A method of glycosylation involving a trivalent iodine reagent

Abstract

A method for glycosylation with a triiodine reagent, characterized in that a glycosyl donor (I) is activated in the presence of a triiodine reagent and a transition metal catalyst, and then reacts with an acceptor (II) in the presence of an acid catalyst or directly to obtain a glycosylation product (III); in the glycosyl donor (I), Gly is a glycosyl group in which one or more hydroxyl groups on a sugar ring are protected by a protecting group; X is an oxygen, sulfur or selenium atom; R is an alkyl group or an aryl group; the acceptor (II) is selected from a nucleophile reagent including one or more free hydroxyl groups, such as a sugar, an alcohol, a phenol, a flavone, a carboxylic acid, a phosphoric acid, a pyrimidine, a purine, an amide, a sulfonamide, a guanidine, an arylamine, an indole, an enol silyl ether, a thiol or a sulfenol.

Description

Technical Field

[0001] This invention belongs to the field of glycochemistry technology, and more specifically, relates to a glycosylation method involving trivalent iodine reagent, and more particularly to a glycosylation method involving trivalent iodine reagent, in which a transition metal catalyst and an acid work together to activate the glycosyl donor. Background Technology

[0002] Carbohydrates are one of the four essential classes of biomolecules involved in the essence of life activities. They are widely distributed in animals, plants, microorganisms, and viruses, playing a vital role in organisms. Studies have shown that carbohydrates have promising applications in many fields, including anticancer, anti-inflammatory, antiviral, antidiabetic, immune regulation, and organ transplantation. Therefore, establishing efficient methods for the synthesis of carbohydrates is of great significance for studying the biological functions of natural carbohydrates and developing new carbohydrate drugs and vaccines. The key to carbohydrate synthesis is the efficient construction of glycosidic bonds through glycosylation reactions. However, since the first glycosylation reaction was developed in 1879, although carbohydrate chemists have developed dozens of different glycosylation reaction modes, mild, efficient, and substrate-compatible glycosylation methods are still very lacking. Many carbohydrates with good biological activity lack effective glycosylation methods for chemical synthesis, which greatly hinders carbohydrate research and the development of new carbohydrate drugs.

[0003] Over the past century, researchers have developed hundreds of different types of glycosyl donors, including halogenated sugars, glycosyl hemiacetals, acetates, enols, thioglycosides, selenoglycosides, trichloroacetylimine esters, and o-alkynylbenzoate esters. Among these, thioglycosides, selenoglycosides, and oxoglycosides are the most commonly used glycosyl donors in saccharide synthesis due to their ease of preparation and storage stability, playing a crucial role in oligosaccharide synthesis. Activation and glycosylation of thioglycoside and selenoglycoside donors have been reported. The activating reagents (or methods) for these glycosylation methods mainly fall into four categories: metal salts, halonium ion reagents, thiolonium ion reagents, and single-electron transfer reagents / methods. Early activators, especially heavy metal salts, often required stoichiometry, demanding reaction conditions, and suffered from high toxicity, difficult post-processing, and poor reproducibility. While some existing glycosylation methods promoted by halonium and thionium ion reagents have gained widespread use, they generally require excessive amounts of promoters for effective activation, and most promoters are expensive, toxic, and require less than mild reaction conditions with poor compatibility with reactants. Although some single-electron transfer reagents / methods have been reported, research in this field is still immature and in-depth, limiting their applicability. The applicant's team has also reported a method utilizing a metal Rh catalyst and Brønsted acid for sequential catalysis (H... + The method for activating glucosinolates (J. Am. Chem. Soc. 2019, 141, 11775-11780) compares with the method of this invention in terms of Rh / H +Catalytic activation methods for thioglycosides have several drawbacks, including the need to use only precious metal rhodium salts, the requirement for high catalytic equivalents of Rh catalysts for the activation of some thioglycosides, the need to use azo reagents which pose an explosion risk, and the limited applicability of glycosyl acceptors.

[0004] The demand for the synthesis of carbohydrate compounds, especially complex carbohydrate compounds, is increasing day by day. However, based on existing methods and technologies, it is still difficult to chemically synthesize a large number of carbohydrate substances with good application value and development potential. Therefore, developing a mild and efficient glycosylation method using glucosinolates and selenoglycolates as glycosyl donors is of great significance in the chemical synthesis of carbohydrates. Summary of the Invention

[0005] In view of the above-mentioned defects or improvement needs of existing methods, the present invention aims to provide a new glycosylation method. This method activates the glycosyl donor through a trivalent iodine reagent, which can avoid the use of dangerous azo reagents and expensive metal catalysts. It is a mild, efficient, easy-to-operate, low-cost, and widely applicable glycosylation method.

[0006] To achieve the above objectives, this invention provides a glycosylation method involving a trivalent iodine reagent. A glycosyl donor (I) is activated in the presence of a trivalent iodine reagent and a transition metal catalyst, and then reacts with an acceptor (II) under acid catalysis or directly to obtain the glycosylated product (III).

[0007] The reaction equation is as follows:

[0008]

[0009] In the glycosyl donor (I), Gly is a glycosyl group on the sugar ring in which one or more hydroxyl groups are protected by a protecting group; X is an oxygen (O), sulfur (S) or selenium (Se) atom; and R is an alkyl or aryl group.

[0010] In the glycosyl donor (I), when R is an alkyl group, it is preferably selected from ethyl (Et) or isopropyl (Et). i Pr), benzyl (Bn), and when R is aryl, preferably phenyl (Ph), p-methylphenyl (Tol) or 2-ethylphenyl (°EP);

[0011] The glycosyl Gly is selected from one of the structures shown in formula (Ia) or formula (Ib), wherein the substituent on the sugar ring may be hydrogen, alkyl, alkoxy, acyloxy, siloxy, substituted amino, cyclic acetal, cyclic ketal or glycosyl.

[0012] Preferably, formula (Ia) is selected from compounds with any of the following structures:

[0013]

[0014] Preferably, the formula (Ib) is selected from compounds with any of the following structures:

[0015]

[0016] The glycosyl acceptor (II) is a nucleophile Nu-H, selected from sugars, alcohols, phenols, flavonoids, carboxylic acids (no additional acid is needed), phosphates, pyrimidines, purines, amides, sulfonamides, guanidines, arylamines, indoles, enol silyl ethers, thiols, or thiophenols containing one or more free hydroxyl groups.

[0017] Preferably, the carbohydrate acceptor containing one or more free hydroxyl groups is selected from compounds with any of the following structures:

[0018]

[0019] Preferably, the alcohol or phenol receptor is selected from compounds with any of the following structures:

[0020]

[0021] Preferably, the flavonoid receptor is selected from compounds with the following structures:

[0022]

[0023] Preferably, the carboxylic acid or phosphate acceptor is selected from compounds with the following structures:

[0024]

[0025] Preferably, the pyrimidine receptor is selected from compounds with any of the following structures:

[0026]

[0027] Preferably, the purine receptor is selected from compounds with any of the following structures:

[0028]

[0029] Preferably, the amide receptor is selected from compounds with any of the following structures:

[0030]

[0031] Preferably, the sulfonamide receptor is selected from compounds with the following structures:

[0032]

[0033] Preferably, the guanidine receptor is selected from compounds with the following structures:

[0034]

[0035] Preferably, the arylamine receptor is selected from compounds with the following structures:

[0036]

[0037] Preferably, the indole receptor is selected from compounds with the following structures:

[0038]

[0039] Preferably, the enol silyl ether receptor is selected from compounds with any of the following structures:

[0040]

[0041] Preferably, the thiol or thiophenol acceptor is selected from compounds with any of the following structures:

[0042]

[0043] The trivalent iodine reagent is selected from the iodine ylide reagent of formula (IV-a) and the iminoiodide of formula (IV-b). Wherein, R 1 R 2 These can be the same or separate alkyl acyl (alkyl-CO), arylformyl (ArCO), alkylsulfonyl (alkyl-SO2), arylsulfonyl (ArSO2), alkoxyacyl (alkyl-OCO), phenoloxyacyl (ArO-CO), etc.; R 3 Ar is a sulfonyl group, preferably p-toluenesulfonyl (Ts); Ar is an aryl group, preferably phenyl (Ph), 2-methoxyphenyl (o-OMe-Ph), or 2-nitrophenyl (o-NO2-Ph).

[0044]

[0045] Preferably, the iodine ylide represented by formula (IV-a) is selected from compounds with any of the following structures:

[0046]

[0047] Preferably, the iminoiodide represented by formula (IV-b) is:

[0048]

[0049] More preferably, the trivalent iodine reagent is the iodine ylide reagent shown in formula (IV-1).

[0050] In one embodiment, the molar ratio of the glycosyl receptor shown in formula (II) to the trivalent iodine reagent can be 1:(1-6), preferably 1:(1-4), for example 1:(1.3-3), for example 1:(1.5-2).

[0051] The transition metal catalyst is a substance containing copper or rhodium. The copper-containing substance is selected from inorganic acid salts, organic acid salts, and copper complexes, such as cuprous chloride (CuCl), cuprous bromide (CuBr), cuprous iodide (CuI), cuprous bromide·dimethyl sulfide (CuBr·SMe2), cuprous tetrafluoroborate tetraacetonitrile (Cu(MeCN)4BF4), cuprous trifluoromethanesulfonate (CuOTf), cuprous acetate (CuOAc), cuprous hexafluoroacetylacetonate·1,5-cyclooctadiene (Cu(hfacac)(cod)), [1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]cuprous ((iPr)CuCl), and diphenyl... Cuprous phosphate (Ph2PO2Cu), cuprous thiophene-2-carboxylate (CuTc), copper chloride (CuCl2), copper bromide (CuBr2), copper acetate (Cu(OAc)2), copper acetylacetonate (Cu(acac)2), copper hexafluoroacetylacetonate (Cu(hfacac)2), copper p-toluenesulfonate (Cu(OTs)2), copper trifluoromethanesulfonate (Cu(OTf)2), copper sulfate (CuSO4), and copper trifluoromethanesulfonate toluene complex ((CuOTf)2·Toluene); substances containing rhodium are selected from rhodium(II) acetate dimer (Rh2(OAc)4) and rhodium(II) octanoate dimer (Rh2(oct)4). Preferably, the transition metal catalyst is selected from CuCl, CuBr, CuI, CuBr·SMe2, Cu(MeCN)4BF4, CuOTf, CuOAc, (iPr)CuCl, Ph2PO2Cu, CuTc, CuCl2, CuBr2, Cu(OAc)2, Cu(acac)2, Cu(OTf)2, (CuOTf)2·Toluene, Rh2(OAc)4, and Rh2(oct)4; more preferably selected from CuCl, CuBr, CuI, CuTc, Cu(MeCN)4BF4, and CuBr2; and most preferably selected from CuCl and CuBr.

[0052] In one embodiment, the amount of the transition metal catalyst, expressed as a mole percentage (mol%), is 0.01 to 10% of the glycosyl acceptor, for example, 0.01%, 0.025%, 0.05%, 0.1%, 0.25%, 0.5%, 5%, 10%, etc., and any value within a range or range of these arbitrary values, for example, 0.01 to 5%, 0.1 to 1%, 0.25 to 0.5%.

[0053] The acid catalyst is selected from Brønsted acids or Lewis acids. For example, the Brønsted acid is selected from methanesulfonic acid (MsOH), p-toluenesulfonic acid (TsOH), camphorsulfonic acid (CSA), trifluoromethanesulfonic acid (TfOH), 2,5-di-tert-butylpyridinium trifluoromethanesulfonic acid (TfOH·DTBP), 2,5-di-tert-butyl-4-methylpyridinium trifluoromethanesulfonic acid (TfOH·DTBMP), pyridinium trifluoromethanesulfonic acid (TfOH·Pyr), diisopropylamine trifluoromethanesulfonic acid (TfOH·iPr2NH), ethyl tetrafluoroborate, etc. The ether (HBF4·Et2O) and bis(trifluoromethanesulfonyl)imide (Tf2NH) are used. The Lewis acid is selected from boron trifluoride ether (BF3·Et2O), tris(pentafluorophenyl)borane (BCF), trimethylsilyl trifluoromethanesulfonate (TMSOTf), triethylsilyl trifluoromethanesulfonate (TESOTf), copper trifluoromethanesulfonate (Cu(OTf)2), cuprous trifluoromethanesulfonate (CuOTf), and triphenylmethyltetra(pentafluorophenyl)borate (Ph3CB(C6F5)4). Preferably, the acid is selected from TfOH, TfOH·DTBP, Tf2NH, TMSOTf, Cu(OTf)2, BF3·Et2O, or the glycosylation reaction is promoted by the acidity of the acidic substrate (carboxylic acid) itself without the addition of additional acid; more preferably, the acid is selected from TfOH, TMSOTf, and TfOH·DTBP.

[0054] Preferably, the amount of acid used is 5-30%, for example 5-25%, for example 10%-25%, or for example 10-20%, based on a mole percentage (mol%). When the glycosyl receptor (II) is a carboxylic acid, the amount of acid used may be 0.

[0055] Preferably, the reaction is carried out in an organic solvent. The organic solvent may be selected from one or more combinations of dichloromethane, trichloromethane, 1,2-dichloroethane, benzene, toluene, acetonitrile, and tetrahydrofuran. More preferably, the organic solvent is selected from dichloromethane, trichloromethane, 1,2-dichloroethane, or combinations thereof. Specifically, the reaction solvent can be selected by those skilled in the art based on common sense.

[0056] The reaction temperature can be from -78°C to 30°C, for example -60°C, -40°C, -20°C, -10°C, 0°C, 10°C, 25°C, or any range of these temperature values, preferably -78°C to 25°C, for example -78°C to 0°C, for example -60°C to 0°C, for example -40°C to 0°C, for example -10°C to 0°C. Specifically, the reaction temperature can be selected by those skilled in the art based on common sense.

[0057] In summary, compared with the prior art, the above-described technical solutions conceived by this invention mainly possess the following technical advantages:

[0058] (1) The reaction of this invention is mild and efficient, avoiding the use of dangerous azo reagents and expensive metal catalysts.

[0059] (2) The present invention has a wide range of applicable temperatures, a wide range of trivalent iodine reagents, transition metal catalysts and acid selection, which provides more flexible choices for the smooth glycosylation of different active substrates. It has a wide range of applicable substrates and is well applicable to different types and structures of glycosyl donors and acceptors.

[0060] (3) The trivalent iodine reagent used in this invention can be prepared rapidly in large quantities at low cost.

[0061] (4) The transition metal catalyst used in this invention can be selected from common, inexpensive and abundant metal salts or complexes, with low toxicity and smaller catalyst dosage.

[0062] (5) The acid catalyst used in this invention can be selected from commercially available Brønsted acid or Lewis acid; (6) The donor used in this invention can be a thioglycoside, selenoglycoside or oxyglycoside donor with mature synthesis technology, stable properties, and easy preparation and storage.

