6 (CH3P).

[0087] 2-4 Preparation of glycosylation product P4:

[0088]

[0089] According to the general method of Route two, glycosylation of I-2 (59.0 mg, 0.08 mmol) with II-1 (18.0 mg, 0.04 mmol) was carried out for 2 h to give P (35.0 mg, 90%) as a syrup:1H NMR (400 MHz, CDC13) δ 7.89 - 7.80 (m, 2H), 7.39 - 7.33 (m, 1H), 7.25 - 7.03 (m, 30H), 6.96 - 6.91 (m, 2H), 5.27 (dd, J = 9.4, 8.0 Hz, 1H), 4.79 (d, J = 11.0 Hz, 1H), 4.73 (d, J = 10.8 Hz, 1H), 4.65 (dd, J = 11.6, 4.4 Hz, 2H), 4.61 - 4.54 (m, 2H), 4.53 - 4.44 (m, 5H), 4.39 (d, J = 3.5 Hz, 1H), 4.36 (d, J = 11.1 Hz, 1H), 4.20 (d, J = 11.0 Hz, 1H), 4.08 - 4.03 (m, 1H), 3.82 - 3.56 (m, 7H), 3.48 (ddd, J = 9.7, 5.2, 2.0 Hz, 1H), 3.35 (dd, J = 9.6, 3.6 Hz, 1H), 3.29 (t, J = 9.3 Hz, 1H), 3.11 (s, 3H).

[0090] 2-5 Preparation of glycosylation product P5:

[0091]

[0092] According to the general method of Route two, glycosylation of I-3 (50 mg, 0.07 mmol) with II-2 (23.2 mg, 0.05 mmol) was carried out for 2 h to give P5 (43 mg, 95%, β only) as a syrup:1H NMR (600 MHz, CDC13): δ 8.03 (dd, 2H), 7.87 (dd, 2H), 7.83 (dd, 2H), 7.56-7.50 (m, 3H), 7.36 (q, J = 8.2 Hz, 4H), 7.32-7.26 (m, 13H), 7.20 (t, J = 7.1 Hz, 1H), 7.11-7.07 (m, 2H), 7.07-7.03 (m, 1H), 5.75 (dd, J = 6.5, 4.8 Hz, 1H), 5.72 (d, J = 1.8 Hz, 1H, H-1), 5.70-5.66 (m, 1H), 4.98 (d, J = 10.9 Hz, 1H), 4.78 (d, J = 10.9 Hz, 1H), 4.72 (d, J = 12.2 Hz, 1H), 4.61-4.55 (m, 5H), 4.47-4.41 (m, 2H), 3.93 (t, J = 9.2 Hz, 1H), 3.84 (t, J = 9.4 Hz, 1H), 3.78 (dd, J = 10.7, 4.5 Hz, 1H), 3.70-3.65 (m, 2H), 3.52 (dd, J = 9.6, 3.4 Hz, 1H), 3.35 (s, 3H);13C NMR (151 MHz, CDC13) δ 166.2, 165.4, 165.1, 138.5, 138.4, 138.1, 133.5, 133.3, 129.9, 129.7, 129.3, 129.1, 128.6, 128.5, 128.4, 128.3, 128.1, 127.8, 127.7, 127.5, 107.3 (C-1), 98.0, 81.2, 80.1, 78.7, 77.6, 75.9, 75.7, 73.5, 73.4, 72.1, 69.6, 68.7, 64.8, 55.4, 29.9.

[0093] 2-6 Preparation of glycosylation product P6:

[0094]

