Tert-butyl ethynyl thiophenol ether glycosyl donor, preparation method thereof and application of tert-butyl ethynyl thiophenol ether glycosyl donor in nucleoside synthesis

Abstract

The invention discloses a tert-butyl ethynyl thiophenol ether glycosyl donor, a preparation method of the tert-butyl ethynyl thiophenol ether glycosyl donor and application of the tert-butyl ethynyl thiophenol ether glycosyl donor in nucleoside synthesis. The structure of the donor is as follows: # imgabs0 # Gly is any one of the following structures: # imgabs1 # imgabs2 # PG is one or more hydroxyl protecting groups, glycosyl or carbohydrate chains. The novel glycosyl donor which is simple to prepare and good in stability is prepared, and the method for constructing the C-N glucosidic bond of nucleoside, which is simple to operate, mild in condition, high in reaction stereoselectivity and regioselectivity and environment-friendly, is used for constructing the C-N glucosidic bond of nucleoside by utilizing the glycosyl donor.

Description

Technical Field

[0001] The invention belongs to the technical field of organic synthesis, and particularly relates to a tert-butylethynylthiophenol ether sugar donor, a preparation method thereof and application thereof in nucleoside synthesis. Background Art

[0002] Glycosylation reaction usually refers to the process of adding a leaving group to the anomeric position of a sugar to obtain a glycosyl donor, which then forms a glycosidic bond with a nucleophile (usually a substrate with exposed hydroxyl, amino or thiol groups, called a glycosyl acceptor) to obtain a glycosylated product. The efficient construction of glycosidic bonds is a core problem in the field of sugar synthesis, and the development of new glycosyl donors is one of the effective ways to solve this problem.

[0003] At present, the more classic glycosyl donors include brominated glycosides, trichloroacetimidate donors (Schmidt donors), o-alkynylbenzoate donors (Yu donors), glucosinolates, etc. Among them, the glycosylation method using brominated glycosides as donors (Koenigs-Knorr method) is the earliest developed glycosylation method. The donor has the advantages of simple preparation and high reaction efficiency, but the donor needs to be activated under the conditions of equivalent toxic mercury salts or silver salts, the reaction conditions are harsh and the environment is polluted; at the same time, brominated glycosides are unstable and not conducive to storage, and generally need to be prepared and used immediately, and the operation is relatively cumbersome. The Schmidt donor glycosylation method (trichloroacetimidate method) is a glycosylation method developed by Professor RR Schmidt of Germany in 1980. It is the first glycosylation method that only requires a catalytic amount of a promoter: a proton acid (TfOH) or a Lewis acid (TMSOTf, BF3·Et2O) as a catalyst. This method has high donor activity and relatively mild reaction conditions. It has been widely used in the synthesis of sugar compounds. However, due to the poor stability of the Schmidt donor, it is difficult to prepare, purify and characterize the highly active sugar donor. At the same time, the leaving group of the Schmidt donor after activation is trichloroacetamide, which has a relatively strong nucleophilicity and will interfere with the normal glycosylation process through receptor competition, thus limiting its scope of use to a certain extent. The glycosylation method using glucosinolate as donor has the advantages of simple donor preparation, high reaction activity, and the leaving group can be orthogonal to a variety of protecting groups, which can facilitate the efficient acquisition of glycoside building blocks. However, the odor is not very friendly during the preparation of the glucosinolate donor, and the leaving group has a strong nucleophilicity after leaving, which will interfere with the normal glycosylation process. At the same time, the reaction conditions require an equivalent amount of thiophilic reagent and are highly acidic, which is not suitable for the construction of glycosidic bonds of some acid-sensitive substrates. The glycosylation method using o-alkynylbenzoate as donor was developed by the research group of Academician Yu Biao of Shanghai Institute of Organic Chemistry. The donor is activated under the condition of catalytic amount of PPh3AuNTf2 or PPh3AuOTf as catalyst. The reaction conditions are very mild and can be applied to the construction of glycosidic bonds of acid-sensitive substrates. This method has been successfully applied to the synthesis of many complex carbohydrate compounds. However, the disadvantage of this method is that after the leaving group is installed at the anomeric position, it is impossible to perform protective group operation with ester protective groups, and the price of monovalent gold as a catalyst is expensive, and the reaction needs to be carried out under the condition of more than 0.1 equivalent of catalyst. Later, with the efforts of sugar chemists, a variety of new glycosylation methods were reported one after another, but there are deficiencies such as insufficient mild reaction conditions, poor reaction activity, and poor orthogonality with other protective groups. Therefore, it is necessary to develop a new glycosylation method, the promoter system required for the reaction is mild, the substrate is universal, the leaving group does not interfere with the reaction, the donor is stable and can be orthogonally operated with a variety of protective groups.

[0004] At present, there are two main methods for synthesizing nucleosides in vitro: enzymatic synthesis and chemical synthesis. The glycosyltransferases and glycosidases required for enzymatic synthesis are few in variety, expensive, and have poor universality, so their application is greatly limited. Chemical synthesis can obtain accurate structures, so it is the mainstream direction of current research. The chemical synthesis method of nucleoside compounds mainly forms a CN glycosidic bond between a glycosyl donor and a base acceptor by chemical methods. The construction of the CN glycosidic bond between sugar and base has always been the focus and difficulty of sugar chemistry research. At present, nucleoside drugs are an important class of drugs used clinically to treat viral infectious diseases, tumors, and AIDS. This type of drug has saved the lives of countless people infected with bacteria and fungi in the past few decades, and has played a vital role in prolonging human life. In the chemical synthesis of this type of drug molecule, the construction of the nucleoside bond is a key step. However, this type of glycosidic bond is not particularly easy to construct, mainly for the following reasons:

[0005] 1) The solubility of the base as the acceptor in this glycosylation is extremely poor, and it cannot be completely dissolved even in DMSO, which makes this type of glycosylation reaction difficult to carry out; 2) In pyrimidine bases, both oxygen atoms and nitrogen atoms have affinity, so two glycosylation products, CO and CN, may be obtained during the glycosylation reaction. For purine bases, there are regional selectivity issues between N7 and N9. These problems pose great challenges to the precise construction of base glycosidic bonds.