[0063] In summary, the efficient glycosylation method involving trivalent iodine reagents provided by this invention effectively overcomes the problems of harsh reaction conditions, narrow substrate applicability, or complex donor structures that are difficult to prepare, as well as poor donor stability and difficulty in storage that exist in existing methods, providing a new and easy-to-implement scheme for the synthesis of carbohydrates. Detailed Implementation

[0064] To make the objectives, technical solutions, and advantages of this invention clearer, the invention will be further described in detail below with reference to embodiments. It should be understood that the specific embodiments described herein are merely illustrative and not intended to limit the invention. Furthermore, the technical features involved in the various embodiments of this invention described below can be combined with each other as long as they do not conflict with each other.

[0065] Unless otherwise stated, all raw materials and reagents used in this invention are commercially available. All reagents are commercial grade and used according to received standards. All moisture-sensitive reactions were carried out under an argon atmosphere. Reactions were monitored by thin-layer chromatography (TLC) with detection by ultraviolet absorption (254 nm), and if necessary, by spraying with a 10% (v / v) sulfuric acid ethanol solution and carbonization at 80-150°C. Flash column chromatography was performed using silica gel H2. 1 H and 13 120-200 NMR spectroscopy was performed using deuterated chloroform (CDCl3) as the deuterating reagent on Bruker AV 400 and Bruker Av 600 spectra. Chemical shifts (δ) are expressed in ppm, with tetramethylsilane as an internal standard. Coupling constants (J) are expressed in Hz.

[0066] Unless otherwise stated, the scientific and technical terms and abbreviations used in this invention have the meanings commonly understood by those skilled in the art. For example, in this invention, "equivalent" refers to the ratio of the amounts of the substances participating in the reaction; and some abbreviations have the following meanings:

[0067] abbreviations Chinese meaning abbreviations Chinese meaning Me methyl Nap Naphthyl Et Ethyl Ns p-Nitrobenzenesulfonyl <![CDATA[ i Pr]]> Isopropyl Ph Phenyl Ac Acetyl Phth Phthaloyl Bn benzyl TBS tert-butyldimethylsilyl Bz benzoyl TBDPS tert-butyldiphenylsilyl <![CDATA[ t This]]> tert-butyl TMS Trimethylsilyl Boc tert-Butoxycarbonyl TIPS Triisopropylsilyl n-Bu n-Butyl Tol Toluene Cbz benzyloxycarbonyl Ts p-Toluenesulfonyl Fmoc fluorene methyloxycarbonyl Tf Trifluoromethanesulfonyl MeCN Acetonitrile DCE 1,2-Dichloroethane MsOH mesylate BSTFA Bis(trimethylsilyl)trifluoroacetamide

[0068] The glycosylation method of the present invention includes the steps of: mixing a glycosyl donor (I) with a trivalent iodine reagent, adding a transition metal catalyst to undergo a pre-activation reaction, then adding an acceptor (II) and an acid catalyst to undergo a glycosylation reaction, thereby obtaining a glycosylated product (III); or mixing a glycosyl donor, an acceptor, and a trivalent iodine reagent, adding a transition metal catalyst to undergo an activation reaction, then adding an acid catalyst to undergo a glycosylation reaction, thereby obtaining a glycosylated product (III). Detailed experimental procedures can be found in the following examples.

[0069] Examples 1-54

[0070] In Examples 1-22 and 24-51: Glycosyl donor compound I (1.2 eq.) was mixed with trivalent iodine reagent in dichloromethane as a reaction solvent. A transition metal catalyst was added at the temperatures shown in Table 1, and the reaction proceeded until compound I disappeared or ceased to decrease. Then, acceptor compound II (1.0 eq.) was added sequentially and reacted with an acid catalyst. After the reaction was monitored by TLC until complete, a saturated NaHCO3 solution was added to stop the reaction, and the reaction mixture was extracted with dichloromethane. The extract was concentrated and purified by silica gel column chromatography to obtain the glycosylated product.

[0071]

[0072] In Examples 23 and 52-54: The glycosyl donor (I) and acceptor (II), along with trivalent iodine reagent, were mixed in dichloromethane as the reaction solvent. A transition metal catalyst was added at the temperatures shown in Table 1 until the reaction was complete. Then, an acid catalyst was added, and the reaction was stopped by adding saturated NaHCO3 solution after TLC monitoring. The reaction solution was then extracted with dichloromethane. The extract was concentrated and purified by silica gel column chromatography to obtain the glycosylated product.

[0073]

[0074] Table 1

[0075]

[0076]

[0077]

[0078]

[0079] III-01: 1 H NMR(600MHz,CDCl3)δ7.42(m,2H),7.35-7.25(m,13H),5.48(dd,J=

[0080] 1.8,3.0Hz,1H),5.30(dd,J=3.6,9.6Hz,1H),5.14(d,J=1.8Hz,1H,H-1′),5.02(t,J=9.6Hz,1H),4.85(d,J=12.0Hz,1H),4.81(d,J=11.4Hz,1H),4.68(d,J=11.4Hz,1H),4.63(d,J=11.6Hz,1H),4.60(d,J=3.6Hz,1H,H-1),4.54(s,2H),4.10(d,J=1.8Hz,1H),3.96(dd,J=3.6,10.2Hz,1H),3.93(m,2H),3.88(dd,J=2.4,9.6Hz,1H),3.62(dd,J=6.6,9.6Hz,1H),3.58(dd,J=6.6,9.6Hz,1H),3.36(s,3H),2.04(s,3H),2.02(s,3H),1.98(s,3H),1.12(d,J=6.0Hz,3H).

[0081] III-02: 1 H NMR(400MHz,CDCl3)δ7.33-7.18(30H,m,Ar-CH),5.00(1H,s,H-1),4.90(1H,d,J=10.4Hz,PhCH2),4.86(1H,d,J=11.2Hz,PhCH2),4.69(2H,d,J=11.6Hz,PhCH2),4.56-4.51(7H,m,6xPhCH2,H-1’,4.44(1H,d,J=12.0Hz,PhCH2),4.37(1H,d,J=12.0Hz,PhCH2),3.91-3.84(1H,m,H-5),3.77-3.70(3H,m),3.66-3.39(6H,m),3.30(3H,s,OCH3),1.01(3H,d,J=6.0Hz,H-6).

[0082] As can be seen from the above embodiments, different donor structures, such as ethylthioglycoside, isopropylthioglycoside, benzylthioglycoside, p-tolylthioglycoside, phenylthioglycoside, and o-ethylphenylthioglycoside, all exhibit good effects. Ethylthioglycoside, isopropylthioglycoside, benzylthioglycoside, and other alkylthioglycosides are preferred, and ethylthioglycoside is more preferred. Good yields can be obtained by using different trivalent iodine reagents, preferably IV-1 to IV-8, and more preferably IV-1.

[0083] Good yields can be obtained by using different transition metal catalysts, such as different copper and rhodium salts. Preferred transition metal catalysts include cuprous chloride (CuCl), cuprous bromide (CuBr), cuprous iodide (CuI), cuprous bromide·dimethyl sulfide (CuBr·SMe2), cuprous tetrafluoroborate tetraacetonitrile (Cu(MeCN)4BF4), cuprous trifluoromethanesulfonate (CuOTf), cuprous acetate (CuOAc), and [1,3-bis(2,6-]chloro[] The following are listed: [diisopropylphenyl]imidazolium-2-yl]cuprous ((iPr)CuCl), [diphenyl]copper(phosphate) (Ph2PO2Cu), [thiophene-2-carboxylate]copper(CuTc), [copper(chloride)](CuCl2), [copper(bromine)](CuBr2), [copper(acetate)](Cu(OAc)2), [copper(acetylacetonate)](Cu(acac)2), [copper(hexafluoroacetylacetonate)](Cu(hfacac)2), [copper(p-toluenesulfonate)](Cu(OTs)2), [copper(trifluoromethanesulfonate)](Cu(OTf)2), [copper(trifluoromethanesulfonate)](CuOTf)2·Toluene), [Rh2(OAc)4](Rh2(oct)4](Rh2(oct)4), etc.; wherein, by molar percentage, the amount of the transition metal catalyst is 0.01–10% of the glycosyl acceptor, for example 0.01–5%, for example 0.1–1%, 0.25–0.5%, for example 0.5%.

[0084] Different acid catalysts, such as Brønsted acids, Brønsted salts, or Lewis acids, can be used to exert catalytic effects. For example, preferred acid catalysts are trifluoromethanesulfonic acid (TfOH), 2,5-di-tert-butylpyridinium trifluoromethanesulfonic acid (TfOH·DTBP), 2,5-di-tert-butyl-4-methylpyridinium trifluoromethanesulfonic acid (TfOH·DTBMP), bis(trifluoromethanesulfonyl)imide (Tf2NH), trimethylsilyl trifluoromethanesulfonate (TMSOTf), copper trifluoromethanesulfonate (Cu(OTf)2), etc. The amount of the acid catalyst used, by molar percentage, is 5% to 30% of the glycosyl acceptor, more preferably 10% to 25%, for example 10% to 20%.

[0085] Examples 55-103

[0086] Unless otherwise specified, the standard operating procedure for the glycosylation reaction in Examples 55-103 is as follows: a glycosyl donor, iodoylide IV-1, and a dried molecular sieve are prepared. MS (in the form of 160 mg / mL CH2Cl2 solution) was placed in a Schlenk flask, sealed with a rubber stopper, and deoxygenated by argon purging over a double-row tube. Then, anhydrous CH2Cl2 (c = 0.1 M, calculated based on a reactant equivalent of 1.0) was added under an argon atmosphere. The reaction system was pre-cooled to 0°C, and a 0.02 M CuCl-acetonitrile solution (0.5 mol%) was added. The reaction was carried out at 0°C for approximately 5 minutes until complete. Then, a glycosyl acceptor and an acid catalyst (20 mol%) were added, and the reaction was carried out at 0°C until complete. The reaction was terminated by adding saturated NaHCO3 solution. The concentrated extract was purified by silica gel column chromatography to obtain the glycosylated product. In some implementation examples, where the content of the special instructions differs from the standard operating procedure, the content of the special instructions shall prevail.

[0087] Example 55: Trivalent iodine reagent participates in glycosylation to prepare compound III-03

[0088]

[0089] According to the standard operating procedure, donor I-15 (30.0 mg, 0.058 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (24.1 mg, 0.072 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-15 was completely converted, acceptor II-01 (22.3 mg, 0.048 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, a white solid compound III-03 (42.5 mg, 96%) was obtained. 1H NMR (600MHz, CDCl3) δ7.93 (d, J=7.8Hz, 2H, Ar-H), 7.86 (d, J=7.8Hz, 2H, Ar-H), 7.54-7.25 (m, 26H, Ar-H), 5.56 (t, J=9.6Hz, 1H), 5.44 (s, 1H), 5.39 ( t,J=8.4Hz,1H),4.98(d,J=10.8Hz,1H,PhCH2),4.86(d,J=11.4Hz,1H,PhCH2),4.78(d,J=12.6Hz,1H,PhCH2),4.73(d,J=7.8Hz,1H),4.70(d,J=12. 0Hz,1H,PhCH2),4.63(d,J=12.0Hz,1H,PhCH2),4.55(d,J=3.6Hz,1H),4.31(d,J=12.0Hz,1H,PhCH2),4.22(dd,J=5.4,10.8Hz,1H),3.95(t,J=9.0H z,1H),3.85(t,J=9.0Hz,1H),3.78(t,J=9.6Hz,1H),3.64(dd,J=3.0,10. 8Hz,1H),3.54–3.49(m,2H),3.46(m,1H),3.39-3.35(m,2H),3.28(s,3H), 13 C NMR (150MHz, CDCl3) δ165.63,165.07,139.54,138.44,137.82,136.99,133.42,133. 16,129.87,129.57,129.23,129.16,128.96,128.66,128.55,128.49,128.41,128.33 ,128.30,128.17,127.92,127.61,127.44,126.27,101.50,100.90,98.50,80.03,78 .98,75.49,73.76,73.65,73.03,72.34,69.64,68.72,67.53,66.44,55.48.HRMS(ESI + ):calc.for C 55 H 54 NaO 13 [M+Na] + 945.3457, found: 945.3445.

[0090] Example 56: Trivalent iodine reagent participates in glycosylation to prepare compound III-04

[0091] Option 1

[0092]

[0093] According to the standard operating procedure, donor I-32 (35.2 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-32 was completely converted, acceptor II-01 (20.0 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-04 (43.8 mg, 94%) was obtained.

[0094] Option 2

[0095]

[0096] According to the standard operating procedure, donor I-32 (35.2 mg, 0.052 mmol, 1.2 equivalents), acceptor II-01 (20.0 mg, 0.043 mmol, 1.0 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and TfOH was added after I-32 was completely converted. After the reaction was complete, the colorless syrupy compound III-04 (41.0 mg, 88%) was obtained. 1H NMR(400MHz, CDCl3)δ7.49–7.26(m,15H,Ar-H),5.42–5.36(m,1H),5.33(d,J=3.9H z,1H),5.07(t,J=8.5Hz,1H),5.02(t,J=7.6Hz,1H),4.96(d,J=11.6Hz,1H),4.87( dd,J=10.6,3.6Hz,1H),4.79(d,J=12.0Hz,1H),4.72(dd,J=15.3,5.7Hz,3H),4.57 (dd,J=8.0,4.3Hz,2H),4.46(d,J=8.1Hz,1H),4.42(d,J=12.0Hz,1H),4.22(dd,J=1 2.5,3.5Hz,1H),4.14(dd,J=12.0,2.8Hz,1H),4.07(dd,J=12.1,3.9Hz,1H),3.99( dd,J=12.5,2.1Hz,1H),3.91–3.83(m,3H),3.83–3.77(m,2H),3.61(t,J=9.4Hz,2H) ,3.47(dd,J=9.2,3.7Hz,1H),3.37(s,3H),3.15(dt,J=9.7,3.3Hz,1H),2.11(s,3H ),2.08(s,3H),2.05(d,J=2.5Hz,3H),2.02(s,3H),1.98(s,3H),1.97–1.92(m,6H).

[0097] Example 57: Trivalent iodine reagent participates in glycosylation to prepare compound III-05

[0098] Option 1

[0099]

[0100] According to the standard operating procedure, donor I-34 (22.8 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-34 was completely converted, acceptor II-01 (20.0 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-05 (30.4 mg, 89%) was obtained.

[0101] Option 2

[0102]

[0103] According to the standard operating procedure, donor I-34 (22.8 mg, 0.052 mmol, 1.2 equivalents), acceptor II-01 (20.0 mg, 0.043 mmol, 1.0 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents), and molecular sieve were added to the reaction flask. CuCl was added, and after I-34 was completely converted, TfOH was added. After the reaction was complete, the colorless syrupy compound III-05 (30.1 mg, 88%) was obtained. 1 H NMR (400MHz, CDCl3) δ7.40-7.20(15H,m,Ar-H),5.00(1H,t,J=9.2Hz),4.97-4.91(2H,m),4.87(1H,t,J=9.2Hz),4.75-4.70(3H, m,PhCH2),4.57(1H,d,J=11.6Hz,PhCH2),4.55(1H,d,J=3.2Hz,H-1),4.47(1H,d,J=8.0Hz,H-1′),4.40(1H,d,J=12.0Hz,PhCH2) 4.12(1H,dd,J=12.0,4.0Hz,H-6a),3.88-3.79(3H,m),3.74(1H,dd,J=10.8,2.8Hz),3.60-3.56(2H,m),3.45(1H,dd,J=8.4,4.4 Hz)3.34(3H,s,-OCH3),3.30-3.26(1H,m),1.98(3H,s,-COCH3),1.96(3H,s,-COCH3),1.93(3H,s,-COCH3),1.92(3H,s,-COCH3).