[0095] According to the general method of Route two, glycosylation of I-3 (50 mg, 0.07 mmol) with II-3 (24 mg, 0.05 mmol) was carried out for 2 h to give P6 (45 mg, 97%, β only) as a syrup:1H NMR (600 MHz, CDC13): δ 7.98 (t, J = 7.7 Hz, 4H), 7.88 (d, J = 8.0 Hz, 2H), 7.58-7.54 (m, 1H), 7.52-7.46 (m, 2H), 7.42-7.39 (m, 4H), 7.34-7.21 (m, 14H), 7.16-7.11 (m, 3H), 5.79 (dd, J = 7.1, 4.8 Hz, 1H), 5.72 (d, J = 4.8 Hz, 1H), 5.44 (s, 1H), 5.02 (d, J = 2.6 Hz, 1H), 4.98 (d, J = 10.8 Hz, 1H), 4.84 (d, J = 10.8 Hz, 1H), 4.80 (d, J = 10.8 Hz, 1H), 4.70 (q, J = 5.9 Hz, 1H), 4.63 (d, J = 12.1 Hz, 1H), 4.56-4.46 (m, 4H), 4.02-3.95 (m, 2H), 3.79 (ddd, J = 10.1, 3.8, 2.0 Hz, 1H), 3.74 (dd, J = 10.6, 3.8 Hz, 1H), 3.69-3.64 (m, 2H), 3.45 (s, 3H);13C NMR (151 MHz, CDC13) δ 166.1, 165.3, 165.3, 138.6, 138.3, 138.1, 133.6, 133.4, 133.1, 129.9, 129.9, 129.8, 129.7, 129.3, 129.1, 128.6, 128.5, 128.5, 128.5, 128.4, 128.2, 128.0, 128.0, 127.8, 127.8, 127.7, 103.9 (C-1), 97.2, 80.9, 78.8, 77.9, 76.8, 76.0, 75.8, 75.2, 73.6, 72.8, 70.3, 68.6, 65.4, 55.3.

[0096] 2-7 Preparation of glycosylation product P7:

[0097]

[0098] According to the general method of Route two, glycosylation of I-3 (50 mg, 0.07 mmol) with II-4 (7.8 mg, 0.05 mmol) was carried out for 2 h to give P7 (29.7 mg, 99%, β only) as a syrup:1H NMR (600 MHz, CDC13): δ 8.07 (d, J = 6.8 Hz, 2H), 8.02 (d, J = 6.8 Hz, 2H), 7.90 (d, J = 6.8 Hz, 2H), 7.60-7.55 (m, 1H), 7.54-7.49 (m, 2H), 7.42 (t, J = 7.8 Hz, 2H), 7.38 (t, J = 7.7 Hz, 2H), 7.33 (t, J = 7.8 Hz, 2H), 5.85 (dd, J = 6.6, 4.8 Hz, 1H), 5.62 (dd, J = 4.7, 1.1 Hz, 1H), 5.34 (d, J = 1.1 Hz, 1H, H-1), 4.74-4.67 (m, 2H), 4.55 (dd, J = 11.3, 5.2 Hz, 1H), 3.38 (td, J = 10.7, 4.3 Hz, 1H), 2.22-2.15 (m, 2H), 1.63-1.58 (m, 2H), 1.37-1.31 (m, 1H), 1.22-1.16 (m, 1H), 1.02-0.92 (m, 2H), 0.90 (d, J = 7.0 Hz, 3H), 0.88-0.82 (m, 1H), 0.81 (d, J = 6.6 Hz, 3H), 0.79 (d, J = 6.9 Hz, 3H), 0.78-0.72 (m, 1H);13C NMR (151 MHz, CDC13) δ 166.3, 165.6, 165.5, 133.5, 133.5, 133.2, 130.0, 129.9, 129.9, 129.9, 129.5, 129.2, 128.6, 128.5, 128.4, 107.1 (C-1), 82.0, 78.6, 76.1, 72.8, 65.2, 48.3, 43.0, 34.4, 31.7, 25.8, 23.4, 22.3, 21.1, 16.3.

[0099] 2-8 Preparation of glycosylation product P8:

[0100]