[0006] Based on the importance of the construction of nucleoside CN bonds in the research of new nucleoside and nucleotide drugs, it is very necessary to develop a method for constructing the CN glycosidic bond of nucleosides that is simple to operate, has mild conditions, high stereoselectivity and regioselectivity, and is environmentally friendly. Summary of the invention

[0007] The technical problem to be solved by the present invention is to provide a tert-butyl ethynyl thiophenol ether glycosyl donor, a preparation method thereof and application thereof in nucleoside synthesis. The operation of constructing the CN glycosidic bond of the nucleoside is simple, the conditions are mild, the stereoselectivity and regioselectivity of the reaction are high, and the reaction is environmentally friendly.

[0008] Based on the above purpose, the present invention adopts the following technical solutions:

[0009] A tert-butyl ethynyl thiophenol ether sugar donor, the structure of the donor is as follows: Gly is any of the following structures: PG is one or more hydroxyl protecting groups, glycosyl groups or sugar chains.

[0010] The above-mentioned tert-butylethynylthiophenol ether sugar donor is specifically a compound with the following structure:

[0011]

[0012] R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, Bn is benzyl, and X is Cl, Br or I.

[0013] The preparation method of the above-mentioned tert-butyl ethynyl thiophenol ether sugar donor, the synthesis route is as follows:

[0014]

[0015] R is R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, Bn is benzyl, and X is Cl, Br or I;

[0017] The specific preparation process is as follows: the compound shown in formula I and 3,3-dimethyl-1-butyne undergo Sonogashira reaction to obtain the compound shown in formula III.

[0018] Furthermore, the Sonogashira reaction includes the following steps: dissolving compound I, Ph3P, Pd(PPh3)2Cl2, and CuI in an organic solvent, cooling to -78°C to -40°C in an inert gas atmosphere, adding 3,3-dimethyl-1-butyne, heating to 50 to 100°C, and reacting until TLC shows that the reaction is complete, wherein the organic solvent is selected from one or more of N,N-dimethylformamide, diisopropanolamine, tetrahydrofuran, dichloromethane, toluene, and acetone.

[0019] Preferably, the molar ratio of the compound represented by formula I, 3,3-dimethyl-1-butyne, (PPh3)2PdCl2, CuI and PPh3 is 1:(2.5~3.5):(0.08~0.12):(0.3~0.5)(0.3~0.5).

[0020] Preferably, the organic solvent is a mixed solvent of N,N-dimethylformamide and diisopropanolamine, and the volume ratio of N,N-dimethylformamide to diisopropanolamine is 1:(1-3).

[0021] The application of the above-mentioned tert-butyl ethynyl thiophenol ether sugar donor in the synthesis of nucleosides, the synthesis route is as follows:

[0022]

[0023] R is R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, and Bn is benzyl; R3 is H, F or Cl, R4 is Cl, Br or I, R5 is H, F, I, CH3, CF3 or CH3CH2, and X is Cl, Br or I;

[0025] The specific synthesis process is as follows:

[0026] Method A: dissolving the donor represented by formula III and the acceptor represented by formula IV in an organic solvent, and obtaining the nucleoside compound represented by formula V in the presence of a desiccant and under the action of a catalyst;

[0027] Method B: dissolving the donor represented by formula III and the acceptor represented by formula IV in an organic solvent and obtaining the nucleoside compound represented by formula V under the action of a desiccant, a promoter and a catalyst;

[0028] The organic solvent is preferably one or more of dichloromethane, chloroform, carbon tetrachloride, 1,2-dichloroethane, DMF, toluene, benzene, dioxane, pyridine, glacial acetic acid, tetrahydrofuran, triethylamine, ethyl acetate, DMSO or diethyl ether. The catalyst is a monovalent gold complex, preferably PPh3AuNTf2 or PPh3AuOTf. The promoter is BSTFA, NIS or TMSOT, preferably BSTFA.

[0029] Method A also includes adding hexafluoroisopropanol into the organic solvent, the volume ratio of the organic solvent to the hexafluoroisopropanol is (3-5):1, and the concentration of the donor in the organic solvent and the hexafluoroisopropanol is 20-170 mM.

[0030] Preferably, in method A, the molar ratio of the donor shown in formula III and the acceptor shown in formula IV is (1.3-1.1):1, and the molar ratio of the donor shown in formula III and the catalyst is 1:(0.02-0.2); the concentration of the donor in the organic solvent is 30-60 mM.

[0031] In method B, the molar ratio of the donor represented by formula III, the acceptor represented by formula IV, the promoter and the catalyst is 1:(1-2):(4-8):(0.02-0.2); the concentration of the donor in the organic solvent is 20-100 mM.

[0032] Preferably, the desiccant is a molecular sieve, and the amount of the molecular sieve added is 0.3 to 0.8 g / mmol based on the receptor, preferably Molecular sieve or acid-washed molecular sieve, more preferably Molecular sieve.

[0033] The invention prepares a novel glycosyl donor with simple preparation and good stability, and uses the glycosyl donor to provide an environmentally friendly method for constructing CN glycosidic bonds of nucleosides with simple operation, mild conditions, high stereoselectivity and regioselectivity of the reaction. DETAILED DESCRIPTION

[0034] Part I: Synthesis of the Donor

[0035] Example 1

[0036]

[0037] β-Pentaacetylglucose S1 (2.0 g, 5.12 mmol) was dissolved in dry dichloromethane (20 mL), 2-bromobenzenethiol (1.1 mL, 9.2 mmol) and BF3-Et2O (1.8 mL, 14.6 mmol) were added under ice bath, the mixture was warmed to room temperature, stirred until the substrate reaction was complete as detected by TLC, triethylamine was added to quench the reaction, DCM was added to dilute, saturated NaHCO3 was added to wash, dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to obtain the crude product of S2, which was purified by silica gel column chromatography (petroleum ether / ethyl acetate = 3:1) to obtain S2 (2.40 g, 90%), and directly proceeded to the next step.