[0104] Example 58: Trivalent iodine reagent participates in glycosylation to prepare compound III-06

[0105]

[0106] According to the standard operating procedure, donor I-11 (16.7 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.0 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-11 was completely converted, acceptor II-02 (20.0 mg, 0.042 mmol, 1.0 equivalents) and TfOH were added. After the reaction was complete, the colorless syrupy compound III-06 (29.8 mg, 95%) was obtained. 1H NMR(600MHz, CDCl3)δ8.00(2H,dd,J=1.2,7.8Hz,Ar-H),7.58(1H,m,Ar-H),7.45(2H,t,J=7.8 Hz,Ar-H),7.41(2H,d,J=7.2Hz,Ar-H),7.35-7.27(8H,m,Ar-CH),5.18(1H,dd,J=8.4,10.2Hz, H-2′),5.11(1H,d,J=3.0Hz,H-4),5.00(1H,d,J=10.8Hz,PhCH2),4.98(1H,d,J=11.4Hz,PhCH 2),4.90(1H,dd,J=3.6,10.8Hz,H-3),4.76(1H,d,J=8.4Hz,H-1′),4.75(1H,d,J=12.0Hz,PhCH 2),4.63(1H,dd,J=1.8,11.4Hz,H-6a′),4.61(1H,d,J=12.0Hz,PhCH2),4.57(1H,d,J=3.6Hz, H-1),4.36(1H,dd,J=5.4,11.4Hz,H-6b),4.00(1H,t,J=9.0Hz,H-4),3.94(1H,m,H-5′),3.85( 1H,dd,J=8.4,9.6Hz,H-3),3.54(1H,dd,J=3.6,9.6Hz,H-2),3.48(1H,m,H-5),3.38(3H,s,OC H3),2.14(3H,s,COCH3),2.04(3H,s,COCH3),1.95(3H,s,COCH3),0.99(3H,d,J=6.6Hz,H-6′).

[0107] Example 59: Trivalent iodine reagent participates in glycosylation to prepare compound III-07

[0108] Option 1

[0109]

[0110] According to the standard operating procedure, donor I-18 (27.9 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-18 was completely converted, acceptor II-03 (20 mg, 0.043 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was complete, the colorless syrupy compound III-07 (43.4 mg, 93%) was obtained.

[0111] Option 2

[0112]

[0113] According to the standard operating procedure, donor I-18 (27.9 mg, 0.052 mmol, 1.2 equivalents), acceptor II-03 (20 mg, 0.043 mmol, 1.0 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-18 was completely converted, TfOH·DTBP was added. After the reaction was complete, the colorless syrupy compound III-07 (35.9 mg, 89%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.36-7.24(28H,m,Ar-H),7.18(m,2H,Ar-H),4.99(1H,t,J=8.4Hz),4.80(1H,d,J=12.0Hz),4.77(2H,d ,J=11.4Hz),4.74(1H,d,J=12.0Hz),4.67(2H,d,J=12.0Hz),4.64(1H,d,J=3.6Hz,H-1),4.58(1H,d,J=11.4Hz),4.55(1H,d,J =10.8Hz,H-1'),4.50(1H,d,J=12.0Hz),4.47(2H,d,J=12.0Hz),4.41(1H,d,J=12.0Hz),4.03(1H,d,J=2.4Hz),3.88(1H,m), 3.84(1H,dd,J=2.4,9.6Hz),3.80-3.78(2H,m),3.70-3.61(5H,m),3.39-3.37(1H,m),3.35(s,3H,OCH3),1.74(3H,s,COCH3).

[0114] Example 60: Trivalent iodine reagent participates in glycosylation to prepare compound III-08

[0115]

[0116] According to the standard operating procedure, donor I-28 (25.6 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-28 was completely converted, acceptor II-03 (20 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-08 (36.2 mg, 94%) was obtained. 1H NMR (400MHz, CDCl3) δ7.43–7.16 (m, 30H, Ar-H), 5.50 (s, 1H), 4.78 (d, J = 12.4Hz, 1H, Ph CH2),4.78(d,J=11.6Hz,1H,PhCH2),4.70(d,J=3.6Hz,1H,H-1),4.69–4.63(m,3H,H-1′,PhC H2),4.59–4.51(m,3H,PhCH2),4.49(d,J=12.0Hz,1H,PhCH2),4.47–4.41(m,2H,PhCH2),4.12 –4.02(m,3H),3.91–3.82(m,3H),3.79–3.73(m,2H),3.69(dd,J=10.0,5.6Hz,1H),3.61(dd, J=10.0,6.4Hz,1H),3.35(s,3H),3.32(dd,J=10.0,3.0Hz,1H),3.09(td,J=10.0,4.8Hz,1H). 13 CNMR(100MHz,CDCl3)δ139.0,138.6,138.6,138.5,138.4,137.7,129.0,128 .7,128.5,128.5,128.4,128.4,128.3,128.2,128.1,128.0,127.9,127.7,1 27.7,127.6,127.5,127.5,126.2,102.8,101.4,98.5,78.6,78.6,78.4,76. 5,75.4,75.0,73.8,73.4,73.4,72.3,69.8,69.3,68.7,67.7,55.5.HRMS(ESI + ):calc.for C 55 H 58 NaO 11 [M+Na] + 917.3871, found: 917.3884.

[0117] Example 61: Trivalent iodine reagent participates in glycosylation to prepare compound III-09

[0118]

[0119] According to the standard operating procedure, donor I-36 (16.7 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-36 was completely converted, acceptor II-03 (20 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was complete, the colorless syrupy compound III-09 (28.9 mg, 93%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.38 (d, J=7.2Hz, 2H, Ar-H), 7.32 (dd, J=4.8, 12.6Hz, 10H, Ar-H),7.28(m,1H,Ar-H),7.27(m,2H,Ar-H),5.38(d,2H,H-1',H-2'),5.29(dd,J =4.2,7.2Hz,1H,H-3'),4.81(d,J=11.4Hz,2H,PhCH2),4.66(d,J=11.4Hz,1H,Ph CH2),4.65(d,J=12.0Hz,1H,PhCH2),4.60(d,J=2.4Hz,1H,H-1),4.55(d,J=11.4H z,1H,PhCH2),4.51(d,J=11.4Hz,1H,PhCH2),4.29(dd,J=3.6,11.6Hz,1H,H-5a' ),4.21(m,1H,H-4'),4.13(s,1H,H-4),4.09(dd,J=6.6,12.0Hz,1H,H-5b'),3.90 (m,1H,H-5),3.87(d,J=1.8Hz,2H),3.68(dd,J=9.6,6.6Hz,1H,H-6a),3.55(dd,J =6.0,9.0Hz,1H,H-6b),3.36(s,3H,OMe),2.04(s,3H),2.00(s,3H),1.91(s,3H). 13 C NMR (100MHz, CDCl3) δ170.56,169.55,169.26,138.51,138.29,138.19,128.43,128.38,128.27,127.80,127.77,127.64,127.50,127.46, 107.15,98.72,78.09,78.01,76.16,75.77,74.91,73.71,73.43,73.40,71.13,69.20,68.65,64.63,55.37,20.74,20.54,20.42.HRMS (ESI +):calc.for C 39 H 46 NaO 13 [M+Na] + 745.2831, found: 745.2823.

[0120] Example 62: Trivalent iodine reagent participates in glycosylation to prepare compound III-10

[0121] Option 1

[0122]

[0123] According to the standard operating procedure, donor I-10 (20.3 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-10 was completely converted, acceptor II-04 (20.0 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was complete, the colorless syrupy compound III-10 (32.5 mg, 95%) was obtained.

[0124] Option 2

[0125]

[0126] According to the standard operating procedure, donor I-10 (20.3 mg, 0.052 mmol, 1.2 equivalents), acceptor II-04 (20.0 mg, 0.043 mmol, 1.0 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and TfOH was added after I-10 was completely converted. After the reaction was complete, the colorless syrupy compound III-10 (29.1 mg, 85%) was obtained. 1H NMR(400MHz, CDCl3)δ7.36-7.23(13H,d,J=7.6Hz,Ar-CH),7.15-7.13(2H,m,Ar-CH),5.43(1H,dd,J=2.0,3.2Hz,H -2),5.39(1H,dd,J=3.6,10.0Hz,H-3),5.23(1H,t,J=9.6Hz,H-4),4.95(1H,s,H-1),4.81(1H,d,J=10.8Hz,PhCH2 ),4.77(1H,d,J=2.0Hz,H-1′),4.69(1H,d,J=12.0Hz,PhCH2),4.63-4.54(3H,m,PhCH2),4.48(1H,d,J=10.8Hz,Ph CH2),4.22(1H,dd,J=5.2,11.6Hz,H-6a),4.20-4.15(1H,m,H-5),4.09(1H,dd,J=2.0,11.6Hz,H-6b),3.92(1H,br s,H-2′),3.90-3.82(2H,m,H-6a′,H-4′),3.75-3.70(3H,m,H-3′,H-5′,H-6b′),3.33(3H, s,OCH3),2.09(3H,s,COCH3),2.07(3H,s,COCH3),1.98(3H,s,COCH3),1.97(3H,s,COCH3).

[0127] Example 63: Trivalent iodine reagent participates in glycosylation to prepare compound III-11

[0128]

[0129] According to the standard operating procedure, donor I-18 (27.7 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-18 was completely converted, acceptor II-05 (20.0 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-11 (37.6 mg, 93%) was obtained. 1H NMR (400MHz, CDCl3) δ7.37–7.25(m,30H),5.03(t,J=8.8Hz,1H),4.95(d,J=11.2Hz,1H),4. 83–4.73(m,5H),4.63(d,J=11.6Hz,1H),4.62(d,J=12.0Hz,1H)4.58–4.48(m,5H),4.37(d,J =8.0Hz,1H,H-1),4.07(dd,J=10.8,1.6Hz,1H),3.95(t,J=9.2Hz,1H),3.76–3.69(m,2H),3 .68–3.59(m,4H),3.50(dd,J=9.6,3.6Hz,1H),3.48–3.40(m,2H),3.33(s,3H),1.85(s,3H).

[0130] Example 64: Trivalent iodine reagent participates in glycosylation to prepare compound III-12

[0131]

[0132] According to the standard operating procedure, donor I-14 (24.8 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (28.8 mg, 0.086 mmol, 2.0 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-14 was completely converted, acceptor II-05 (20 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-12 (35.3 mg, 93%) was obtained. 1H NMR(400MHz,CDCl3)δ7.53(4H,br s,Ar-H),7.30-7.19(13H,m,Ar-H),7.01-6.98(2H,m,Ar-H),5.77(1H,dd ,J=8.8,10.4Hz,H-2),5.39(1H,d,J=8.8Hz,H-1),5.13(1H,t,J=10.0,10 .2Hz,H-3),4.80(1H,d,J=10.8Hz,PhCH2),4.66(1H,d,J=12.0Hz,PhCH2),4.60(1H,d,J=10.8Hz,PhCH2),4.52(1H,d,J=12.0Hz,PhCH2),4.38-4.3 2(3H,m),4.30(1H,dd,J=4.4,12.0Hz),4.12(1H,dd,J=2.4,12.4Hz),4.08-4.03(2H,m),3.84-3.83(1H,m),3.82(1H,dd,J=9.6Hz),3.61(2H,dd,J =4.0,12.8Hz),3.33(1H,dd,J=3.6,9.6Hz),3.20(1H,t,J=9.2Hz),3.12(3H,s,OCH3),2.04(3H,s,COCH3),1.98(3H,s,COCH3),1.80(3H,s,COCH3).

[0133] Example 65: Trivalent iodine reagent participates in glycosylation to prepare compound III-13

[0134]

[0135] According to the standard operating procedure, donor I-35 (24.7 mg, 0.034 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (14.1 mg, 0.042 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-35 was completely converted, acceptor II-06 (9.0 mg, 0.028 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-13 (24.4 mg, 94%) was obtained. 1H NMR (600MHz, CDCl3) δ8.10–8.08(m,2H,Ar-H),8.05–8.03(m,2H,Ar-H),7.95–7.92(m,2H,Ar-H) ,7.84–7.81(m,2H,Ar-H),7.61–7.56(m,2H,Ar-H),7.52–7.47(m,1H,Ar-H),7.45–7.34(m,7H,Ar -H),7.29–7.25(m,2H,Ar-H),6.09(t,J=10.2Hz,1H,H-4'),5.90(dd,J=10.2,3.6Hz,1H,H-3'), 5.70(dd,J=3.0,1.8Hz,1H,H-2'),5.48(dd,J=10.2,9.6Hz,1H,H-3),5.42(d,J=1.8Hz,1H,H-1') ,5.15(t,J=9.6Hz,1H,H-4),5.10(d,J=6.8Hz,1H,CH2),4.95(d,J=3.6Hz,1H,H-1),4.88(dd,J= 10.2,3.6Hz,1H,H-2),4.83(d,J=6.6Hz,1H,CH2),4.71–4.67(m,1H,H-6'a),4.50–4.43(m,2H,H- 5',H-6'b),3.96–3.90(m,1H,H-5),3.85(dd,J=11.4,4.2Hz,1H,H-6a),3.71(dd,J=11.4,2.4Hz ,1H,H-6b),3.40(s,3H,-OCH3),2.06(s,3H,-COCH3),2.00(s,3H,-COCH3),1.97(s,3H,-COCH3).

[0136] Example 66: Trivalent iodine reagent participates in glycosylation to prepare compound III-14

[0137] Option 1

[0138]

[0139] According to the standard operating procedure, donor I-12 (17.4 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-12 was completely converted, acceptor II-07 (20 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-14 (29.6 mg, 93%) was obtained.

[0140] Option 2

[0141]

[0142] According to the standard operating procedure, donor I-12 (17.4 mg, 0.052 mmol, 1.2 equivalents), acceptor II-07 (20 mg, 0.043 mmol, 1.0 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and TfOH was added after I-12 was completely converted. After the reaction was complete, the colorless syrupy compound III-14 (29.6 mg, 93%) was obtained. 1 H NMR (400MHz, CDCl3) δ7.31-7.28(10H,m,Ar-H),5.14-5.04(4H,m),4.93-4.87(3H,m),4.68(1H,d,J=10.0Hz ),4.63(1H,d,J=3.2Hz,H-1),4.57(1H,d,J=10.0Hz),4.33(1H,dd,J=2.0,12.0Hz,H-6a′),4.27(1H,dd,J=4 .8,12.0Hz,H-6b′),3.96(1H,m,H-5′),3.88(1H,t,J=9.6,9.2Hz,),3.74(1H,m,H-5),3.61(2H,m),3.33(3H ,s,CH3),2.16(3H,s,CH3),2.05(3H,s,CH3),2.04(3H,d,CH3),1.96(3H,s,CH3),1.09(3H,d,J=6.4Hz,CH3). 13 C NMR (100MHz, CDCl3) δ170.96,170.89,170.34,169.59,156.02,137.65,136.38,128.85,128.76,128.49,128.33,100.16,99.0 3,81.39,75.80,74.15,69.79,69.18,68.67,67.29,63.26,55.33,54.89,29.89,21.23,21.18,20.90,20.83,15.99.HRMS(ESI + ):calc.for C 36 H 45 NNaO 15 [M+Na] + 754.2681, found: 754.2677.