[0101] According to the general procedure of route two, glycosylation of I-3 (50 mg, 0.07 mmol) with II-5 (19.4 mg, 0.05 mmol) was carried out for 2 h to give P8 (41 mg, 99%, β only) as a colorless syrup:1H NMR (600 MHz, CDC13): δ 8.07 (d, J = 7.7 Hz, 2H), 8.02 (d, J = 7.7 Hz, 2H), 7.89 (d, J = 7.8 Hz, 2H), 7.57 (t, J = 7.5 Hz, 1H), 7.54-7.48 (m, 2H), 7.42 (t, J = 7.7 Hz, 2H), 7.37 (t, J = 7.7 Hz, 2H), 7.32 (t, J = 7.7 Hz, 2H), 5.88 (dd, J = 7.0, 4.8 Hz, 1H), 5.63 (d, J = 4.7 Hz, 1H), 5.41 (s, 1H, H-1), 4.73 (dd, J = 11.5, 4.3 Hz, 1H), 4.69 (dt, J = 6.9, 4.8 Hz, 1H), 4.52 (dd, J = 11.5, 5.1 Hz, 1H), 3.65-3.58 (m, 1H), 1.95 (dt, J = 12.7, 3.4 Hz, 1H), 1.92-1.87 (m, 1H), 1.85-1.77 (m, 1H), 1.70 (dt, J = 13.4, 3.7 Hz, 1H), 1.62 (dt, J = 12.8, 3.9 Hz, 1H), 1.57-1.50 (m, 3H), 1.49-1.44 (m, 1H), 1.42-1.21 (m, 9H), 1.16-0.95 (m, 11H), 0.92-0.85 (m, 10H), 0.84-0.79 (m, 1H), 0.74 (s, 3H), 0.64 (s, 3H), 0.58 (ddd, J = 14.0, 10.6, 4.0 Hz, 1H);13C NMR (151 MHz, CDC13) δ 166.3, 165.5, 133.5, 133.4, 133.2, 130.0, 129.9, 129.5, 129.2, 128.6, 128.5, 128.4, 103.9 (C-1), 78.6, 77.8, 76.3, 72.8, 65.1, 56.6, 56.4, 54.5, 45.0, 42.7, 40.2, 39.7, 37.0, 36.3, 36.1, 35.9, 35.7, 35.6, 32.2, 28.8, 28.4, 28.2, 27.8, 24.4, 24.0, 23.0, 22.7, 21.4, 18.8, 12.4, 12.2.

[0102] Example 3:

[0103] Some of the compounds in formula P of this invention were prepared according to the following route three:

[0104]

[0105] Wherein, NuH can be any compound containing a hydroxyl group, or a pyrimidine compound, or an amide compound.

[0106] The specific steps are as follows:

[0107] At room temperature, the glycosylated donor of formula I-1 (1.5 equivalents) was dissolved in a dry DCM / DMF mixed solvent (0.033 M, v / v 15:1), and then, under an inert gas atmosphere, dry [unclear - possibly a specific solvent or product] was added. MS (3.0 g / mmol) was stirred at room temperature for 10 minutes. Iodine I2 (2.0 equivalents) was added at 0°C and stirred for 1 hour until TLC analysis showed complete activation of the donor. Then, the acceptor of formula II (1.0 equivalent) was added to the reaction system, and the mixture was slowly heated to room temperature and stirred for 1.5–24 hours until TLC showed complete acceptor conversion. The reaction was then quenched with Et3N, and the product was purified directly by silica gel column chromatography to obtain the glycosylated product represented by formula P.

[0108] 3-1 Preparation of glycosylated product P9:

[0109]