[0038] (PPh3)2PdCl2 (125 mg, 0.19 mmol), CuI (145 mg, 0.76 mmol), PPh3 (202 mg, 0.77 mmol) and S2 (1.0 g, 1.93 mmol) were added to a mixed solvent of DMF / DIPA (24 mL, v / v = 1:2), evacuated and filled with nitrogen, 3,3-dimethyl-1-butyne (0.7 mL, 5.7 mmol) was added at -78 °C, sealed, stirred and reacted at 80 °C for 8 h, then cooled to room temperature, quenched with saturated NH4Cl solution, desalted through a short silica gel column, diluted with ethyl acetate, washed with water and saturated brine in turn, filtered and concentrated by rotary evaporation to obtain the crude product of 1a, which was purified by silica gel column (petroleum ether / ethyl acetate = 3:1) to obtain donor 1a (962 mg, 96%) as a light yellow foamy solid, [α] D 25 = -86.4 (c 0.5, CHCl3); 1H NMR (400MHz, CDCl3) δ7.44 (dd, J=7.8, 1.3Hz, 1H), 7.35 (dd, J=7.5, 1.6Hz, 1H), 7.21 (td, J=7.6, 1.7Hz,1H),7.15(td,J=7.5,1.4Hz,1H),5.27(t,J=9.3Hz,1H),5.20-5.13(m,1H),5.11(t,J=8.7 Hz,1H),4.95(d,J=10.1Hz,1H),4.24(dd,J=12.3,5.7Hz,1H),4.14(dd,J=12.4,2.3Hz,1H),3.80 (ddd,J=10.0,5.8,2.4Hz,1H),2.06(s,3H),2.04(s,3H),2.03(s,3H),2.01(s,3H),1.32(s,9H); 13 C NMR (100MHz, CDCl3) δ170.7,170.3,169.5,169.25,136.4,132.4,128.9,128.2,126.7,1 24.8,105.7,84.55,75.9,74.1,70.1,68.6,62.5,31.0,28.4,20.8,20.7.HRMS(ESI)m / z calcd for C 26 H 32 O9SNa[M+Na] + :543.1659;

[0039] found:543.1667.

[0040] Example 2

[0041]

[0042] S3 (1.0 g, 1.3 mmol) was used to replace S2 in Example 1 to obtain donor 1b (0.98 g, 98%) as a white foamy solid. [α] D 25 = +4.4 (c 0.5, CHCl3); 1H NMR (400MHz, CDCl3) δ8.08-7.98(m,2H),7.94-7.91(m,4H),7.82-7.80(m,2H) ,7.58-7.23(m,14H),7.05(td,J=7.6,1.1Hz,1H),6.90(td,J=7.7,1.5Hz,1H), 6.00(t,J=9.5Hz,1H),5.73-5.64(m,2H),5.29(d,J=10.0Hz,1H),4.68(dd,J=1 2.2, 2.6Hz, 1H), 4.49 (dd, J = 12.2, 6.9Hz, 1H), 4.33-4.28 (m, 1H), 1.10 (s, 9H); 13 CNMR (100MHz, CDCl3) δ166.2,165.9,165.4,165.15,136.9,133.7,133.4,133.3,132.1,130.05,130.0,129.9,129.8,129.65,129.1,128 .8,128.75,128.6,128.55,128.5,128.4,128.1,126.4,124.5,105.7,84.9,76.6,76.4,74.2,70.6,69.8,63.7,30.7,28.2; HRMS(ESI)m / z calcd for C 46 H 44 O9SN[M+NH4] + :786.2731; found:786.2732.

[0043] Example 3

[0044]

[0045] S4 (1.0 g, 2.4 mmol), NaHCO3 (4.0 g, 48 mmol) and acetone (3.5 mL, 48 mmol) were added to H2O (12 mL), and Oxone (38 mL, 0.4 mol / L) was added dropwise at 0°C. The mixture was stirred until the substrate reaction was complete as detected by TLC. Cold CH2Cl2 was added to the reaction solution, and the mixture was washed with ice water and saturated brine in turn, dried over anhydrous Na2SO4, filtered and concentrated by rotary evaporation to obtain the crude intermediate, which was directly transferred to the next step without purification.

[0046] The crude intermediate (1.04 g, 2.4 mmol) was added to dry CH2Cl2 (10 mL), and 2-bromobenzenethiol (0.6 mL, 4.8 mmol) and K2CO3 (663 mg, 4.8 mmol) were added at room temperature. The mixture was stirred until the substrate reaction was complete as detected by TLC. CH2Cl2 was added to dilute the mixture, and the mixture was washed with water and saturated brine in turn, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / ethyl acetate = 4:1) to give S5 (1.2 g, two-step yield 78%) as a white solid.

[0047] S5 (1.0 g, 1.6 mmol) was dissolved in dry pyridine (10 mL), BzCl (0.28 mL, 2.4 mmol) was added at 0°C, the temperature was warmed to room temperature, and the mixture was stirred until the substrate reaction was complete as detected by TLC. After dilution with EtOAc, the mixture was washed with 2M HCl and saturated brine in sequence, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / ethyl acetate = 4:1) to obtain white solid S6 (1.1 g, 93%).

[0048] S6 (0.5 g, 0.7 mmol) was used to replace S2 in Example 1 to obtain donor 1c (0.5 g, 93%) as a white foamy solid. D 25 = +14.9 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.01-7.98(m,2H),7.57-7.52(m,2H),7.42-7.38(m,2H),7.34-7.2 6(m,9H),7.23-7.21(m,2H),7.14-7.11(m,5H),7.07-7.05(m,2H),5.45(dd,J=10.1,9.0 Hz,1H),5.00(d,J=10.1Hz,1H),4.84(d,J=10.9Hz,1H),4.75(d,J=11.0Hz,1H),4.68(d, J=11.0Hz,1H),4.65-4.51(m,3H),3.90(t,J=8.8Hz,1H),3.86-3.68(m,4H),1.09(s,9H). 13C NMR (100MHz, CDCl3) δ165.2,138.3,138.05,138.0,137.8,133.2,131.9,130.1,129.9,128.6,128.5,128.4(2C),128.2,128.1 ,128.0,127.9,127.8,127.7,125.95,124.0,105.4,84.7,84.5,79.6,75.5,75.3,73.65,72.5,69.2,30.7,28.2; HRMS(ESI)m / z calcd for C 46 H 50 O6SN[M+NH4] + :744.3353; found:744.3343.