[0143] Example 67: Trivalent iodine reagent participates in glycosylation to prepare compound III-15

[0144]

[0145] According to the standard operating procedure, donor I-11 (16.4 mg, 0.049 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (20.5 mg, 0.062 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-11 was completely converted, acceptor II-08 (20 mg, 0.041 mmol, 1.0 equivalents) and TfOH were added. After the reaction was complete, the colorless syrupy compound III-15 (29.6 mg, 95%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.47 (2H, d, J = 7.2Hz, Ar-H), 7.35-7.30 (8H, m, Ar-H), 5. 18(2H,m,H-4′,H-2′),5.02(1H,d,J=10.8Hz,PhCH2),4.95(1H,dd,J=3.6,10. 8Hz,H-3′),4.89(1H,d,J=11.4Hz,PhCH2),4.82(1H,d,J=7.8Hz,H-1′),4.79( 1H,d,J=12.0Hz,PhCH2),4.64(1H,d,J=12.6Hz,PhCH2),4.58(1H,d,J=3.6Hz, H-1),3.93(1H,t,J=9.0Hz,H-3),3.83(1H,dd,H-6a,HH-4),3.78(1H,dd,J=4. 2,11.4Hz,H-6b),3.59(1H,dq,H-5′),3.55(1H,m,H-5),3.47(1H,dd,J=3.6,9 .6Hz,H-2),3.38(3H,s,OMe),2.17(3H,s),2.08(3H,s),2.00(3H,s),1.08(3H ,d,J=6.0Hz,CH3),0.91(9H,s,C(CH3)3),0.09(3H,s,CH3),0.07(3H,s,CH3). 13C NMR (150MHz, CDCl3) δ170.69,170.26,169.37,139.36,138.34,128.35,128.07,127.99,127.75,127.59,127.24,100.23,97.93,80.03,79.6 9,76.65,75.19,73.45,71.72,70.94,70.37,70.03,69.07,61.55,55.08,25.86,20.91,20.71,20.65,18.24,16.01,-5.06,-5.25.HRMS(ESI + ):calc.for C 39 H 56 NaO 13 Si[M+Na] + 783.3382, found: 783.3366.

[0146] Example 68: Trivalent iodine reagent participates in glycosylation to prepare compound III-16

[0147]

[0148] According to the standard operating procedure, donor I-16 (33.1 mg, 0.052 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (26.1 mg, 0.078 mmol, 1.5 equivalent) and molecular sieve were added to the reaction flask. CuBr was added and after I-16 was completely converted, acceptor II-09 (27.0 mg, 0.062 mmol, 1.2 equivalent) and TfOH were added. After the reaction was completed, the white solid compound III-16 (48.2 mg, 92%) was obtained. 1H NMR(400MHz,CDCl3)δ7.92–7.90(m,4H,Ar-H),7.88–7.84(m,4H,Ar-H),7.50–7.43(m,3H,Ar-H),7.41–7.36(m,1H,Ar-H),7.36–7.23(m,13H,Ar-H),5.55(t,J=9.6Hz,1H,H-3'),5.43(t,J=9.2Hz,1H,H-3),5.33(t,J=9.2Hz,2H,H-2,H-2'),4.85(d,J=8.0Hz,1H,H-1'),4.60(d,J=9.6Hz,1H,H-1),4.54(d,J=12.0Hz,1H,PhCH2),4.46(d,J=12.0Hz,1H,PhCH2),4.14(dd,J=4.2,11.6Hz,1H),4.00(t,J=8.8Hz,H-4'),3.98(dd,J=4.0,11.2Hz,1H),3.88(t,J=9.6Hz,1H,H-4),3.84(d,J=4.0Hz,1H,OH),3.75-3.69(m,2H),3.67–3.60(m,2H),2.68–2.52(m,2H,SCH2),1.14(t,J=7.6Hz,3H,CH3),0.69(s,9H),-0.05(s,3H),-0.25(s,3H). 13 C NMR(150MHz,CDCl3)δ166.97,165.94,165.51,165.45,137.80,133.42,133.30,133.25,133.19,130.04,129.96,129.87,129.85,129.82,129.53,129.44,129.37,128.54,128.49,128.46,128.43,128.42,128.14,127.92,100.90,83.56,79.59,77.55,76.55,75.95,73.68,71.91,70.51,69.98,69.42,68.57,68.07,25.71,24.20,17.95,14.84,-4.12,-4.66.HRMS(ESI + ):calc.for C 55 H 62 NaO 14 SSi[M+Na] + 1029.3522,found:1029.3500.

[0149] Example 69: Trivalent iodine reagent participates in glycosylation to prepare compound III-17

[0150]

[0151] According to the standard operating procedure, donor I-30 (14.4 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-30 was completely converted, acceptor II-10 (13.3 mg, 0.043 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was complete, the white solid compound III-17 (30 mg, 93%) was obtained. 1 H NMR (400MHz, CDCl3) δ7.34 (2H, d, J = 8.4Hz Ar-CH),7.11(3H,m,J=8.0Hz,Ar-CH),5.64(1H,s,H-1),5.59(1H,d,J=3.2Hz,H-4),5.20(1H,ddd,J=3. 2,5.2,8.0Hz,H-3),5.17(1H,s,H-1′),4.28(1H,d,J=5.6Hz,H-2′),4.20(1H,dd,J=5.6,7.2Hz,H-3′),4 .08(2H,m,H-5,H-5′),3.54(1H,dd,J=7.2,9.6Hz,H-4′),3.13(3H,s),2.13(3H,s),2.07(1H,td,H-2a) ,1.97(3H,s),1.87(1H,dq,H-2b),1.51(3H,s),1.32(3H,s),1.19(3H,d,J=6Hz),1.10(3H,d,J=6.4Hz). 13 C NMR (100MHz, CDCl3) δ170.94,170.37,138.15,132.73,130.06,129.61,109.82,96.15,84.26,78.70,77.55,77. 23,76.91,76.84,69.96,66.81,65.73,65.31,30.19,28.16,26.74,21.34,21.15,20.99,18.15,16.70.HRMS(ESI + ):calc.for C 26 H 36 NaO9S[M+Na] + 547.1972, found: 547.1962.

[0152] Example 70: Trivalent iodine reagent participates in glycosylation to prepare compound III-18

[0153]

[0154] According to the standard operating procedure, donor I-13 (16.7 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuBr was added and after I-13 was completely converted, acceptor II-11 (19.5 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-18 (27.8 mg, 91%) was obtained. 1 H NMR (400MHz, CDCl3) δ7.33-7.22(15H,m,Ar-H),5.50(1H,dd,J=2.8,53.2Hz,H-1),5.13(1H,t,J=8.8,8.4Hz),4.94(3H,m),4.80(3H,m,PhCH 2), 4.67(1H,d,J=12.0Hz,PhCH2), 4.53(1H,d,J=10.8Hz,PhCH2), 4.48(1H,d,J=6.8Hz), 4.09(1H,dd,J=4.8,11.6Hz,H-6a), 4.00(1H,dd,J= 1.6,11.2Hz,H-6b),3.95(1H,t,J=9.2,9.6Hz),3.90(1H,m,H-5),3.76(1H,dd,J=3.6,11.2Hz,H-5a'),3.57(1H,t,J=9.6,10.0Hz),3.50(1H ,ddd,J=2.4,9.6,12.0Hz,H-2),3.29(1H,dd,J=8.8,11.6Hz,H-5b'),2.02(3H,s,CH3),2.02(3H,s,CH3),1.99(3H,s,CH3),1.92(3H,s,CH3). 13 C NMR (100MHz, CDCl3) δ170.33,170.00,169.46,138.58,138.07,137.76,128.78,128.64,128.32,128.26,128.19,128.10,127.94,106.77 ,100.61,81.48,79.51(d,J=20Hz),76.69,76.00,75.34,73.79,72.44,72.40,71.77,70.96,68.91,67.19,20.94,20.91,20.84.HRMS(ESI+ ):calc.for C 38 H 43 FNaO 12 [M+Na] + 733.2631, found: 733.2611.

[0155] Example 71: Trivalent iodine reagent participates in glycosylation to prepare compound III-19

[0156]

[0157] Compound S1 (350 mg, 1.68 mmol) was dissolved in DMF and placed in water at 0 °C. TIPSCl was added, and after the reaction was complete, the mixture was washed successively with saturated NH4Cl, water, and saturated NaCl. The organic phase was dried over anhydrous sodium sulfate, concentrated under vacuum, and purified by silica gel column chromatography to give a white solid S2 (507 mg, 83%). 1 H NMR (600MHz, CDCl3) δ4.45(d,J=3.5Hz,1H),4.31(d,J=9.7Hz,1H),4.27(d,J=1.9Hz,2H),3.68(t,J=9.3Hz,1H),3.52(td,J=10. 1,3.5Hz,1H),3.48(d,J=1.0Hz,1H),2.82–2.72(m,3H),2.58(s,1H),1.63(s,1H),1.31(t,J=7.4Hz,3H),1.05(d,J=3.9Hz,18H). 13 C NMR (150MHz, CDCl3) δ86.37,75.59,75.18,72.81,70.78,67.23,27.70,27.50,24.85,23.47,20.77,15.29.HRMS (ESI + ):calc.for C 17 H 36 NaO4SSi+[M+Na] + 387.1996, found: 387.1990.

[0158] Compound S2 (20 mg, 0.055 mmol) was dissolved in DMF and placed in water at 0 °C. NaH (6.6 mg, 0.16 mmol) and BnBr (28 mg, 0.16 mmol) were added, and the mixture was slowly heated to room temperature. After the reaction was complete, methanol was added to terminate the reaction. The mixture was extracted with ethyl acetate and washed successively with water and saturated NaCl. The organic phase was dried over anhydrous sodium sulfate, concentrated under vacuum, and purified by silica gel column chromatography to obtain colorless syrup I-31 (26 mg, 81%).1 H NMR (600MHz, CDCl3) δ7.40-7.37(6H,m,Ar-H),7.33(3H,m,Ar-H),7.28(1H,m,Ar-H),5.53(1H,d,J=5.4Hz,H-1),4 .96(1H,d,J=11.4Hz,PhCH2),4.70(1H,d,J=11.4Hz,PhCH2),4.64(1H,d,J=12.0Hz,PhCH2),4.11(1H,t,J=6.6Hz,H -3),3.96(1H,s,H-4),3.80(1H,m,H-5),3.80(1H,dd,J=6.6,10.2Hz),3.79(1H,dd,J=10.2,6.6Hz,H-6),2.66(1H, ddd,H-2a),2.53(2H,m,SCH2),1.99(1H,dd,J=4.2,13.2Hz,H-2b),1.27(3H,t,J=7.2Hz,CH3),1.07(21H,m,TIPS). 13 CNMR (150MHz, CDCl3) δ138.60,138.57,128.60,128.57,128.44,127.96,127.84,85.43,82.94, 77.65,75.96,75.17,71.12,70.20,67.60,27.79,27.76,25.41,23.56,20.82,15.27.HRMS(ESI + ):calc.for C 31 H 48 NaO4SSi + [M+Na] + 567.2935, found: 567.2924.

[0159]

[0160] According to the standard operating procedure, donor I-31 (47 mg, 0.086 mmol, 2.0 equivalent), trivalent iodine reagent IV-1 (43.2 mg, 0.13 mmol, 3.0 equivalent) and molecular sieve were added to the reaction flask. After CuCl was added and I-31 was completely converted, acceptor II-12 (18.0 mg, 0.043 mmol, 1.0 equivalent) and TfOH were added. After the reaction was completed, the white solid compound III-19 (36.0 mg, 93%) was obtained. 1H NMR (400MHz, CDCl3) δ7.75(d,J=7.6Hz,2H,Ar-H),7.58(d,J=7.2Hz,2H,Ar-H),7.38(t,J=7.6Hz,2H,Ar-H),7.30(m,12H,Ar-H),5.65(d,J=8.8Hz,1H,NH ),5.28(d,J=12.0Hz,1H,PhCH2),5.11(d,J=12.0Hz,1H,PhCH2),4.90(d,J=11.6Hz,1H,PhCH2),4.76(d,J=2.8Hz,1H,H-1),4.64(d,J=11.6Hz,1H,PhCH2 ),4.60–4.49(m,4H),4.42(dd,J=7.2,10.4Hz,1H,H-6a),4.32(dd,J=7.2,1 0.4Hz,1H),4.22(t,J=7.2Hz,1H),3.90(s,1H,H-4),3.85(t,J=4.0Hz,2H),3 .78(m,1H,H-5),3.70(m,2H),3.63(t,J=6.0Hz,1H),2.08(td,J=3.6,12.4H z,1H,H-2a),1.76(dd,J=4.0,12.8Hz,1H,H-2b),1.02–0.98(m,21H,OTIPS). 13 C NMR (100MHz, CDCl3) δ170.36,156.14,143.98,143.93,141.42,139.04,138.55 ,135.47,128.77,128.72,128.57,128.54,128.34,128.32,127.87,127.74,12 7.63,127.52,127.22,125.26,125.21,120.13,99.00,74.68,74.50,72.74,72 .44,70.55,68.28,67.42,62.77,54.55,47.26,30.95,18.11,11.98.HRMS(ESI + ):calc.for C 54 H 65 NNaO9Si[M+Na] + 922.4321, found: 922.4313.

[0161] Example 72: Trivalent iodine reagent participates in glycosylation to prepare compound III-20

[0162]

[0163] According to the standard operating procedure, donor I-37 (36.4 mg, 0.071 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (29.7 mg, 0.089 mmol, 1.5 equivalents), and molecular sieve were added to the reaction flask. After CuCl was added and I-37 was completely converted, acceptor II-13 (20 mg, 0.59 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrup compound III-20 (45.2 mg, 97%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.05(dd,J=1.2,8.4Hz,2H,Ar-H),8.00(dd,J=1.2,8.4Hz,2H,Ar-H),7.88(dd,J=1.2,7.8Hz,2H,Ar-H),7.56(m,1H,Ar-H),7.50(m,2H ,Ar-H),7.45(d,J=7.8Hz,2H,Ar-H),7.41(m,4H,Ar-H),7.31(m,10H,Ar-H),6 .85(d,J=8.4Hz,1H,Ar-H),6.79(d,J=1.8Hz,1H,Ar-H),6.68(dd,J=1.8,8.4H z,1H,Ar-H),5.83(dd,J=1.8,7.2Hz,1H,H-3),5.66(d,J=4.8Hz,1H,H-2),5.2 2(s,1H,H-1),5.12(s,2H,PhCH2),5.10(s,2H,PhCH2),4.70(m,1H,H-4),4.57 (dd,J=4.2,12.0Hz,1H,H-5a),4.41(dd,J=5.4,12.0Hz,1H,H-5b),3.92(dt,J =6.6,9.0Hz,OCH2),3.60(dt,J=7.2,9.0Hz,1H,OCH2),2.79–2.68(m,2H,CH2). 13C NMR (150MHz, CDCl3) δ166.25,165.51,165.39,149.10,147.73,137.65,137.54, 133.60,133.49,133.26,132.00,129.92,129.90,129.85,129.37,129.09,128.6 1,128.53,128.50,128.48,127.82,127.78,127.54,127.43,121.91,116.11,11 5.51,105.46,78.95,75.68,72.75,71.62,71.44,69.29,65.03,35.62.HRMS(ESI + ):calc.for C 48 H 42 NaO 10 [M+Na] + 801.2670, found: 801.2693.