[0110] Glycosylation of I-1 (43.4 mg, 0.06 mmol) with II-3 (18 mg, 0.04 mmol) according to the general procedure of Scheme three afforded P9 (34.5 mg, 90%, a: ß > 20: 1) as a colorless syrup: ¾ NMR (600 MHz, CDC13): d 7.30 (d, J = 6.9 Hz, 2H), 7.27-7.15 (m, 27H), 7.08-7.01 (m, 4H), 6.93 (t, J = 7.5 Hz, 2H), 4.91 (d, J = 10.8 Hz, 1H), 4.87 (dd, J = 10.9, 3.5 Hz, 2H), 4.84 (d, J = 10.3 Hz, 1H), 4.78-4.71 (m, 4H), 4.69 (d, J = 10.4 Hz, 1H), 4.64 (d, J = 12.2 Hz, 1H), 4.54 (d, J = 12.1 Hz, 1H), 4.48 (d, J = 12.1 Hz, 1H), 4.45-4.39 (m, 2H), 4.36 (d, J = 11.0 Hz, 1H), 4.25 (d, J = 12.1 Hz, 1H), 4.02 (d, J = 9.4 Hz, 1H), 3.99 (d, J = 9.5 Hz, 1H), 3.93 (dt, J = 10.2, 2.5 Hz, 1H), 3.77 (dd, J = 9.9, 3.4 Hz, 1H), 3.71 (dt, J = 10.1, 3.9, 2.1 Hz, 1H), 3.67-3.58 (m, 3H), 3.55 (t, J = 9.5 Hz, 1H), 3.51 (dd, J = 9.6, 3.6 Hz, 1H), 3.46 (dd, J = 10.9, 2.9 Hz, 1H), 3.41-3.38 (m, 1H), 3.38 (s, 3H);13C NMR (151 MHz, CDC13) d 138.9, 138.9, 138.6, 138.5, 138.3, 138.1, 138.1, 128.6, 128.5, 128.5, 128.5, 128.4, 128.4, 128.3, 128.2, 128.1, 128.0, 128.0, 127.8, 127.8, 127.7, 127.7, 127.7, 127.6, 127.5, 96.5 (C-1), 94.3 (C-1'), 82.3, 80.9, 79.2, 78.2, 77.8, 76.3, 75.8, 75.1, 75.0, 74.9, 73.7, 73.5, 73.0, 70.4, 70.3, 68.7, 68.3, 55.0.

[0111] 3-2 Preparation of glycosylation product P10:

[0112]

[0113] Glycosylation of I-1 (43 mg, 0.06 mmol) with II-6 (10 mg, 0.04 mmol) according to the general procedure of Route three gave P10 (29.5 mg, 98%, a:β > 20:1) as a colorless syrup:1H NMR (600 MHz, CDC13): δ 7.35-7.26 (m, 18H), 7.12 (d, J = 7.3 Hz, 2H), 5.87 (d, J = 3.5 Hz, 1H, H-1'), 5.24 (d, J = 3.5 Hz, 1H, H-1), 4.96 (d, J = 10.9 Hz, 1H), 4.82 (d, J = 10.6 Hz, 1H), 4.80 (d, J = 10.8 Hz, 1H), 4.74 (d, J = 11.8 Hz, 1H), 4.69 (d, J = 11.8 Hz, 1H), 4.66 (d, J = 3.6 Hz, 1H), 4.60 (d, J = 12.1 Hz, 1H), 4.51-4.41 (m, 3H), 4.22 (d, J = 2.8 Hz, 1H), 4.12 (dd, J = 8.1, 2.7 Hz, 1H), 4.07-4.01 (m, 2H), 3.93 (t, J = 9.4 Hz, 1H), 3.79 (dt, J = 10.2, 3.1 Hz, 1H), 3.73-3.66 (m, 2H), 3.60 (t, J = 9.5 Hz, 1H), 3.55 (dd, J = 9.8, 3.6 Hz, 1H), 1.47 (s, 3H), 1.40 (s, 3H), 1.25 (s, 3H), 1.22 (s, 3H);13C NMR (151 MHz, CDC13) δ 138.8, 138.3, 138.1, 138.0, 128.6, 128.5, 128.5, 128.2, 128.1, 128.0, 128.0, 127.9, 127.8, 127.7, 127.7, 111.9, 109.2, 105.3 (C-1'), 98.1 (C-1), 83.8, 81.7, 81.3, 80.9, 80.1, 77.9, 75.8, 75.4, 73.7, 73.2, 72.5, 71.4, 68.8, 67.2, 27.1, 26.9, 26.3, 25.6.