[0049] Example 4

[0050]

[0051] 2-Bromobenzenethiol (0.2 mL, 1.68 mmol) was dissolved in dry acetone, K2CO3 (240 mg, 1.74 mmol) was added at 40°C, and S7 (0.93 g, 1.4 mmol dissolved in toluene) was added after stirring for 0.5 h. The reaction was continued until the substrate reaction was complete as detected by TLC. CH2Cl2 was added to dilute the mixture, and the mixture was washed with water and saturated brine in turn. The mixture was dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / ethyl acetate = 4:1) to obtain S8 (0.95 g, 88%) as a white foamy solid.

[0052] S8 (0.5 g, 0.65 mmol) was used to replace S2 in Example 1 to obtain donor 1d (0.48 g, 97%) as a white foamy solid. D 25 = +114.7 (c 0.5, CHCl3); 1H NMR (400MHz, CDCl3) δ8.11-8.09(m,2H),8.05-8.03(m,2H),7.94-7.92(m,2H),7.79-7.76(m,2H),7.66-7 .57(m,3H),7.52-7.40(m,6H),7.36-7.30(m,3H),7.26-7.22(m,2H),7.11-7.08(m,1H),6.97(td,J=7.7,1 .5Hz,1H),6.07(d,J=3.4Hz,1H),5.97(t,J=10.0Hz,1H),5.70(dd,J=9.9,3.4Hz,1H),5.29(d,J=10.1Hz, 1H), 4.62 (dd, J=11.5, 7.7Hz, 1H), 4.54 (dd, J=11.5, 4.9Hz, 1H), 4.48 (dd, J=7.8, 5.0Hz, 1H), 1.10 (s, 9H); 13 C NMR (100MHz, CDCl3) δ166.2,165.7,165.6,165.3,136.9,133.8,133.5,133.45,133.4,132.15,130.2,130.0,130.0,129.9,129.6, 129.3,129.0,128.8(2C),128.6,128.4,128.1,126.4,124.6,105.6,85.3,75.4,72.9,68.6,68.0,63.0,30.7,28.2; HRMS(ESI)m / z calcd for C 46 H 44 O9SN[M+NH4] + :786.2731; found:786.2718.

[0053] Example 5

[0054]

[0055] Referring to the synthesis process of S2 in Example 1, S9 (2.0 g, 5.1 mmol) was used instead of S1 to obtain S10 (2.5 g, 93%) as a white solid, which was directly transferred to the next step.

[0056] S10 (1.0 g, 1.9 mmol) was dissolved in CH3OH (10 mL), and NaOMe (freshly prepared) was added. The mixture was stirred until the substrate reaction was complete as detected by TLC. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column (CH2Cl2 / MeOH=10:1) to obtain the tetraol intermediate (0.63 g, 93%) as a white solid. The product was directly processed into the next step without further treatment.

[0057] The above intermediate (0.5 g, 1.4 mmol) was dissolved in dry pyridine (5 mL), BzCl (0.8 mL, 7 mmol) was added at 0°C, the temperature was warmed to room temperature, and the mixture was stirred until the substrate reaction was complete as detected by TLC. After dilution with EtOAc, the mixture was washed with 1 M HCl and saturated brine in sequence, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / ethyl acetate = 4:1) to obtain white foamy solid S11 (0.8 g, 73%).

[0058] S11 (100 mg, 0.13 mmol) was used to replace S2 in Example 1 to obtain donor 1e (90 mg, 93%) as a white foamy solid. D 25 = +48.8 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.09-8.06(m,2H),8.01-7.97(m,4H),7.86-7.84(dd,J=8.1,1.5Hz,2H),7. 63-7.50(m,4H),7.47-7.36(m,8H),7.30-7.26(m,2H),7.17(td,J=7.6,1.4Hz,1H),7.10(td,J=7. 7,1.6Hz,1H),6.13(t,J=10.1Hz,1H),6.03(dd,J=3.2,1.6Hz,1H),5.99-5.94(m,2H),5.06(ddd, J=10.3,5.2,2.4Hz,1H),4.59(dd,J=12.2,2.4Hz,1H),4.50(dd,J=12.2,5.2Hz,1H),1.38(s,9H). 13 CNMR(150MHz, CDCl3)δ166.3,165.6(2C),165.3,134.2,133.7,133.4,133.15,133.0,132.0,130.0(2C),129.9,129.9,129.4, 129.1,129.0,128.8,128.6,128.5,128.4,127.7,126.9,105.1,84.7,71.8,70.7,70.0,67.3,63.15,31.0,28.5.HRMS(ESI)m / z calcd forC 46 H 44 O9SN[M+NH4] + :786.2731; found:786.2718.

[0059] Example 6

[0060]

[0061] Referring to the synthesis process of S2 in Example 1, S12 (1.17 g, 2.3 mmol) was used instead of S1 to obtain S13 (1.30 g, 85%), a white foamy solid.

[0062] S13 (200 mg, 0.3 mmol) was used to replace S2 in Example 1 to obtain donor 1f (190 mg, 97%) as a white foamy solid. D 25 = +203.9 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.18-8.11(m,2H),7.98-7.89(m,2H),7.85-7.76(m,2H),7.64-7.57(m,1H),7.55-7.45(m,4H),7.45-7.32(m,4H),7.28-7. 08(m,4H),6.16(dd,J=3.3,1.2Hz,1H),5.74-5.58(m,2H),5.40(d,J=1.3 Hz,1H),3.94(dq,J=9.0,6.1Hz,1H),1.46(d,J=6.1Hz,3H),1.27(s,9H); 13 C NMR (100MHz, CDCl3) δ165.7,165.6,136.0,133.5,133.2,132.5,130.2,129.8,129.7,129.3,129.2,129.0,128.6 ,128.5,128.3,128.2,127.15,125.6,105.8,84.0,77.0,75.2,72.5,71.9,71.3,30.8,28.3,18.1.HRMS(ESI)m / z calcd for C 39 H 37 O7S[M+H] + :649.2255; found:649.2244.