[0164] Example 73: Trivalent iodine reagent participates in glycosylation to prepare compound III-21

[0165]

[0166] According to the standard operating procedure, donor I-21 (31.1 mg, 0.058 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (24.2 mg, 0.072 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-21 was completely converted, acceptor II-14 (20.0 mg, 0.048 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrup compound III-21 (39.5 mg, 92%) was obtained. 1H NMR (600MHz, CDCl3) δ7.36-7.27(13H,m,Ar-CH),7.22(2H,m,Ar-CH),7.16(1H,s,Ar-CH),6.47 (1H,s,Ar-CH),6.35(2H,s,Ar-CH),5.96(1H,d,J=1.2Hz),5.94(1H,d,J=1.2Hz),5.42(1H,dd,J =7.8,10.2Hz,H-2),4.93(1H,d,J=12.0Hz,PhCH2),4.87(1H,d,J=9.6H),4.67(1H,d,J=12.0Hz ,PhCH2),4.59(1H,d,J=11.4Hz,PhCH2),4.56-4.54(2H,m),4.50(1H,d,J=12.0Hz,PhCH2),4.41 (1H,d,J=9.6Hz,H-1),4.40(1H,d,J=11.4Hz,PhCH2),4.38(1H,d,J=12.0Hz,PhCH2),4.05(1H, dd,J=9.0,10.2Hz),3.93(1H,d,J=3.0Hz,H-4),3.78(3H,s,OCH3),3.73(6H,s,OCH3),3.61(1H, dd,J=6.0,9.0Hz,H-6a),3.56(1H,dd,J=6.0,9.0Hz,H-6b),3.52(1H,t,J=6.0Hz,H-5),3.49(1H ,dd,J=3.0,10.2Hz,H-3),2.89-2.83(1H,m),2.76(1H,dd,J=4.2,14.4Hz),2.00(3H,s,COCH3).

[0167] Example 74: Trivalent iodine reagent participates in glycosylation to prepare compound III-22

[0168]

[0169] Compound S3 (350 mg, 1.5 mmol) was dissolved in DMF, and then NaH (58.4 mg, 1.5 mmol) and allyl bromide (0.25 mL, 3.0 mmol) were added, followed by reflux. After the reactants were completely reacted, the organic phase was washed successively with saturated NaOH and saturated NaCl, dried over anhydrous Na2SO4, concentrated under vacuum, and then purified by silica gel column chromatography to give a yellow oily liquid S4 (364 mg, 89%). 1H NMR (600MHz, CDCl3) δ7.45(2H,d,J=7.8Hz,Ar-H),7.41(2H,t,J=7.8Hz,Ar-H),7.35(1H,t,J=7.2Hz,Ar-H),6.70( 2H,s,Ar-H),6.02(2H,m,CH),5.18(4H,m,CH2),5.02(2H,s,PhCH2),4.80(1H,s,OH),3.40(4H,d,J=6.6Hz,ArCH2). 13 CNMR(150MHz, CDCl3)δ152.81,146.79,137.49,136.51,128.65,128.00,127.71,126.98,116.62,115.07,70.73,35.60.HRMS(ESI + ):calc.for C 19 H 20 NaO2[M+Na] + 303.1356, found: 303.1350.

[0170] Compound S4 (100 mg, 0.36 mmol) was dissolved in DCM, and then 2-methyl-2-butene (1.9 mL, 17.8 mmol) and a second-generation Grubbs catalyst (30.3 mg, 0.04 mmol) were added, followed by reflux. After the starting material was completely reacted, the mixture was concentrated under vacuum and then purified by silica gel column chromatography to obtain II-15 (96 mg, 80%). 1 H NMR(600MHz, CDCl3) δ7.42(dd,J=0.8,8.4Hz,2H,Ar-H),7.37(m,2H,Ar-H),7.31(m,1H,Ar-H),6.63(s,2H,Ar-H),5.2 9(m,2H,CH),4.98(s,2H,PhCH2),4.95(s,1H,OH),3.31(d,J=7.2Hz,4H,CH2),1.76(s,3H),1.75(s,3H),1.74(s,6H). 13 C NMR (150MHz, CDCl3) δ152.59,146.84,137.66,134.53,128.66,128.29,127.95,127.71,122.01,114.20,70.73,29.93,25.95,17.99.

[0171]

[0172] According to the standard operating procedure, donor I-08 (15.4 mg, 0.039 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (16.5 mg, 0.050 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-08 was completely converted, acceptor II-15 (11 mg, 0.033 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-22 (20.7 mg, 94%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.43(m,2H,Ar-H),7.40(m,2H,Ar-H),7.34(m,1H),6.63(s,2H),6.63(s,2H,Ar-H),5.35(dd,J=7.8,9.0Hz,1H,H-2 ),5.26(t,J=9.6Hz,1H,H-3),5.22(m,2H,CH),5.21(t,J=9.6Hz,1H,H-4),5.00(s,2H,PhCH2),4.81(d,J=7.8Hz,1H),4.81(d,J=8.0Hz,1 H),4.23(dd,J=12.3,4.3Hz,1H),4.22(dd,J=4.2,12.0Hz,1H,H-6a),4.09(dd,J=2.4,12.0Hz,1H,H-6b),3.58(m,1H,H-5),3.42(dd,J=7 .8,15.6Hz,2H,Ar-CH2),3.34(dd,J=6.6,16.2Hz,ArCH2),2.11(s,3H),2.06(s,3H),2.05(s,3H),2.04(s,3H),1.76(s,6H),1.70(s,6H). 13 C NMR (150MHz, CDCl3) δ170.76,170.52,169.54,169.44,155.96,145.65,137.28,136.37,133.05,128.69,128.08,127.77,127.75 ,122.66,113.57,102.23,73.21,71.91,71.78,70.29,68.45,61.81,28.73,25.87,20.83,20.78,20.75,20.73,17.97.HRMS(ESI + ):calc.for C 37 H 46 NaO 11 [M+Na] + 689.2932, found: 689.2922.

[0173] Example 75: Trivalent iodine reagent participates in glycosylation to prepare compound III-23

[0174]

[0175] According to the standard operating procedure, donor I-33 (30 mg, 0.029 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (38.4 mg, 0.116 mol, 4.0 equivalent) and molecular sieve were added to the reaction flask. After CuCl was added and I-33 was completely converted, acceptor II-16 (17.0 mg, 0.057 mmol, 2.0 equivalent) and BF3·Et2O were added. After the reaction was complete, a white solid compound III-23 (34.5 mg, 94%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.02(d,J=7.8Hz,2H),7.98(d,J=8.4Hz,2H),7.80(d,J=7.8Hz,2H),7.58(t,J=7.2Hz,1H),7.49(t,J=7.2Hz,1H),7.39-7.0 7(m,31H),5.99(dd,J=9.6,3.0Hz,1H),5.79(s,1H),5.70(s,1H),5.44( s,1H),5.36(s,1H),4.98(d,J=7.8Hz,1H),4.80(d,J=10.8Hz,1H),4.73( t,J=10.2Hz,1H),4.63(m,J=12.0Hz,2H),4.57(d,J=11.6Hz,2H),4.49- 4.44(m,2H),4.38(d,J=12.0Hz,1H),4.31(d,J=10.8Hz,1H),4.11-4.08( m,1H),4.04-3.96(m,3H),3.90-3.88(m,1H),3.80-3.75(m,2H),3.71(s ,3H),3.59(d,J=10.8Hz,1H),3.06(qd,J=13.8,5.4Hz,2H),1.44(s,9H).

[0176] Example 76: Trivalent iodine reagent participates in glycosylation to prepare compound III-24

[0177]

[0178] According to the standard operating procedure, donor I-26 (31.1 mg, 0.052 mmol, 1.0 equivalent), trivalent iodine reagent IV-3 (21.6 mg, 0.065 mmol, 1.5 equivalent) and molecular sieve were added to the reaction flask. CuCl was added and after I-26 was completely converted, acceptor II-17 (16.7 mg, 0.104 mmol, 2.0 equivalent) and TfOH·DTBP were added. After the reaction was completed, the white solid compound III-24 (27.5 mg, 76%) was obtained. 1 H NMR(600MHz, CDCl3)δ9.45(s,1H,OH),7.90-7.88(m,2H,Ar-H),7.57-7.54(m,1H,Ar-H),7.46–7.4 3(m,3H,Ar-H),7.41–7.37(m,5H,Ar-H),7.36-7.30(m,10H,Ar-H),7.20-7.16(m,3H,Ar-H),7.00( t,J=6.4Hz,1H,Ar-H),6.95(d,J=7.8Hz,Ar-H),5.51(d,J=3.6Hz,1H,H-1),5.05(d,J=11.4Hz,1H, PhCH2),5.00(d,J=11.4Hz,1H,PhCH2),4.91(d,J=12.0Hz,1H,PhCH2),4.85(d,J=11.4Hz,1H,PhCH 2) ,4.77(d,J=12.6Hz,1H,PhCH2),4.69(d,J=11.4Hz,1H,PhCH2),4.49(dd,J=6.6,9.6Hz),4.30( dd,J=3.6,9.6Hz,1H),4.27-4.23(m,2H),4.14(dd,J=3.0,10.2Hz,H-2),3.97(d,J=2.4Hz,1H). 13 C NMR (150MHz, CDCl3) δ165.99,154.17,154.02,138.25,137.84,137.47,136.67,13 3.12,129.68,129.63,129.62,128.56,128.49,128.46,128.45,128.34,128.21,1 28.01,127.98,127.83,127.77,127.62,125.71,123.31,118.96,115.75,111.21, 109.74,99.31,79.10,75.88,74.76,74.46,74.14,73.85,69.90,63.90.HRMS(ESI +):calc.for C 44 H 40 NaO8[M+Na] + 719.2615, found: 719.2627.

[0179] Example 77: Trivalent iodine reagent participates in glycosylation to prepare compound III-25

[0180]

[0181] According to the standard operating procedure, donor I-02 (28.7 mg, 0.086 mmol, 2.0 equivalent), trivalent iodine reagent IV-1 (43.1 mg, 0.129 mmol, 3.0 equivalent) and molecular sieve were added to the reaction flask. After CuCl was added and I-02 was completely converted, acceptor II-18 (17.7 mg, 0.043 mmol, 1.0 equivalent) and TfOH were added. After the reaction was completed, the white solid compound III-25 (21.8 mg, 74%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.85(m,2H,Ar-H),7.24(m,2H,Ar-H),7.13(d,J=2.4Hz,1H, Ar-H),6.81(d,J=1.8Hz,1H),5.92(dd,J=0.6,3.0Hz,1H,H-2),5.28(d,J=0.6Hz,1 H,H-1),5.16(dd,J=3.6,10.2Hz,1H,H-3),5.12(t,J=9.0Hz,1H,H-4),3.58(m,1H ,H-5),2.34(s,3H),2.34(s,3H),2.33(s,3H),2.29(s,3H),1.29(d,J=6.0Hz,3H). 13 C NMR (150MHz, CDCl3) δ170.51,170.01,169.90,169.75,168.92,168.09,167.94,157.29,156.18,154.09,153.53,152.74,134. 23,129.53,127.16,122.01,113.96,106.52,97.45,70.86,70.78,70.67,68.67,20.99,20.81,20.69,20.64,17.42.HRMS (ESI + ):calc.for C 33 H 32 NaO 16 [M+Na] +707.1583, found: 707.1574.

[0182] Example 78: Trivalent iodine reagent participates in glycosylation to prepare compound III-26

[0183]

[0184] According to the standard operating procedure, donor I-39 (20 mg, 0.046 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (23.2 mg, 0.069 mol, 1.5 equivalent), and molecular sieve were added to a reaction flask. CuCl was added, and after I-39 was completely converted, acceptor II-19 (18.6 mg, 0.092 mmol, 2.0 equivalent) and TfOH·DTBP were added. After the reaction was complete, the product was processed to obtain a colorless syrupy compound III-26 (20.5 mg, 93%). Data for the α-configuration product III-26 are available. 1 H NMR(600MHz CD3COCD3): δ8.38-8.34(m,2H,-Ph),8.22(d,J=7.6Hz,1H,-Ph),8.18-8.15(m,2H,-Ph),7.57-7.39(m,2H,-Ph),7.43-7.39(m,1H,-Ph),6.75(s,1 H,-NH),6.38(d,J=3.6Hz,1H,H-1),4.67(d,J=10.0Hz,1H,H-4),4.39(dq,J=6.4,10.0Hz,1H,H-5),2.81(dd,J=1.2,15.2Hz,1H,H-2a,overlapped with Data for β-configuration product III-26: 2.51 (t, J = 7.2 Hz, 2H), 2.14 (dd, J = 3.6, 15.2 Hz, 1H, H-2b), 2.11 (s, 3H, COCH3), 1.67-1.60 (m, 2H), 1.57-1.51 (m, 2H), 1.20 (s, 3H, -CH3-C3), 1.09 (d, J = 6.4 Hz, 3H, H-6), 0.96 (t, J = 7.6 Hz, 3H, -Me). 1H NMR (600MHzCD3COCD3): δ8.45-8.43(m,2H,Ph),8.27(m,2H,-Ph),7.86(d,J=7.8Hz,1H,-Ph),7.58-7.53(m,2H,-Ph), 7.45-7.42(m,1H,-Ph),6.73(s,1H,-NH),6.38(d,J=1.8,10.2Hz,1H,H-1),5.04(m,1H,H-5),4.61(d,J=10.2Hz,1H,H- 4),2.85(dd,J=1.8,13.8Hz,1H,H-2a),2.51(t,J=7.2Hz,2H),2.14(s,3H,COCH3),1.94(dd,J=10.2,13.8Hz,1H,H-2b ),1.66-1.61(m,2H),1.55-1.49(m,2H),1.25(s,3H,-CH3-C3),1.25(d,J=6.6Hz,3H,H-6),0.96(t,J=7.8Hz,3H,-Me).