[0114] 3-3 Preparation of glycosylation product P11:

[0115]

[0116] According to the general method of Scheme three, glycosylation of I-1 (44 mg, 0.06 mmol) with II-7 (20 mg, 0.04 mmol) gave P11 (35.6 mg, 87%, a:β >20:1) as a white solid: 1H NMR (600 MHz, CDC13): δ 8.04 (d, J = 7.2 Hz, 2H), 7.95 (d, J = 7.5 Hz, 2H), 7.93 (d, J = 7.7 Hz, 2H), 7.59 (d, J = 7.5 Hz, 2H), 7.39-7.25 (m, 23H), 7.12 (d, J = 7.6 Hz, 2H), 7.09 (d, J = 5.7 Hz, 2H), 5.70 (dd, J = 10.9, 3.0 Hz, 1H), 5.62 (dd, J = 10.9, 3.6 Hz, 1H), 5.24 (d, J = 3.7 Hz, 1H, H-1'), 5.03 (d, J = 11.0 Hz, 1H), 4.93 (d, J = 10.9 Hz, 1H), 4.91 (d, J = 3.5 Hz, 1H, H-1), 4.81 (d, J = 11.8 Hz, 1H), 4.78 (d, J = 11.0 Hz, 1H), 4.74-4.67 (m, 3H), 4.47-4.45 (m, 1H), 4.40-4.32 (m, 3H), 4.15-4.11 (m, 1H), 4.08 (dt, J = 10.1, 2.1 Hz, 1H), 4.05-4.04 (m, 1H), 3.70 (t, J = 9.6 Hz, 1H), 3.55 (dd, J = 9.9, 3.5 Hz, 1H), 3.41 (s, 3H), 3.24 (dd, J = 11.0, 2.3 Hz, 1H), 2.85 (dd, J = 11.0, 2.0 Hz, 1H);13C NMR (151 MHz, CDC13) δ 166.3, 166.2, 166.0, 139.0, 138.6, 138.0, 133.3, 133.3, 130.1, 129.9, 129.8, 128.6, 128.5, 128.5, 128.4, 128.4, 128.3, 128.1, 128.0, 127.9, 127.9, 127.7, 127.6, 127.6, 100.3 (C-1), 97.5 (C-1'), 82.0, 79.8, 77.8, 76.7, 75.7, 75.0, 74.3, 73.5, 71.4, 70.6, 69.4, 68.5, 67.9, 63.1, 55.5.

[0117] 3-4 Preparation of glycosylation product P12:

[0118]

[0119] According to the general method of Scheme three, glycosylation of I-1 (39 mg, 0.05 mmol) with II-10 (23 mg, 0.03 mmol) gave P12 (34.5 mg, 83%, a: ß > 20: 1) as colorless syrup: ¾ NMR (600 MHz, CDC13): d 7.94 (d, J = 7.9 Hz, 1H), 7.55 (d, J = 8.2 Hz, 1H), 7.39 (t, J = 7.4 Hz, 2H), 7.33 (d, J = 7.5 Hz, 1H), 7.26 - 7.15 (m, 35H), 7.11 - 7.05 (m, 4H), 5.71 - 5.67 (m, 2H, H-1 and CCHH), 5.62 (d, J = 3.6 Hz, 1H, H-1'), 5.15 (s, 1H), 4.86 (d, J = 10.8 Hz, 1H), 4.82 - 4.72 (m, 4H), 4.58 (d, J = 11.9 Hz, 1H), 4.55 - 4.41 (m, 7H), 4.27 (d, J = 12.1 Hz, 1H), 4.17 (t, J = 9.1 Hz, 1H), 3.90 (t, J = 9.4 Hz, 1H), 3.84 (dd, J = 11.4, 3.3 Hz, 1H), 3.80 (t, J = 8.5 Hz, 1H), 3.76 (dt, J = 10.1, 2.5 Hz, 1H), 3.64 (dt, J = 8.9, 3.8 Hz, 3H), 3.59 (t, J = 8.0 Hz, 1H), 3.53 - 3.46 (m, 2H), 3.37 (d, J = 9.7 Hz, 1H);13C NMR (151 MHz, CDC13) d 165.2, 149.1, 143.8, 140.6, 138.9, 138.7, 138.6, 138.6, 138.15, 138.1, 137.9, 132.3, 131.7, 130.6, 129.8, 128.4, 128.4, 128.3, 128.3, 128.1, 128.0, 127.9, 127.8, 127.8, 127.8, 127.7, 127.7, 127.6, 127.5, 127.3, 126.9, 126.8, 114.5, 97.0 (C-1'), 94.5 (C-1), 84.9, 82.1, 80.7, 79.6, 77.8, 75.6, 75.5, 75.1, 74.5, 74.0, 73.6, 73.5, 73.4, 72.5, 71.1, 68.8, 68.4.