[0063] Example 7

[0064]

[0065] Referring to the synthesis process of S8 in Example 4, S14 (3.5 g, 6.2 mmol) was used instead of S7 to obtain S15 (3.5 g, 90%), a white foamy solid.

[0066] S15 (1.0 g, 1.57 mmol) was used to replace S2 in Example 1 to obtain 1 g (0.95 g, 95%) of the donor as a white foamy solid. D 25 = -31.2 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.13-8.10(m,2H),8.02-7.97(m,4H),7.60(dd,J=7.9,1.3 Hz,1H),7.56-7.49(m,3H),7.43-7.29(m,7H),7.24-7.20(m,1H),7.16(td,J=7.5 ,1.3Hz,1H),5.78(dt,J=6.1,3.2Hz,1H),5.60-5.58(m,2H),5.32(td,J=5.6,3.5 Hz, 1H), 4.80 (dd, J=12.6, 3.5Hz, 1H), 3.90 (dd, J=12.5, 5.4Hz, 1H), 1.17 (s, 9H). 13 C NMR (100MHz, CDCl3) δ165.6,165.15,136.8,133.6,133.5,133.4,132.6,130.2,130.1,130.0,129.35,129.2,1 29.0,128.6,128.5,128.4,128.3,126.9,125.5,105.0,85.1,70.1,69.5,68.5,62.6,30.8,28.2; HRMS(ESI)m / z calcd for C 38 H 38 O7SN[M+NH4] + :652.2363; found:652.2355.

[0067] Example 8

[0068]

[0069] Referring to the preparation process of S2 in Example 1, S16 (1.0 g, 3.1 mmol) was used instead of S1 to obtain white foamy solid S17 (1.2 g, 84%), which was directly processed into the next step without further treatment.

[0070] Referring to the preparation process of S11 in Example 5, S17 (1.0 g, 2.2 mmol) was used instead of S10 to obtain white foamy solid S18 (1.16 g, 82%).

[0071] S18 (1.0 g, 1.5 mmol) was used to replace S2 in Example 1 to obtain donor 1h (0.86 g, 86%) as a white foamy solid. D 25 = +82.4 (c 0.5, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.06-8.00(m,6H),7.64(dd,J=7.8,1.5Hz,1H),7.60-7.50(m,3H),7.45-7.36(m,7H),7.24-7.15(m,2H),5.89(t,J =6.5Hz,1H),5.78-5.73(m,2H),5.42(d,J=6.2Hz,1H),4.59(dd,J=12.3,5.5Hz,1H),4.02(dd,J=12.3,2.7Hz,1H),1.15(d,J=1.7Hz,9H); 13 C NMR (100MHz, CDCl3) δ165.8,165.7,165.6,135.5,133.6(2C),133.6,133.4,132.8,130.4,130.2,130.0,129.9,129.65, 129.3,129.1,128.7,128.6,128.5,128.3,126.8,125.9,104.9,84.54,69.8,69.1,68.8,61.9,31.0,28.4.HRMS(ESI)m / z calcd for C 38 H 38 O7SN[M+NH4] + :652.2363; found:632.2354.

[0072] Example 9

[0073]

[0074] Referring to the synthesis process of S2 in Example 1, S19 (1.9 g, 3.8 mmol) was used instead of S1 to obtain a pair of isomers S20 (2.1 g, 84%).

[0075] S20 (1.0 g, 1.58 mmol) was used to replace S2 in Example 1 to obtain donor 1i (0.95 g, 94%) as a white foamy solid. For the β configuration: [α] D 25 = +23.6 (c 0.5, CHCl3); 1H NMR (400MHz, CDCl3) δ8.08(d,J=7.8Hz,2H),7.99(d,J=7.8Hz,2H),7.89(d,J=7.7Hz,2H),7.61(d,J=7.7Hz,1H),7.56-7.48(m,3H),7.40 -7.36(m,5H),7.31(t,J=7.7Hz,2H),7.24-7.13(m,2H),5.94-5.88(m,3H),4.75-4.69(m,2H),4.60(dd,J=11.5,4.3Hz,1H),1.28(s,9H). 13 C NMR (100MHz, CDCl3) δ166.25,165.3,165.1,135.2,133.6,133.5,133.2,132.6,131.3,129.9,129.8,129.7,129.1, 129.0,128.5(2C),128.15,127.2,126.0,105.05,87.3,80.3,75.65,72.7,72.7,64.45,30.9,28.3.; HRMS(ESI)m / z calcd for C 38 H 38 O7SN[M+NH4] + :652.2363; found:652.2333.

[0076] Example 10

[0077]

[0078] Referring to the synthesis process of S2 in Example 1, S21 (1.0 g, 1.98 mmol) was used instead of S1 to obtain S22 (1.02 g, 81%), and a white foamy solid was obtained.

[0079] S22 (1.0 g, 1.58 mmol) was used to replace S2 in Example 1 to obtain donor 1j (972 mg, 97%) as a white foamy solid. For the β configuration: [α] D 25 = -71.1 (c 0.5, CHCl3); 1H NMR (400MHz, CDCl3)) δ8.17-8.14(m,2H),8.03-8.00(m,4H),7.64-7.57(m,3H),7.51-7.46(m,3H),7.42-7.38(m,3H),7.28-7.15(m,4H),6.08( s,1H),5.79(t,J=1.2Hz,1H),5.68-5.66(m,1H),4.90(q,J=4.5Hz,1H),4.81(dd,J=12.0,3.5Hz,1H),4.74(dd,J=12.0,5.0Hz,1H),1.30(s,9H). 13 C NMR (100MHz, CDCl3)) δ166.3,165.7,165.4,135.95,133.8,133.7,133.2,132.75,130.7,130.2,130.1,129.9,129.8,1 29.2,129.0,128.7,128.4,128.3,127.0,125.8,104.85,89.7,82.8,81.6,78.4,77.3,63.6,31.0,28.4.HRMS(ESI)m / z calcd for C 38 H 38 O7SN[M+NH4] + :652.2363; found:652.2354.