[0185] Example 79: Trivalent iodine reagent participates in glycosylation to prepare compound III-27

[0186]

[0187] According to the standard operating procedure, donor I-27 (28.0 mg, 0.048 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (20.0 mg, 0.06 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-27 was completely converted, acceptor II-20 (10 mg, 0.04 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was complete, the colorless syrupy compound III-27 (28.6 mg, 92%) was obtained. 1H NMR (600MHz, CDCl3) δ7.33–7.26(m,20H),7.25–7.19(m,6H),7.15–7.11(m,4H),6.06(dd,J=6.6,3.0 Hz,1H),4.89(d,J=10.8Hz,1H),4.80(d,J=10.8Hz,1H),4.78–4.73(m,2H),4.63(d,J=11.4Hz,1H),4 .54(d,J=12.0Hz,1H),4.48(d,J=10.8Hz,1H),4.42(d,J=12.0Hz,1H),3.88(t,J=9.0Hz,1H),3.77(d t,J=10.2,2.4Hz,1H),3.72(dd,J=10.2,9.0Hz,1H),3.65–3.61(m,2H),3.35(dd,J=10.8,1.8Hz,1H).

[0188] Example 80: Trivalent iodine reagent participates in glycosylation to prepare compound III-28

[0189]

[0190] According to the standard operating procedure, donor I-36 (20 mg, 0.063 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (27.1 mg, 0.081 mmol, 1.3 equivalent), and molecular sieve were added to the reaction flask. CuCl was added until I-36 was completely converted. Acceptor II-21 (32.0 mg, 0.125 mmol, 2.0 equivalent) and BSTFA (0.13 mL, 0.500 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, the colorless syrupy compound III-28 (21.9 mg, 95%) was obtained after processing. 1 H NMR (600MHz, CDCl3) δ9.40 (s, 1H, NH), 7.39 (d, J = 8.4Hz, 1H), 6.03 (d, J = 4.8Hz, 1H), 5.78 (d, J = 8.4Hz, 1H ),5.34-5.31(m,2H),4.36–4.31(m,3H),2.13(s,3H,-COCH3),2.12(s,3H,-COCH3),2.09(s,3H,-COCH3).

[0191] Example 81: Trivalent iodine reagent participates in glycosylation to prepare compound III-29

[0192]

[0193] According to the standard operating procedure, donor I-38 (20 mg, 0.076 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (38.2 mg, 0.11 mmol, 1.5 equivalent), and molecular sieve were added to the reaction flask. CuCl was added until I-38 was completely converted. Acceptor II-22 (41.8 mg, 0.15 mmol, 2.0 equivalent) and BSTFA (0.15 mL, 0.6 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, the colorless syrupy compound III-29 (23.9 mg, 95%) was obtained after processing. 1 H NMR (600MHz, CDCl3) δ9.61(brs,1H),7.36(d,J=5.4Hz,1H),5.94(d,J=4.8Hz,1H),5.29(t,J=5.4H z,1H),5.01(t,J=5.4Hz,1H),4.24–4.19(m,1H),2.11(s,3H),2.09(s,3H),1.45(d,J=6.6Hz,3H).

[0194] Example 82: Trivalent iodine reagent participates in glycosylation to prepare compound III-30

[0195]

[0196] According to the standard operating procedure, donor I-08 (20 mg, 0.051 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (22.1 mg, 0.066 mmol, 1.3 equivalent), and molecular sieve were added to the reaction flask. CuCl was added until I-08 was completely converted. Acceptor II-23 (39.0 mg, 0.10 mmol, 2.0 equivalent) and BSTFA (0.10 mL, 0.4 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, a colorless syrupy compound III-30 (28.0 mg, 97%) was obtained after processing. 1H NMR(600MHz, CDCl3)δ9.10(brs,1H,NH),7.78(s,1H),5.87(d,J=9.6Hz,1H,H-1) ,5.42(t,J=9.6Hz,1H),5.20–5.16(m,2H),4.29(dd,J=12.6,5.2Hz,1H,H-6a),4 .17(dd,J=12.6,2.4Hz,1H,H-6b),3.97(ddd,J=10.2,5.2,1.8Hz,1H,H-5),2.13 (s,3H,-COCH3),2.08(s,3H,-COCH3),2.04(s,3H,-COCH3),2.03(s,3H,-COCH3).

[0197] Example 83: Trivalent iodine reagent participates in glycosylation to prepare compound III-31

[0198]

[0199] According to the standard operating procedure, donor I-09 (30 mg, 0.047 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (20.3 mg, 0.070 mmol, 1.3 equivalent), and molecular sieve were added to the reaction flask. CuCl was added until I-09 was completely converted. Acceptor II-24 (25.3 mg, 0.094 mmol, 2.0 equivalent) and BSTFA (0.10 mL, 0.376 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, a white solid compound III-31 (31.3 mg, 95%) was obtained after processing. 1 H NMR (600MHz, CDCl3) δ8.51(s,1H,NH),8.05–7.26(m,21H),6.26(d,J=9.6Hz,1H,H-1),6.08(t,J=9.6Hz,1H),5.78(t,J=9.6Hz,1H),5.68(t,J=9.6H z,1H),4.67(dd,J=12.6,2.8Hz,1H,H-6a),4.49(dd,J=12.6,5.2Hz,1H,H-6b),4.40(ddd,J=10.0,5.2,2.8Hz,1H,H-5),1.93(d,J=1.2Hz,3H,CH3).

[0200] Example 84: Trivalent iodine reagent participates in glycosylation to prepare compound III-32

[0201]

[0202] According to the standard operating procedure, donor I-25 (30 mg, 0.070 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (30.0 mg, 0.091 mmol, 1.3 equivalent), and molecular sieve were added to the reaction flask. CuCl was added until I-25 was completely converted. Acceptor II-25 (45.2 mg, 0.139 mmol, 2.0 equivalent) and BSTFA (0.14 mL, 0.556 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, the colorless syrupy compound III-32 (37.1 mg, 97%) was obtained after processing. 1 H NMR(600MHz, CDCl3)δ8.40(brs,1H),7.91(s,1H),7.38–7.31(m,6H),7.30–7.26(m,4H),6.27 (d,J=9.6Hz,1H,H-1),5.23(dd,J=9.6,3.0Hz,1H,H-2),4.63(d,J=12.0Hz,1H,-CH2Ph),4.55( d,J=12.0Hz,1H,-CH2Ph),4.52(s,2H,2×-CH2Ph),4.34(q,J=7.2Hz,1H,H-5),4.07(t,J=3.0Hz ,1H,H-3),3.45(dd,J=3.6,1.2Hz,1H,H-4),2.02(s,3H,-COCH3),1.48(d,J=7.2Hz,3H,-CH3).

[0203] Example 85: Trivalent iodine reagent participates in glycosylation to prepare compound III-33

[0204]

[0205] According to the standard operating procedure, I-02 (20 mg, 0.060 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (26.0 mg, 0.078 mmol, 1.3 equivalent), and molecular sieve were added to the reaction flask. CuCl was added and the I-02 was completely converted. Acceptor II-26 (34.4 mg, 0.120 mmol, 2.0 equivalent) and BSTFA (0.12 mL, 0.48 mmol, 8.0 equivalent) were stirred in acetonitrile for 30 min and then added to the donor reaction flask. TfOH was then added. After the reaction was complete, the colorless syrupy compound III-33 (24.0 mg, 82%) was obtained after processing. 1H NMR (600MHz, CDCl3) δ8.69(s,1H,NH),7.93–7.81(m,3H),7.63–7.49(m,4H),6.46(d,J=9.6Hz,1H),5.45(t,J=3.6Hz,1H),5.30(dd,J=9.6,3.6Hz,1H) ,4.86(dd,J=3.6,1.2Hz,1H),4.32(q,J=7.2Hz,1H,H-5),2.21(s,3H,-COCH3),2.19(s,3H,-COCH3),1.96(s,3H,-COCH3),1.58(d,J=7.2Hz,3H,-CH3).

[0206] Example 86: Trivalent iodine reagent participates in glycosylation to prepare compound III-34

[0207]

[0208] According to the standard operating procedure, donor I-22 (42.8 mg, 0.071 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (29.7 mg, 0.089 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-22 was completely converted, acceptor II-27 (20 mg, 0.059 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-34 (43.1 mg, 83%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.70 (s, 1H), 8.42 (s, 1H), 7.73 (d, J = 7.2Hz, 2H), 7.49–7.46 (m, 1H), 7.39–7. 27(m,12H),7.24–7.16(m,5H),6.10(t,J=9.6Hz,1H),5.96(d,J=9.6Hz,1H),5.05(d,J=11.4Hz,1H ),4.68(dd,J=12.0,5.4Hz,2H),4.55(d,J=12.0Hz,1H),4.47(q,J=12.0Hz,2H),4.17(d,J=1.8Hz, 1H), 3.96 (t, J=6.6Hz, 1H), 3.92 (dd, J=9.6, 2.4Hz, 1H), 3.66 (qd, J=9.6, 6.6Hz, 2H), 1.29 (s, 18H).

[0209] Example 87: Trivalent iodine reagent participates in glycosylation to prepare compound III-35

[0210]

[0211] According to the standard operating procedure, donor I-09 (40.7 mg, 0.063 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (26.5 mg, 0.079 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-09 was completely converted, acceptor II-28 (10.0 mg, 0.053 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-35 (32.1 mg, 79%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.47(s,1H),8.02(dd,J=8.4,1.2Hz,2H),7.94(dd,J=8.4,1.2Hz,2H),7.82(dd,J=8.4,1.2Hz,2H),7.74(dd,J=8.4,1.2Hz,2H),7. 58–7.26(m,12H),6.27(d,J=9.6Hz,1H,H-1),6.17(t,J=9.6Hz,1H),6.03(t ,J=9.6Hz,1H),5.90(t,J=9.6Hz,1H),4.71–4.67(m,1H),4.55–4.51(m,2H).

[0212] Example 88: Trivalent iodine reagent participates in glycosylation to prepare compound III-36

[0213]

[0214] According to the standard operating procedure, donor I-25 (43.0 mg, 0.099 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (41.6 mg, 0.124 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-25 was completely converted, acceptor II-29 (15 mg, 0.083 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, a white solid compound III-36 (43.2 mg, 95%) was obtained. 1H NMR (400MHz, CDCl3) δ7.78 (s, 1H, CH), 7.37–7.25 (m, 10H, Ar-H), 6.62 (d, J = 8.4Hz, 1H, H-1), 5.70 (dd, J = 8 .4,3.2Hz,1H,H-2),4.63(d,J=12.0Hz,1H,-CH2Ph),4.59(d,J=12.0Hz,1H,-CH2Ph),4.55(d,J=12.0Hz,1 H,-CH2Ph),4.51(d,J=12.0Hz,1H,-CH2Ph),4.18–4.10(m,1H,H-5),4.03(t,J=3.6Hz,1H,H-3),3.57(s,3 H,-CH3),3.48(t,J=4.0Hz,1H,H-4),3.40(s,3H,-CH3),1.93(s,3H,-COCH3),1.48(d,J=6.8Hz,3H,-CH3). 13 C NMR (100MHz, CDCl3) δ169.7,154.9,151.7,148.9,139.9,137.5,137.4,128.7,128.2,128.2 ,128.2,128.0,106.9,77.7,75.8,73.7,73.3,72.6,69.5,30.0,28.2,20.8,17.1.HRMS(ESI + ):calc.for C 29 H 32 N4NaO7[M+Na] + 571.2163, found: 571.2155.

[0215] Example 89: Trivalent iodine reagent participates in glycosylation to prepare compound III-37

[0216]

[0217] According to the standard operating procedure, donor I-22 (60.8 mg, 0.102 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (42.4 mg, 0.127 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-22 was completely converted, acceptor II-30 (5.0 mg, 0.085 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-37 (47.1 mg, 93%) was obtained. 1H NMR (600MHz, CDCl3) δ8.00–7.96(m,2H,Ar-H),7.60(t,J=7.2Hz,1H,Ar-H),7.45(t,J=7.8Hz,2H,Ar-H),7.37–7.27(m,10H,Ar-H),7. 25–7.19(m,5H,Ar-H),6.46–6.42(m,1H,NH),5.52(t,J=9.6Hz,1H,H-2),5.21(t,J=9.6Hz,1H,H-1),4.96(d,J=11.4Hz,1H,-CH2Ph),4 .67(d,J=12.0Hz,1H,-CH2Ph),4.63(d,J=11.4Hz,1H,-CH2Ph),4.56(d,J=12.0Hz,1H,-CH2Ph),4.48(d,J=12.0Hz,1H,-CH2Ph),4.44( d,J=12.0Hz,1H,-CH2Ph),4.10(d,J=2.4Hz,1H,H-4),3.81–3.77(m,2H,H-3,H-5),3.66–3.60(m,2H,H-6a,H-6b),1.87(s,3H,COCH3).

[0218] Example 90: Trivalent iodine reagent participates in glycosylation to prepare compound III-38

[0219]

[0220] According to the standard operating procedure, donor I-08 (43.3 mg, 0.110 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (46.0 mg, 0.138 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-08 was completely converted, acceptor II-31 (8.0 mg, 0.092 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-38 (33.7 mg, 88%) was obtained. 1 H NMR (600MHz, CDCl3) δ6.08(s,1H,NH),5.81(d,J=5.2Hz,1H,H-1),5.19(t,J=3.0Hz,1H,H-3),4.88(dd,J=9.6,2.8Hz,1H,H-4),4.46–4.43(m,1H ,H-2),4.21–4.16(m,2H,H-6a,H-6b),3.98–3.95(m,1H,H-5),2.10–2.0 5(m,11H),1.90(s,3H,-CH3),1.65–1.59(m,2H),0.92(t,J=7.2Hz,3H).13 C NMR (150MHz, CDCl3) δ172.2,170.7,169.7,169.2,110.5,97.9,74.2,70.2,68.1,67.3,63.1,38.9,24.7,20.8,20.8,20.8,18.7,13.6.HRMS (ESI + ):calc.for C 18 H 27 NO 10 [M+Na] + 440.1527, found: 440.1542.

[0221] Example 91: Trivalent iodine reagent participates in glycosylation to prepare compound III-39

[0222]

[0223] According to the standard operating procedure, donor I-19 (29.3 mg, 0.049 mmol, 1.5 equivalents), trivalent iodine reagent IV-1 (24.0 mg, 0.072 mmol, 2.2 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-19 was completely converted, acceptor II-32 (10.0 mg, 0.033 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-39 (25.8 mg, 94%) was obtained. 1H NMR (400MHz, CDCl3) δ7.96(d,J=7.2Hz,2H),7.56(t,J=7.2Hz,1H),7.41(t,J=7.6Hz,2H),7.37–7.25(m,13H),7.18–7.06(m,7H),6.51(d, J=8.8Hz,1H),5.90(d,J=8.8Hz,1H),5.61–5.51(m,1H),5.21(t,J=9.2Hz,1H),5.15–5.02(m,4H),4.98(d,J=10.4Hz,1H),4.77(d,J=10.8 ,1H),4.76(d,J=10.8,1H),4.70(d,J=11.2Hz,1H),4.64(d,J=12.0Hz,1H),4.55–4.43(m,3H),4.33(dd,J=13.2,5.6Hz,1H),4.18(dd,J=1 3.2,5.6Hz,1H),3.92–3.81(m,2H),3.79–3.71(m,2H),3.57(d,J=9.2Hz,1H),2.84(dd,J=16.4,4.2Hz,1H),2.68(dd,J=16.4,4.2Hz,1H).