[0120] Example 4:

[0121] The preparation route of Formula P13 of the present application is as follows:

[0122]

[0123] wherein OPTFAI is N-phenyltrifluoroacetimidate; OPVB is o-(l-phenylethenyl)benzoate; and OMP is p-methoxyphenyl ether.

[0124] The specific steps are as follows:

[0125] The donor S4 (50 mg, 0.07 mmol) was dissolved in dry DCM / DMF (1.4 mL, v / v 15:1) and fresh flame-dried 4A molecular sieves were added The reaction solution was cooled to 0 °C and then TfOH (8.3 μL, 0.09 mmol) was added. After 30 min, acceptor II-10 (30.8 mg, 0.05 mmol) was added and the reaction was stirred at 0 °C until thin layer chromatographic analysis indicated complete conversion of the acceptor. Then acceptor II-12 (26 mg, 0.05 mmol) and iodine (18 mg, 0.07 mmol) were added to the reaction. The resulting mixture was stirred at 0 °C to room temperature until thin layer chromatographic analysis indicated completion of the reaction. The solution was diluted with dichloromethane and quenched with saturated sodium thiosulfate. The organic phase was washed with water and brine, dried over anhydrous sodium sulfate, filtered under vacuum and concentrated.P13 (57.5 mg, 81%) as colorless syrup: 1H NMR (600 MHz, CDC13): δ 7.26-7.06 (m, 50H), 7.04 (d, J = 8.7 Hz, 2H), 6.81 (d, J = 8.8 Hz, 2H), 5.64 (d, J = 3.6 Hz, 1H), 5.56 (d, J = 3.7 Hz, 1H), 5.02 (d, J = 10.9 Hz, 1H), 4.96 (d, J = 11.6 Hz, 1H), 4.92 (d, J = 7.6 Hz, 1H), 4.89 (d, J = 11.5 Hz, 1H), 4.85 (d, J = 10.9 Hz, 1H), 4.82 (d, J = 11.6 Hz, 1H), 4.80-4.77 (m, 2H), 4.76 (d, J = 10.9 Hz, 1H), 4.73 (d, J = 11.0 Hz, 1H), 4.56-4.50 (m, 5H), 4.47-4.42 (m, 5H), 4.29 (d, J = 12.1 Hz, 1H), 4.10 (d, J = 9.0 Hz, 1H), 4.06-4.00 (m, 2H), 3.94-3.90 (m, 2H), 3.86-3.83 (m, 2H), 3.77 (s, 3H), 3.77-3.72 (m, 3H), 3.70-3.64 (m, 3H), 3.57-3.52 (m, 3H), 3.49 (dd, J = 9.9, 3.6 Hz, 1H), 3.41 (d, J = 10.6 Hz, 1H);13C NMR (151 MHz, CDC13) δ 155.5, 151.6, 139.0, 138.9, 138.6, 138.4, 138.3, 138.3, 138.1, 137.9, 128.5, 128.4, 128.4, 128.4, 128.4, 128.4, 128.3, 128.3, 128.1, 128.0, 127.9, 127.8, 127.8, 127.7, 127.6, 127.6, 127.5, 127.5, 127.3, 127.1, 126.9, 126.7, 118.7, 114.7, 102.9, 97.1, 96.8, 84.7, 82.2, 82.1, 81.6, 79.7, 79.5, 77.8, 75.6, 75.1, 75.0, 74.9, 74.3, 74.2, 73.9, 73.6, 73.5, 73.4, 73.2, 73.2, 71.2, 71.1, 69.2, 69.1, 68.4, 55.8.

[0126] Example 5:

[0127] The preparation route of formula P14 of the present application is as follows:

[0128]

[0129] wherein OPTFAI is N-phenyltrifluoroacetimidate; OPVB is o-(l-phenylvinyl)benzoate.