[0080] Embodiment 11

[0081]

[0082] Referring to the synthesis process of S2 in Example 1, S23 (1.0 g, 1.56 mmol) was used instead of S1 to obtain white foamy solid S24 (967 mg, 81%).

[0083] S24 (1.0 g, 1.3 mmol) was used to replace S2 in Example 1 to obtain donor 1k (0.92 g, 92%) as a white foamy solid. D 25 = +40.9 (c 0.5, CHCl3); 1H NMR (600MHz, CDCl3) δ8.13-8.11(m,2H),8.00-7.99(m,2H),7.92-7.91(m,2H),7.88-7.86(m,2H),7.6 7(dd,J=7.8,1.3Hz,1H),7.61-7.58(m,1H),7.51-7.44(m,6H),7.31(t,J=7.8Hz,2H),7.28-7.22(m,5 H),7.19(td,J=7.7,1.6Hz,1H),6.05(d,J=3.5Hz,1H),5.79(dd,J=7.0,3.5Hz,1H),5.18(ddd,J=7.0, 5.3,3.2Hz,1H),4.82(dd,J=12.1,3.2Hz,1H),4.75-4.66(m,2H),4.60(d,J=12.0Hz,1H),1.25(s,9H). 13 C NMR (150MHz, CDCl3) δ166.2,165.8,165.8,165.15,136.65,133.8,133.6,133.4,133.2,133.2,131.4,130.65,130.2,129.95,129.9,129. 8,129.7(2C),129.1,128.8,128.7,128.5(2C),128.4,127.9,104.2,95.4,82.7,79.0,78.4,63.9,63.6,30.9,30.8,28.35.HRMS(ESI)m / z calcd for C 46 H 44 O9SN[M+NH4] + :786.2731; found:786.2732.

[0084] Example 12

[0085]

[0086] 1i (3.0 g, 4.73 mmol) was dissolved in CH3OH (15 mL), CH3ONa (prepared) was added, and the mixture was stirred until the substrate reaction was complete as detected by TLC. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column (CH2Cl2 / MeOH=40:1) to obtain the triol intermediate (white solid, 1.42 g, 93%). The mixture was directly transferred to the next step without further treatment.

[0087] The above intermediate (1.4 g, 4.34 mmol) was dissolved in dry pyridine (20 mL), CCl4 (7.54 mL, 82.5 mmol) and PPh3 (3.98 g, 15.2 mmol) were added at room temperature, and stirred until the substrate reaction was complete as detected by TLC. After dilution with EtOAc, the mixture was washed with 1M HCl and saturated brine in sequence, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (CH2Cl2 / MeOH=50:1) to obtain S26 (1.29 g, 87%) as a colorless liquid. [α] D 25 = -79.0 (c 0.85, CHCl3); 1 HNMR (600MHz, CD3OD) δ7.63-7.47(m,1H),7.31(dd,J=7.7,1.6Hz,1H),7.24(td,J=7.7,1.6Hz,1H),7.21-7.06(m,1H),5.44(d,J=3.5Hz,1H ),4.19(t,J=5.4Hz,1H),4.16-4.08(m,2H),3.73(dd,J=11.8,4.8Hz,1H),3.66(dd,J=11.8,5.4Hz,1H),3.30(p,J=1.6Hz,1H),1.33(s,9H); 13 C NMR (150MHz, CD3OD) δ138.5,133.2,130.8(2C),129.2,127.3,125.9,105.3,90.3,85.0,78.35,77.0,73.8,45.8,31.3,29.3.HRMS(ESI)m / z calcd forC 17 H 22 ClO3S[M+H] + :341.0973; found:341.0968.

[0088] S26 (1.2 g, 3.52 mmol) was dissolved in dry pyridine (18 mL), BzCl (1.23 mL, 10.56 mmol) was added at 0 °C, the temperature was raised to room temperature, and the reaction was stirred until the substrate reaction was complete as detected by TLC. EtOAc was added for dilution, and the mixture was washed with 1 M HCl and saturated brine in sequence, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / ethyl acetate = 40:1) to obtain donor 1n (1.45 g, 75%) as a white solid. [α] D 25 = -31.5 (c 0.45, CHCl3); 1H NMR (400MHz, CDCl3) δ7.99-7.94(m,2H),7.92-7.86(m,2H),7.62(dd,J=7.8,1.3Hz,1H),7.58-7.49(m,2H),7.43-7.30(m,5 H),7.18(d,J=1.3Hz,2H),5.86(d,J=2.9Hz,1H),5.83-5.74(m,2H),4.65-4.50(m,1H),3.86(d,J=5.4Hz,2H),1.29(s,9H). 13 C NMR (100MHz, CDCl3) δ165.4,165.1,135.3,133.65,132.8,131.2,130.0,129.9,129.1,129.0 ,128.6,128.3,127.3,126.0,105.2,87.4,82.5,75.7,73.6,44.6,30.95,28.4.HRMS(ESI)m / z calcd forC 31 H 33 ClO5SN[M+NH4] + :566.1762; found:566.1744.

[0089] Part II: Receptor Synthesis

[0090] Example 13

[0091]

[0092] Process a: Add purine (2a'-2f') (1 eq) and DMAP (0.2 eq) to dry THF (0.25 M), then add Boc2O (6 eq), stir until TLC detects that the substrate reaction is complete, add CH3OH to quench the reaction, add EtOAc to dilute, wash with saturated NaHCO3 solution, dry over anhydrous Na2SO4, filter and concentrate by rotary evaporation, and purify by silica gel column (petroleum ether / ethyl acetate = 15:1) to obtain three Boc-protected purines.