[0224] Example 92: Trivalent iodine reagent participates in glycosylation to prepare compound III-40

[0225]

[0226] According to the standard operating procedure, donor I-08 (20.3 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-08 was completely converted, acceptor II-33 (8.4 mg, 0.043 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was complete, the colorless syrupy compound III-40 (16.1 mg, 71%) was obtained. 1 H NMR (CDCl3, 600MHz) δ: 8.37 (1H, s), 7.90 (1H, s), 6.02 (1H, d, J = 5.4Hz), 5.22 (1H, t, J = 3.0Hz), 4.92 (1H, dd, J = 2 ,4,9.6Hz),4.70(1H,dd,J=3.0,4.8Hz),4.23(2H,m),4.04(3H,s),4.02-3.99(1H,m),2.11(6H,m),2.03(3H,s).

[0227] Example 93: Trivalent iodine reagent participates in glycosylation to prepare compound III-41

[0228]

[0229] According to the standard operating procedure, donor I-24 (42.0 mg, 0.071 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (29.3 mg, 0.088 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-24 was completely converted, acceptor II-34 (10.0 mg, 0.058 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, a white foamy compound III-41 (38.8 mg, 92%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.03(d,J=7.8Hz,2H,Ar-H),7.78(d,J=7.8Hz,2H,Ar-H),7.56(t,J=7.2Hz,1H,Ar-H),7.38–7.15(m,19H,Ar-H),5.79 (d,J=8.4Hz,1H,NH),5.63(d,J=3.0Hz,1H,H-2),5.46(dd,J=7.8,3.0Hz,1H),4.72(t,J=12.0Hz,2H,2×-CH2Ph),4.59(d,J=12.0Hz,1H,-CH2 Ph),4.50(d,J=11.4Hz,1H,-CH2Ph),4.47(d,J=10.8Hz,1H,-CH2Ph),4.43(d,J=12.0Hz,1H,-CH2Ph),4.01(t,J=8.4Hz,1H,H-4),3.91–3.8 7(m,1H,H-3),3.65(dd,J=10.8,3.6Hz,1H,H-6a),3.52–3.48(m,1H,H-5),3.22–3.16(m,1H,H-6b),2.34(s,3H,CH3).HRMS(ESI+):calc.for C41H41NO8[M+Na] + 730.2445, found: 730.2427.

[0230] Example 94: Trivalent iodine reagent participates in glycosylation to prepare compound III-42

[0231]

[0232] According to the standard operating procedure, donor I-24 (31.1 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.064 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-24 was completely converted, acceptor II-35 (8.7 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was complete, the colorless syrupy compound III-42 (29.2 mg, 92%) was obtained. 1 H NMR (400MHz, CDCl3) δ8.09–7.94(m,6H,Ar-H),7.58(t,J=7.4Hz,1H,Ar-H),7.41–7.22(m,15H,Ar-H),7.19–7.12(m,2H,Ar-H),6.27(br s,1H),5.54(d,J=6.0Hz,2H),4.72–4.60(m,2H),4.57–4.41(m,4H),3.96–3.80(m,2H),3.79–3.67(m,2H),3.32(dd,J=9.6,2.0Hz,1H). 13 C NMR (100MHz, CDCl3) δ165.9,150.0,146.7,137.9,137.5,137.4,133.8,130.1,129.2,128.8,128.7,12 8.6,128.2,128.1,128.0,127.9,124.2,79.2,76.6,74.1,73.9,73.9,73.6,72.6,69.1,68.0.HRMS(ESI + ):calc.forC 41 H 41 NNaO8[M+Na] + 761.2139, found: 761.2136.

[0233] Example 95: Trivalent iodine reagent participates in glycosylation to prepare compound III-43

[0234]

[0235] According to the standard operating procedure, donor I-22 (31.1 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.064 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-22 was completely converted, acceptor II-36 (10.2 mg, 0.043 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the white solid compound III-43 (32.2 mg, 97%) was obtained. 1 H NMR(600MHz, CDCl3)δ8.00(s,2H),7.66(t,J=7.2Hz,1H),7.52(t,J=7.8Hz,2H),7.42–7.14(m,25H),5.3– 5.29(m,2H,NH,H-2),5.09(t,J=9.0Hz,1H,H-1),4.89(d,J=11.4Hz,1H,PhCH2),4.61(d,J=11.4Hz,1H,Ph CH2),4.60(d,J=11.4Hz,1H,PhCH2),4.51(d,J=12.0Hz,1H,PhCH2),4.45(d,J=12.0Hz,1H,PhCH2),4.4 3(d,J=12.0Hz,1H,PhCH2),4.05(d,J=2.4Hz,1H,H-4),3.73–3.68(m,2H,H-3,H-5),3.65–3.58(m,2H). 13 CNMR (150MHz, CDCl3) δ166.2,155.3,138.4,137.9,137.8,133.4,130.1,129.8,129.5,128.7,128.6,128.5,12 8.4,128.4,128.1,127.9,127.8,127.8,127.7,81.0,80.3,75.1,74.9,73.6,73.3,72.2,71.3,67.8.HRMS(ESI + ):calc.for C 49 H 44 N₂O₇[M+Na] + 795.3041, found: 795.3021.

[0236] Example 96: Trivalent iodine reagent participates in glycosylation to prepare compound III-44

[0237]

[0238] According to the standard operating procedure, donor I-23 (26.1 mg, 0.049 mmol, 2.0 equivalent), trivalent iodine reagent IV-1 (24.4 mg, 0.073 mmol, 3.0 equivalent) and molecular sieve were added to the reaction flask. After CuCl was added and I-23 was completely converted, acceptor II-37 (10.0 mg, 0.024 mmol, 1.0 equivalent) and Ph3CB(C6F5)4 were added. After the reaction was completed, the colorless syrupy compound III-44 (18.2 mg, 85%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.37–7.24(m,23H,Ar-H),7.18–7.16(m,2H,Ar-H),5.85(d,J=9. 0Hz,1H,H-1),5.17(d,J=12.0Hz,1H),5.12–5.00(m,4H),4.55–4.45(m,5H),4.40(t,J =12.4Hz,2H),4.17-4.10(m,3H),4.04(dd,J=10.8,3.0Hz,1H),3.82(dd,J=10.4,7.2H z,1H),3.68–3.65(m,1H),3.64(s,3H,COOCH3),3.63–3.60(m,1H),2.01(s,3H,COCH3).

[0239] Example 97: Trivalent iodine reagent participates in glycosylation to prepare compound III-45

[0240]

[0241] According to the standard operating procedure, donor I-19 (33.0 mg, 0.055 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (23.0 mg, 0.069 mol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-19 was completely converted, acceptor II-38 (15.0 mg, 0.046 mmol, 1.0 equivalents) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-45 (34.9 mg, 88%) was obtained. 1H NMR(600MHz,CDCl3)δ:7.92(d,J=7.2Hz,2H,Ar-H),7.69(t,J=7.2Hz,2H,Ar-H),7.55(d,J=7.2Hz,2H,Ar-H),7.42(m,4H,Ar-H),7.37(t,J=7.2Hz,2H,Ar-H),7.34-7.25(m,7H,Ar-H),7.14(dd,J=1.2,7.2Hz,1H,Ar-H),7.10-7.04(m,6H,Ar-H),7.00(d,J=3.6Hz,1H,Ar-H),6.84(dd,J=3.0,9.0Hz,1H,Ar-H),5.48(t,J=9.0,9.6Hz,1H,H-2),5.03(d,J=9.0Hz,H-1),4.85(d,J=10.8Hz,1H,PhCH2),4.73(d,J=12.0Hz,1H,PhCH2),4.67(m,2H,PhCH2),4.64(d,J=10.8Hz,1H,PhCH2),4.57(d,J=10.8Hz,1H,PhCH2),3.95(m,2H,H-6a,H-3),3.87(dd,J=5.4,10.2Hz,1H,H-6b),3.82(t,J=9.0Hz,1H,H-4),3.73(m,1H,H-5),3.08(s,2H),2.67(s,2H),2.21(s,4H),2.16(s,3H). 13 C NMR(150MHz,CDCl3)δ164.25,160.87,153.64,146.07,138.49,138.12,137.89,137.44,133.06,132.03,130.84,130.34,129.98,129.32,128.62,128.56,128.31,128.23,128.05,127.77,127.69,127.50,126.12,125.97,125.26,124.96,123.41,122.98,91.26,84.21,78.48,76.53,75.27,73.50,69.54,55.05,46.13,29.85.HRMS(ESI + ):calc.forC 52 H 51 ClN4NaO6[M+Na] + 885.3389,found:885.3372.

[0242] Example 98: Trivalent iodine reagent participates in glycosylation to prepare compound III-46

[0243]

[0244] According to the standard operating procedure, donor I-31 (46.9 mg, 0.086 mmol, 2.0 equivalent), trivalent iodine reagent IV-1 (43.1 mg, 0.13 mol, 3.0 equivalent) and molecular sieve were added to the reaction flask. CuCl was added and after I-31 was completely converted, acceptor II-44 (5.6 mg, 0.043 mmol, 1.0 equivalent) and TfOH·DTBP were added. After the reaction was completed, the white solid compound III-46 (16.5 mg, 83%) was obtained. 1 H NMR (600MHz, CDCl3) δ7.52(d,J=7.2Hz,1H,Ar-H),7.45-7.42(m,3H,Ar-H),7.37-7.34(m,6H,Ar-H),7.32–7.28(m,2H,Ar-H),7.16(t,J=7.2H z,1H,Ar-H),7.10(t,J=7.2Hz,1H,Ar-H),7.07(s,1H,Ar-H),5.52(dd,J=1.8,11.4Hz,1H,H-1),5.05(d,J=10.8Hz,1H,-CH2Ph),4.77(d,J=11 .4Hz,1H,-CH2Ph),4.67(d,J=12.0Hz,1H,-CH2Ph),4.65(d,J=12.0Hz,1H,-CH2Ph),4.09(s,1H),3.93(t,J=9.0Hz,1H),3.81(m,1H,H-5),3.7 8(dd,1H,J=5.4,9.0Hz,H-6a),3.63(dd,1H,J=5.4,8.4Hz,H-6b),2.82(q,J=12Hz,H-2a),2.28(s,3H),2.19(m,1H,H-2b),1.04(m,21H,TIPS). 13 C NMR (151MHz, CDCl3) δ139.24,138.19,136.05,129.46,128.51,128.17,127.74,127.37,127.32,122.12,121.78,119 .51,118.99,111.84,110.17,81.91,78.01,77.71,74.49,71.61,70.31,61.68,31.95,18.01,11.88,9.62.HRMS(ESI + ):calc.for C38 H 51 NNaO4Si + [M+Na] + 636.3480, found: 636.3465.

[0245] Example 99: Trivalent iodine reagent participates in glycosylation to prepare compound III-47

[0246]

[0247] According to the standard operating procedure, donor I-26 (31.1 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. After CuCl was added and I-26 was completely converted, acceptor II-39 (8.8 μL, 0.043 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was completed, the white solid compound III-47 (23.7 mg, 84%) was obtained. 1 H NMR(600MHz, CDCl3) δ7.95(d,J=7.2Hz,2H,Ar-H),7.86(d,J=7.2Hz,2H,Ar-H),7.54(t,J=7.2Hz,2H,Ar-H),7.43–7.38(m,4H,Ar-H),7.36–7.23 (m,15H,Ar-H),4.96(d,J=10.8Hz,1H,-CH2Ph),4.94–4.90(m,1H,H-1),4.89(d,J=10.8Hz,1H,-CH2Ph),4.84(d,J=10.8Hz,1H,-CH2Ph),4.71(d, J=11.4Hz,1H,-CH2Ph),4.66(d,J=11.4Hz,1H,-CH2Ph),4.61(d,J=10.8Hz,1H,-CH2Ph),4.47(dd,J=12.0,2.4Hz,1H),4.42(dd,J=12.0,4.8Hz,1 H),3.95(ddd,J=9.0,4.8,2.4Hz,1H,H-5),3.90–3.85(m,2H),3.61(t,J=8.4Hz,1H),3.43(dd,J=15.6,4.8Hz,1H),3.31(dd,J=15.6,8.4Hz,1H). 13CNMR (150MHz, CDCl3) δ197.5,166.4,138.4,137.9,137.8,137.1,133.3,133.1,130.0,129.8,128.8,128.7,128.6,128. 6,128.4,128.3,128.2,128.2,128.1,128.0,128.0,82.1,79.6,77.9,75.6,75.2,73.6,71.2,71.1,64.0,35.8.HRMS(ESI + ):calc.for C 42 H 40 NaO7[M+Na] + 679.2666, found: 679.2666.

[0248] Example 100: Trivalent iodine reagent participates in glycosylation to prepare compound III-48

[0249]

[0250] According to the standard operating procedure, donor I-02 (20 mg, 0.060 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (30.0 mg, 0.09 mmol, 1.3 equivalent) and molecular sieve were added to the reaction flask. CuCl was added and after I-02 was completely converted, acceptor II-40 (13.7 mg, 0.120 mmol, 2.0 equivalent) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-48 (15.2 mg, 81%) was obtained. 1 H NMR (600MHz, CDCl3) δ8.69(s,1H,NH),7.93–7.81(m,3H),7.63–7.49(m,4H),6.46(d,J=9.6Hz,1H),5.45(t,J=3.6Hz,1H),5.30(dd,J=9.6,3.6Hz,1H) ,4.86(dd,J=3.6,1.2Hz,1H),4.32(q,J=7.2Hz,1H,H-5),2.21(s,3H,-COCH3),2.19(s,3H,-COCH3),1.96(s,3H,-COCH3),1.58(d,J=7.2Hz,3H,-CH3).

[0251] Example 101: Trivalent iodine reagent participates in the glycosylation preparation of compound III-49

[0252]

[0253] According to the standard operating procedure, donor I-17 (80 mg, 0.153 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (76.7 mg, 0.230 mol, 1.5 equivalent) and molecular sieve were added to the reaction flask. After CuCl was added and I-17 was completely converted, acceptor II-41 (31.7 mg, 0.230 mmol, 1.5 equivalent) and TfOH were added. After the reaction was completed, the colorless syrupy compound III-49 (62.3 mg, 68%) was obtained. 1 H NMR (400MHz, CDCl3) δ7.96 (d, J=8.4Hz, 4H, Ar-H), 7.65–7.07 (m, 15H, Ar-H), 5.85 (t, J=10.0Hz, 1H, H-2), 5.30 (dd, J=10.0, 3.2Hz, 1H, H-3), 4.86 (d, J=10.0Hz,1H,H-1),4.58(s,2H,2×-CH2Ph),4.41(s,1H,H-4),3.88–3.78( m,3H),2.73(s,1H,OH),2.68-2.57(m,2H),0.98(t,J=7.6Hz,3H).HRMS(ESI + ):calc.for C 35 H 34 NaO7S[M+Na] + 621.1917, found: 621.1912.