[0130] The specific steps are as follows:

[0131] To a mixture solution of P13 (155 mg, 0.10 mmol) in DCM (1.0 mL) / MeCN (1.7 mL) / H2O (1.0 mL) was added cerium ammonium nitrate CAN (272 mg, 0.51 mmol) at 0 °C. The mixture was stirred at room temperature for 4 hours. Then the reaction was spun dry and diluted with ethyl acetate, and washed with saturated aqueous sodium bicarbonate solution, water and saturated brine successively. The organic phase was dried over anhydrous sodium sulfate and concentrated in vacuo. Purification by flash column chromatography (n-hexane: ethyl acetate, 4:1 to 2:1) gave a brown solid (98.0 mg, 68%). The above brown solid (98.0 mg, 0.07 mmol) and 2,2,2-trifluoro-N-phenylacetimidoyl chloride (22.0 mg, 0.10 mmol) were dissolved in acetone (1.0 mL) and anhydrous K2CO3 (29.0 mg, 0.21 mmol) was added. The reaction was stirred at room temperature overnight, then filtered and concentrated in vacuo. The residue was purified by flash column chromatography (n-hexane: ethyl acetate, 30:1 to 20:1, containing 1% Et3N) to give S5 (88.0 mg, 80%).

[0132] The glycosyl donor S5 (85.0 mg, 0.05 mmol) was dissolved in dry DCM / DMF (1.1 mL, v / v 15:1) under nitrogen protection, and mixed with freshly flame-dried The molecular sieves were stirred at room temperature for 10 min. The reaction solution was cooled to 0 °C, then TfOH (6.3 μL, 0.07 mmol) was added. After 30 min, acceptor II-11 (24.0 mg, 0.04 mmol) was added to the solution and the reaction was stirred at 0 °C slowly warming to room temperature until TLC analysis showed complete conversion of the acceptor. Then to the solution at 0 °C was added acceptor II-5 (14.0 mg, 0.04 mmol) and iodine (13.7 mg, 0.05 mmol). The resulting mixture was stirred at 0 °C to room temperature until TLC analysis indicated the reaction was complete. The solution was diluted with dichloromethane and quenched with saturated sodium thiosulfate. The organic phase was washed with water and saturated brine, dried over anhydrous sodium sulfate, filtered and concentrated in vacuo. The residue was purified by flash column chromatography (n-hexane: ethyl acetate, 20: 1) to give precursor compound P14 (36.0 mg, 45%) of drug PG545: 1H NMR (600 MHz, CDC13) δ 8.00 (d, J = 7.7 Hz, 2H), 7.54 (t, J = 7.4 Hz, 1H), 7.42 (t, J = 7.7 Hz, 2H), 7.30 - 7.19 (m, 39H), 7.12 (dd, J = 15.7, 7.3 Hz, 21H), 5.69 (d, J = 3.6 Hz, 1H), 5.56 (d, J = 3.5 Hz, 1H), 5.44 (d, J = 3.6 Hz, 1H), 5.33 (t, J = 8.4 Hz, 1H), 4.91 (dd, J = 11.7, 2.3 Hz, 2H), 4.85 - 4.73 (m, 6H), 4.68 - 4.63 (m, 2H), 4.54 - 4.39 (m, 14H), 4.26 (d, J = 12.2 Hz, 1H), 4.15 (t, J = 8.9 Hz, 1H), 4.11 - 3.99 (m, 5H), 3.95 - 3.86 (m, 4H), 3.84 - 3.74 (m, 4H), 3.70 - 3.64 (m, 2H), 3.57 - 3.48 (m, 7H), 3.38 (d, J = 10.5 Hz, 1H), 1.95 (dt, J = 12.8, 3.6 Hz, 1H), 1.90 - 1.84 (m, 1H), 1.83 - 1.75 (m, 1H), 1.65 - 1.42 (m, 8H), 1.33 - 1.19 (m, 7H), 1.14 - 0.95 (m, 11H), 0.89 (d, J = 6.4 Hz, 3H), 0.86 (d, J = 2.8 Hz, 3H), 0.85 (d, J = 2.8 Hz, 3H), 0.79 (dd, J = 12.3, 5.8 Hz, 1H), 0.68 (s, 3H), 0.62 (s, 3H), 0.55 (td, J = 11.5, 3.9 Hz, 1H);13C NMR (151 MHz, CDC13) δ 165.3, 139.1, 139.0,138.9,138.7,138.5,138.5,138.3,138.3,138.2,138.1,138.1,137.9,133.0,130.4,129.9,128.4,128.4,128.4,128.3,128.3,128.3,128.3,128.2,128.2,1 28.1,128.0,127.9,127.8,127.7,127.7,127.7,127.6,127.6,127.6,127.5,127.5,127.4,127.2,127.1,126.8,126.7,99.9,97.0,96.9,96.7,83.0,82.3,81.8 ,81.5,79.8,79.7,79.4,79.3,77.8,75.6,75.2,75.1,74.2,74.2,74.1,73.7,73.6,73.5,73.4,73.4,73.2,73.0,72.8,72.6,71.2,71.1,71.0,69.3,69.1,68.9 ,68.4,56.6,56.5,54.5,44.8,42.7,40.2,39.7,37.2,36.3,35.9,35.7,35.6,34.8,32.2,29.5,28.8,28.4,28.2,24.3,24.0,23.0,22.7,21.4,18.8,12.3,12.2。 .