[0093] Three Boc-protected purines (1 eq) were dissolved in CH3OH (5 M), and saturated NaHCO3 solution was added. Stir at 50°C for 0.5 h, and diluted with EtOAc. The mixture was washed with water and saturated brine in turn, dried over anhydrous Na2SO4, filtered, concentrated by rotary evaporation, and purified by silica gel column (petroleum ether / dichloromethane / ethyl acetate = 1:1:1) to obtain two Boc-protected purine receptors (2a-2f).

[0094] Among them, 2a and 2d are known compounds.

[0095] 2b' (500 mg, 3.3 mmol) was prepared according to procedure a to give 2b (730 mg, 63%) as a white solid. 1 H NMR (600MHz, CDCl3) δ8.42 (s, 1H), 1.55 (s, 18H). 13 C NMR(150MHz, CDCl3)δ158.6,157.15,149.7,145.4,85.95,28.1,27.8.HRMS(ESI)m / z calcd for C 15 H 21 FO5N4[M+H] + :354.1572; found:354.1573.

[0096] 2c' (500 mg, 2.9 mmol) was prepared according to procedure a to give 2c (775 mg, 56%) as a white solid. 1 H NMR (400MHz, CDCl3) δ8.43 (s, 1H), 1.54 (s, 18H). 13 C NMR(100MHz, CDCl3)δ152.9,149.8,145.2,85.7,28.15,27.8.HRMS(ESI)m / z calcd for C 15 H 21 ClO5N4[M+H] + :370.1277; found:370.1272.

[0097] 2e' (500 mg, 2.3 mmol) was prepared according to process a to give a white solid 2e (406 mg, 42%): 1 H NMR (600MHz, CDCl3) δ8.39 (s, 1H), 1.49 (s, 18H). 13 C NMR(150MHz, CDCl3)δ151.4,150.8,145.2,84.7,28.0.HRMS(ESI)m / z calcd for C 15 H 21 BrO5N4[M+H] + :414.0772; found:414.0775.

[0098] 2f' (500 mg, 1.9 mmol) was prepared according to procedure a to give 2f (322 mg, 48%) as a white solid. 1H NMR (600MHz, CDCl3) δ12.85(s,1H),8.37(s,1H),1.52(s,18H). 13 C NMR (150MHz,CDCl3)δ

[0099] 151.1,150.8,149.0,144.55,136.75,121.8,84.7,28.0.HRMS(ESI)m / z calcdfor C 15 H 21 IO5N4[M+H] + :462.0633; found:462.0629.

[0100] Embodiment 14

[0101]

[0102] Process b: Pyrimidine (4a'-4c') (1 g, 7.9 mmol) and DMAP (0.02 eq) were added to dry CH3CN (0.3 M), and Boc2O (1.04 eq) was added at 0°C. The mixture was warmed to room temperature and stirred until the substrate reaction was complete as detected by TLC. After rotary evaporation and concentration, the mixture was dissolved in DMF (0.3 M) at 0°C. NaH (1.2 eq) and PMBCl (1.2 eq) were added at 0°C. The mixture was slowly warmed to room temperature and stirred for 1 h. The mixture was poured into an ice-water mixture and precipitated with E The organic phase was extracted with tOAc, and the organic phase was dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation to obtain a crude product. The crude product was added to methanol (0.2M), K2CO3 (0.5eq) was added, and stirred at room temperature for 2h. The reaction was complete after TLC detection. The solvent was evaporated in vacuo, and the residue was dissolved in dichloromethane, washed with saturated NH4Cl solution, dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation. The receptors 4a-4c were purified by silica gel column (petroleum ether / ethyl acetate = 4:1).

[0103] 4a' (1.0 g, 8.92 mmol) was prepared according to procedure b to give 4a (1.5 g, 72%) as a white solid. 1 H NMR (400MHz, CDCl3) δ10.02 (s, 1H), 7.47-7.34 (m, 2H), 7.11 (dd, J = 7.7, 5.7Hz, 1H),6.90-6.69(m,2H),5.77(dd,J=7.7,1.7Hz,1H),5.03(s,2H),3.77(s,3H). 13C NMR(100MHz, CDCl3)δ163.3,159.3,153.2,138.4,130.6,128.9,113.9,102.4,55.4,43.3.HRMS(ESI)m / zcalcd forC 12 H 13 O3N2[M+H] + :233.0921; found:233.0916.

[0104] 4b' (1.0 g, 7.93 mmol) was prepared according to procedure b to give 4b (1.60 g, 82%) as a white solid. 1 H NMR(400MHz, CDCl3)δ10.13(d,J=5.6Hz,1H),7.52-7.31(m,2H),6.97(dd,J=5.6 ,1.3Hz,1H),6.90-6.66(m,2H),5.05(s,2H),3.77(s,3H),1.91(d,J=1.2Hz,3H). 13 C NMR(100MHz, CDCl3)δ164.1,159.2,153.5,134.6,130.6,129.1,113.9,110.4,55.4,43.5,13.1.HRMS(ESI)m / z calcd for C 13 H 15 O3N2[M+H] + :247.1077; found:247.1072.

[0105] 4c' (1.0 g, 7.69 mmol) was prepared according to procedure b to give 4c (1.50 g, 78%) as a white solid. 1 H NMR (400MHz, CDCl3) δ9.98(d,J=5.8Hz,1H),7.41(d,J=8.7Hz,2H),7.20(dd,J=6.1,4.2Hz,1H),6.87-6.78(m,2H),5.05(s,2H),3.78(s,3H). 13 C NMR(100MHz, CDCl3)δ159.5,157.7,157.4,151.8,142.0,139.7,130.8,128.1,122.85,122.5,114.0,55.4,44.2.HRMS(ESI)m / zcalcd for C 12 H 11 FO3N2Na[M+Na] +:273.0646; found:273.0639.

[0106] It is a known compound and can be prepared by referring to the prior art.

[0107] Part III: N-glycosylation process of purine or pyrimidine (eluent is ethyl acetate and petroleum ether in a volume ratio of 1:3 to 1:1) Process A: donor (1.2 eq, 30-60 mM), acceptor (1.0 eq), Molecular sieves (0.5 g / mmol based on the amount of receptor) were added to dry CH2Cl2 and stirred for 15 min. PPh3AuNTf2 (0.02-0.2 eq) was added at room temperature and stirred until the substrate reaction was complete as detected by TLC. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column to obtain the corresponding product.