[0254] Example 102: Trivalent iodine reagent participates in glycosylation to prepare compound III-50

[0255]

[0256] Compound S5 (170 mg, 0.76 mmol) was dissolved in DCM and placed in water at 0 °C. Then, di-tert-butyltrifluoromethanesulfonate (0.25 mL, 0.76 mmol) was added, and the mixture was stirred in water at 0 °C for 30 min. Next, pyridine (0.19 mL, 2.28 mmol) was added, and the mixture was stirred for 15 min. After the reaction was complete, the mixture was extracted with ethyl acetate and washed successively with water and saturated NaCl. The organic phase was dried over anhydrous Na₂SO₄ and concentrated under vacuum, followed by silica gel column chromatography to obtain a white solid S6 (254 mg, 72%). 1H NMR (600MHz, CDCl3) δ4.44(d,J=3.6Hz,1H),4.31(d,J=9.6Hz,1H,H-1),4.27(d,J=1.8Hz,2H,H-6 ),3.68(t,J=9.6Hz,1H,H-2),3.52(m,1H,H-5),3.47(d,J=1.2Hz,1H),2.81–2.72(m,3H),2.58(br s,1H,OH),1.63(br s,1H,OH),1.31(t,J=7.4Hz,3H,CH3),1.06(s,9H),1.05(s,9H). 13 C NMR (150MHz, CDCl3) δ86.37,75.59,75.18,72.81,70.78,67.23,27.70,27.50,24.85,23.47,20.77,15.29.HRMS (ESI + ):calc.for C 16 H 32 NaO5SSi[M+Na] + 387.1632, found: 387.1642.

[0257] Compound S6 was dissolved in DMF and placed in water at 0°C. Then, NaH (104 mg, 2.6 mmol) and BnBr (0.78 mL, 6.5 mmol) were added sequentially. The mixture was then brought to room temperature. After the reaction of the starting material was complete, the reaction was terminated with methanol and extracted with ethyl acetate. The mixture was washed successively with water and saturated NaCl. The organic phase was dried over anhydrous Na2SO4 and concentrated under vacuum. The solution was then purified by silica gel column chromatography to obtain a white solid I-29 (268 mg, 90%). 1H NMR (600MHz, CDCl3) δ7.41(t,J=7.2Hz,4H,Ar-H),7.33(m,4H,Ar-H),7.29(m,2H,Ar-H),4.85(s,2H),4.77(d ,J=12.0Hz,1H,PhCH2),4.69(d,J=12.0Hz,1H,PHCH2),4.50(d,J=2.4Hz,1H,H-4),4.40(d,J=9.6Hz,1H,H-1), 4.24 (dd, J=1.2, 12.6Hz, 1H, H-6a), 4.19 (dd, J=1.8, 12.6Hz, H-6b), 3.76 (t, J=9.6Hz, 1H, H-2), 3.45 (dd, J=3. 0,9.6Hz,1H,H-3),3.29(s,1H,H-5),2.70(m,2H,SCH2),1.29(t,J=7.8Hz,3H,CH3),1.10(s,9H),1.07(s,9H). 13 C NMR (150MHz, CDCl3) δ138.60,138.57,128.60,128.57,128.44,127.96,127.84,85.43,82.94, 77.65,75.96,75.17,71.12,70.20,67.60,27.79,27.76,25.41,23.56,20.82,15.27.HRMS(ESI + ):calc.for C 30 H 44 NaO5SSi[M+Na] + 567.2571, found: 567.2569

[0258]

[0259] According to the standard operating procedure, donor I-29 (28.1 mg, 0.052 mmol, 1.2 equivalents), trivalent iodine reagent IV-1 (21.6 mg, 0.065 mmol, 1.5 equivalents) and molecular sieve were added to the reaction flask. CuCl was added and after I-29 was completely converted, acceptor II-42 (11.9 mg, 0.043 mmol, 1.0 equivalents) and TfOH·DTBP were added. After the reaction was complete, the colorless syrupy compound III-50 (30.7 mg, 94%) was obtained. 1H NMR (600MHz, CDCl3) δ7.42–7.38(m,4H,Ar-H),7.33(m,4H,Ar-H),7.28(m,2H,Ar-H),5.52(d,J=4.8Hz,1H),5.45(d,J=5.4Hz,1H),4.78(d,J= 12.0Hz,1H,PhCH2),4.72(d,J=12.6Hz,3H),4.59(dd,J=2.4,7.8Hz,1H),4.48(d,J=3.0Hz,1H),4.30(dd,J=2.4,5.4Hz,1H),4.26(dd,J=1.8,7 .8Hz,1H),4.25–4.22(m,1H),4.21(dd,J=1.8,10.2Hz,1H),4.08(dd,J=1.2,12.0Hz,1H),4.00(m,1H),3.97(s,1H),3.63(dd,J=2.4,9.6Hz,1 H),2.82(dd,J=7.8,13.2Hz,1H),2.73(dd,J=6.6,13.2Hz,1H),1.52(s,3H),1.44(s,3H),1.33(s,3H),1.32(s,3H),1.04(s,9H),0.95(s,9H). 13 C NMR (150MHz, CDCl3) δ139.02,138.34,128.45,128.44,128.29,127.76,127.70,127.59,109.49,108.89,96.88,85.66,78.23,73.72,72 .68,71.64,71.27,71.25,71.16,70.69,68.18,67.22,66.53,30.64,27.76,27.40,26.29,26.15,25.09,24.74,23.55,20.81.HRMS(ESI + ):calc.for C 40 H 58 NaO 10 SSi[M+Na]+781.3412,found:781.3398.

[0260] Example 103: Trivalent iodine reagent participates in glycosylation to prepare compound III-51

[0261]

[0262] S7 (197 mg, 0.79 mmol, 1.0 equivalent) was weighed into a reaction flask, degassed with argon, dissolved in acetonitrile, and placed in water at 0 °C. NaH (48 mg, 1.19 mmol, 1.5 equivalent) was slowly added to the reaction flask, and the mixture was stirred for 10 min. Then MeI (169 mg, 1.19 mmol, 1.5 equivalent) was added, and the mixture was slowly brought to room temperature. After the reaction was complete, the reaction was terminated with methanol. The solvent was evaporated, diluted with EA, washed twice with H2O, and then washed once with saturated NaCl solution. The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain a syrupy liquid S8 (221.4 mg, 97%). 1 H NMR (400MHz, CDCl3) δ4.42(1H,d,J=1.6Hz,H-1),4.22(1H,t,J=5.6Hz,H-3),3.92(1H,dd,J=2.8,5.6Hz,H-4),3.71(1H,dq,J=2.8,6.8,Hz,H- 5),3.51(3H,s,-OMe),3.33(1H,dd,J=1.6,5.2Hz,H-2),2.05(2H,m,-SCH2),1.56(3H,s,-CH3),1.40(3H,d,J=6.8,-CH3),1.34(3H,s,-CH3). 13 C NMR (100MHz, CDCl3) δ110.05,83.77,77.09,74.53,73.70,72.70,61.94,26.07,25.60,16.94,15.26.HRMS (ESI + ):calc.forC 12 H 22 NaO4S[M+Na] + 285.1131, found: 285.1127.

[0263] Take S8 (170 mg, 0.65 mmol) and place it in a reaction flask. Add (AcOH:H2O = 4:1) to dissolve it. Place the flask at 65 °C and monitor the reaction with TLC. After the reaction is complete, evaporate the solvent and add MoO2(acac)2 (4.2 mg, 0.013 mmol, 0.02 equivalents). Then add 1,4-dioxane to dissolve it. Place the flask in an ice bath and add 2,4,6-trimethylpyridine (157 mg, 1.3 mmol, 2.0 equivalents). Stir for 10 min and then add AcCl (152.6 mg, 1.94 mmol, 1.5 equivalents). Slowly raise the temperature to room temperature. The reaction was monitored by TLC. After the reaction was complete, the reaction was terminated with ice water. The solvent was evaporated, diluted with EA, washed twice with H2O, once with HCl (1M), once with saturated NaHCO3, and once with saturated NaCl solution. The solution was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain a colorless syrupy liquid S9 (157.6 mg, 92%). 1 H NMR (400MHz, CDCl3) δ4.74(1H,t,J=3.2Hz,H-3),4.52(1H,d,J=0.4Hz,H-1),3.65(1H,m,H-2),3.62(1H,m,H-4),3.56(3H,s,-OMe), 3.49(1H,dq,J=0.8,6.4,Hz,H-5),3.42(1H,d,J=11.2Hz,-OH),2.70(2H,m,-SCH2),2.13(3H,s,-OAc),1.25(6H,m,-CH3,-SCH2CH3). 13 C NMR (100MHz, CDCl3) δ170.55,84.47,80.52,76.34,73.18,70.30,62.44,25.79,21.21,16.92,15.23.HRMS (ESI + ):calc.for C 11 H 20 NaO5S[M+Na] + 287.0924 found: 287.0927.

[0264] S9 (313 mg, 1.18 mmol, 1.0 equivalent) was placed in a reaction flask, dissolved in DCM, and pyridine (375 mg, 4.74 mmol, 4.0 equivalent) was added. The mixture was placed at 0 °C, and then TESOTf (626 mg, 2.37 mmol, 2.0 equivalent) was added. The reaction was monitored by TLC until complete. The solvent was evaporated, and the reaction was terminated with saturated NaHCO3. The mixture was diluted with DCM, washed once with saturated copper sulfate, once with H2O, and once with saturated NaCl solution. The mixture was dried over anhydrous sodium sulfate, concentrated, and purified by silica gel column chromatography to obtain a yellow syrup liquid I-36 (430.5 mg, 96%). 1 H NMR (600MHz, CDCl3) δ4.78(1H,t,J=3.6Hz,H-3),4.54(1H,d,J=1.2Hz,H-1),3.73(1H,m,H-2or H-4),3.57(1H,m,H-2or H-4),3.51(1H,dq,J=0.6,6.0,Hz,H-5),3.47(3H,s,-OMe),2.69(2H,m,-SCH2),2.16(3H ,s,-OAc),1.28(6H,m,-CH3,-SCH2CH3),0.97(9H,t,J=7.8Hz,-TES),0.64(6H,q,-TES). 13 C NMR (100MHz, CDCl3) δ170.52,85.07,78.54,76.23,74.45,69.91,61.75,29.84,25.65,21.35,17.41,15.16,7.08,5.22.HRMS(ESI + ):calc.for C 17 H 34 NaO5SSi[M+Na] + 401.1788 found: 401.1790.

[0265]

[0266] Donor I-36 (15 mg, 0.040 mmol, 1.0 equivalent), trivalent iodine reagent IV-1 (19.9 mg, 0.069 mmol, 1.5 equivalent) and molecular sieve were added to a reaction flask. CuCl was added and after I-36 was completely converted, acceptor II-19 (8.8 mg, 0.044 mmol, 1.1 equivalent) was added. After the reaction was complete, the colorless syrupy compound III-51 (18.1 mg, 87%) was obtained. 1H NMR (600MHz, CDCl3) δ7.87(d,J=8.4Hz,1H),7.51(d,J=7.8Hz,1H),7.43(t,J=7.8Hz,1H),7.30(t,J=7.8Hz 1H),6.49(s,1H),5.13(t,J=3.0Hz,1H),4.22(q,J=6.6Hz,1H),3.85(s,1H),3.56(s,1H),3.51(s,3H),2.44(m,2 H),2.15(s,3H),1.62-1.57(m,2H),1.50-1.44(m,2H),1.26(d,J=6.6Hz,3H),0.93(t,J=7.2Hz,3H),0.15(s,9H).

[0267] Those skilled in the art will readily understand that the above description is merely a preferred embodiment of the present invention and is not intended to limit the present invention. Any modifications, equivalent substitutions, and improvements 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 glycosylation method involving trivalent iodine reagent, characterized in that, The glycosylation method is as follows: a glycosyl donor (I) is activated in the presence of a trivalent iodine reagent and a transition metal catalyst, and then reacts with an acceptor (II) under acid catalysis to obtain a glycosylated product (III); the amount of the transition metal catalyst is 0.01% to 10% of the acceptor (II); the trivalent iodine reagent is selected from the iodine ylide reagent of formula (IV-a) or the iminoiodide of formula (IV-b); The formula (IV-a) is selected from compounds with any of the following structures: ； The structure of formula (IV-b) is as follows: ； The reaction formula is as follows: The glycosyl donor (I) is selected from compounds with any of the following structures: 、 ； The receptor (II) is selected from compounds with any of the following structures: The carbohydrate acceptor containing one or more free hydroxyl groups is selected from compounds with any of the following structures: ； Alcohol or phenolic acceptors are selected from compounds with any of the following structures: ； Flavonoid receptors are selected from compounds with the following structures: ； Carboxylic acid or phosphate acceptors are selected from compounds with the following structures: ； Pyrimidine receptors are selected from compounds with any of the following structures: ； Purine receptors are selected from compounds with any of the following structures: ； Amide receptors are selected from compounds with any of the following structures: ； Sulfonamide receptors are selected from compounds with the following structures: ； Guanidine receptors are selected from compounds with the following structures: ； Arylamine receptors are selected from compounds with the following structures: ； Indole receptors are selected from compounds with the following structures: ； Enol silyl ether receptors are selected from compounds with any of the following structures: Thiol or thiophenol acceptors are selected from compounds with any of the following structures: ； The transition metal catalyst is cuprous chloride, cuprous bromide, cuprous iodide, cuprous bromide dimethyl sulfide, cuprous tetrafluoroborate tetraacetonitrile, cuprous trifluoromethanesulfonate, [1,3-bis(2,6-diisopropylphenyl)imidazol-2-yl]cuprous chloride, cuprous diphenyl phosphate, cuprous thiophene-2-carboxylate, cuprous chloride, cuprous bromide, copper acetate, copper acetylacetonate, copper hexafluoroacetylacetonate, copper p-toluenesulfonate, copper trifluoromethanesulfonate, copper trifluoromethanesulfonate toluene complex, rhodium(II) acetate dimer, or rhodium(II) octoate dimer. The acid catalyst is trifluoromethanesulfonic acid, 2,5-di-tert-butylpyridinium trifluoromethanesulfonic acid, 2,5-di-tert-butyl-4-methylpyridinium trifluoromethanesulfonic acid, bis(trifluoromethanesulfonyl)imide; boron trifluoride ether, trimethylsilyl trifluoromethanesulfonic acid, triethylsilyl trifluoromethanesulfonic acid, or triphenylmethyltetra(pentafluorophenyl)borate. Alternatively, the glycosylation method may be as follows: a glycosyl donor (I) is activated in the presence of a trivalent iodine reagent and a transition metal catalyst, and then reacts with an acceptor (II) to obtain a glycosylated product (III); the amount of the transition metal catalyst is 0.01% to 10% of the acceptor (II); the definitions of the glycosyl donor (I), the transition metal catalyst, and the trivalent iodine reagent are as defined in Scheme 1. The receptor (II) is a carboxylic acid receptor with the following structural formula: .

2. The glycosylation method according to claim 1, characterized in that, The molar ratio of the receptor (II) to the glycosyl donor (I) is 1:(0.5~2). The molar ratio of the receptor (II) to the trivalent iodine reagent is 1:(1~6).

3. The glycosylation method according to claim 1 or 2, characterized in that, In Scheme 1, the amount of acid catalyst is 5-30% of the acceptor (II).

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