[0133] Test case

[0134] To verify the effectiveness of using elemental iodine as a promoter in this invention, this invention is carried out according to... Figure 1 The synthetic route and 13 reaction experiments were conducted using different promoters and solvents (in Experiment 13, the solvent was a mixture of DCM and DMF in a molar ratio of 15:1). The results of synthesizing product P1 in I and II-1 show that the method of the present invention can be operated under relatively mild conditions (room temperature reaction) and provides a broad substrate range and high yield.

[0135] The use of weak nucleophiles is an economical and environmentally friendly strategy for modulating the stereoselectivity of glycosylation, requiring no additional synthetic steps and being easily removed after the reaction. This invention enables the highly stereoselective construction of 1,2-cis-glycosidic bonds using mixed solvents, and has a wide range of applications.

[0136] Obviously, the above embodiments are merely example for clearly illustrating but not limitation to the embodiments. Based on the above description, other different forms of changes or variations can be made by those skilled in the art. Here, all the embodiments need not and can not be enumerated. The obvious changes or variations derived from the above description are still within the protection scope of the present application.

Claims

1. A glycosylation reaction method using elemental iodine as a promoter, characterized by, The method comprises the following steps: carrying out a glycosylation reaction on raw materials containing a glycosylation donor, a glycosylation acceptor and a promoter to obtain a glycosylation reaction product; The promoter is elemental iodine. The glycosylation donor is selected from one of I-1, I-2 and I-3. ； The glycosylation acceptor is selected from one of the following compounds: The raw materials further contain a solvent, and the solvent is acetonitrile. The raw materials further contain a drying agent, and the drying agent is selected from at least one of 3A molecular sieve, 4A molecular sieve and 5A molecular sieve. The glycosylation reaction product is a compound as shown in the following formula: 。 2. The monatomic iodine as a promoter for the glycosylation reaction method according to claim 1, characterized by, The molar ratio of the glycosylation donor to the glycosylation acceptor is 1-2.0:

1. The molar ratio of the glycosylation acceptor to elemental iodine is 1:1.2-2.

5.

3. The monatomic iodine as a promoter for the glycosylation reaction method according to claim 1, characterized by, The concentration of the glycosylation acceptor in the raw materials is 0.033-0.1 mol / L.

4. The monatomic iodine as a promoter for the glycosylation reaction method according to claim 1, characterized by, The added amount of the drying agent is 2-5 grams per millimole of the glycosylation acceptor.

5. The monatomic iodine as a promoter for the glycosylation reaction method according to claim 1, characterized by, The reaction temperature is 0-25°C, and the reaction time is 1.5-24 hours; the reaction is carried out in an inert atmosphere, and the inert atmosphere is argon or nitrogen.

6. The monatomic iodine as a promoter for the glycosylation reaction method according to claim 1, characterized by, The method further comprises the following steps: After the glycosylation reaction is completed, quenching is carried out to obtain the glycosylation reaction product, and then the glycosylation reaction product is purified.

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