[0108] Process B: donor (1.2eq, 24mM), acceptor (1.0eq), Molecular sieves (based on the amount of receptor, 0.5 g / mmol) were added to dry CH2Cl2 and HFIP (V DCM / V HFIP =4:1) in a mixed solvent, stirred for 15 min, added PPh3AuNTf2 (0.02-0.2 eq) at room temperature, stirred until the substrate reaction was complete as detected by TLC, filtered and concentrated by rotary evaporation, and purified by silica gel column to obtain the corresponding product.

[0109] Process C: Add donor (1.0 eq), acceptor (2 eq, 50 mM), CH2Cl2 and BSTFA (4 eq) into a sealed tube and stir at 80 °C until the reaction solution becomes clear (about 8 h). After cooling to room temperature, add Molecular sieves (based on the amount of receptor, 0.5 g / mmol) and PPh3AuNTf2 (0.02-0.2 eq) were added and stirred until the substrate reaction was complete as detected by TLC. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column to obtain the corresponding product.

[0110] Application Example 1

[0111]

[0112] The donor 1a (62 mg, 0.12 mmol), the acceptor 2a (34 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were dissolved in dry CH2Cl2 (3 mL) and reacted according to process A for 4 h to obtain 3aa (34 mg, 52%) and 3aa' (28 mg, 42%). 3aa was a white solid: [α] D 25 = -8.0 (c 1.0, CHCl3);1 H NMR (400MHz, CDCl3) δ8.87(s,1H),8.26(s,1H),5.97(d,J=9.5Hz,1H,H-1'),5.62(t,J=9.5Hz,1H),5.47(t,J=9.4Hz,1H),5.30(t,J=9.8Hz,1H), 4.30(dd,J=12.6,4.9Hz,1H),4.15(dd,J=12.6,2.2Hz,1H),4.08-4.02(m ,1H),2.08(s,3H),2.07(s,3H),2.03(s,3H),1.72(s,3H),1.44(s,18H); 13 CNMR (150MHz, CDCl3) δ170.6,170.0,169.5,169.0,153.2,152.7,150.9,150.4,142.2, 128.6,84.1,80.7(C-1'),75.3,72.9,70.4,67.9,61.7,27.9.20.6,20.2.HRMS(ESI)m / z calcdfor C 29 H 39 N5O 13 Na[M+Na] + :688.2437; found:688.2451.

[0113] 3aa' is a white solid: [α] D 25 =-4.9(c 0.5,CHCl3); HRMS(ESI)m / z calcd forC 24 H 32 N5O 11 [M+H] + :566.2093; found:566.2110.

[0114] Application Example 2

[0115]

[0116] Donor 1a (62 mg, 0.12 mmol), acceptor 2b (35 mg, 0.1 mmol) and catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were added to dry CH2Cl2 (3 mL) and reacted according to process A for 4 h to obtain 3ab (31.1 mg, 46%) and 3ab' (30.1 mg, 52%). 3ab was a white solid: [α] D 25 = -12.5 (c 1.25, CHCl3);1 HNMR (400MHz, CDCl3) δ8.21(s,1H),5.85(d,J=9.4Hz,1H,H-1'),5.57(t,J=9.5Hz,1H),5.44(t,J=9.4Hz,1H),5.27(t,J=9.8Hz,1H),4.29(dd ,J=12.6,4.9Hz,1H),4.15(dd,J=12.6,2.1Hz,1H),4.03(ddd,J=10.2,5.0,2.2Hz,1H),2.07(s,6H),2.02(s,3H),1.76(s,3H),1.46(s,18H); 13 CNMR (100MHz, CDCl3) δ170.6,169.9,169.5,169.05,159.3,157.1,155.1,154.9,152.55,149.85,142.4,14 2.4,126.6,84.65,80.7(C-1'),75.35,72.8,70.3,67.8,61.6,27.8,20.8,20.7,20.6,20.2.HRMS(ESI)m / z calcd for C 29 H 38 F5O 13 Na[M+Na] + :706.2342; found:706.2342.3ab' is a white solid: [α] D 25 =-5.0(c 1.0,CHCl3); HRMS(ESI)m / zcalcd forC 24 H 30 F5O 11 Na[M+Na] + :606.1818; found:606.1818.

[0117] Application Example 3

[0118]

[0119] Donor 1a (62 mg, 0.12 mmol), acceptor 2c (37 mg, 0.1 mmol) and catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were added to dry CH2Cl2 (3 mL) and reacted according to process A for 4 h to obtain 3ac (34 mg, 49%) and 3ac' (24 mg, 40%). 3ac was a white solid: [α] D 25 = -5.5 (c 1.5, CHCl3);1 H NMR (400MHz, CDCl3) δ8.25(s,1H),5.91(d,J=9.3Hz,1H,H-1'),5.53(t,J=9.4Hz,1H),5.45(t,J=9.4Hz,1H),5.27(dd,J=10.1,9.2Hz,1H),4.28 (dd,J=12.7,4.9Hz,1H),4.14(dd,J=12.6,2.2Hz,1H),4.04(ddd,J=10.2,4.9,2.2Hz,1H),2.07(s,6H),2.01(s,3H),1.75(s,3H),1.43(s,18H); 13 C NMR (100MHz, CDCl3) δ170.6,169.9,169.5,169.1,154.5,153.5,151.6,149.8,142.5,127.2,8 4.5,80.5(C-1'),75.3,72.7,70.4,67.7,61.55,27.8,20.8,20.65,20.6,20.16; HRMS(ESI)m / z calcd for C 29 H 38 ClN5O 13 [M+Na] + :722.2047; found:722.2060.3ac' as white solid; HRMS (ESI) m / z calcd for C 24 H 30 ClN5O 11 Na[M+Na] + :622.1523; found:622.1522.

[0120] Application Example 4

[0121]

[0122] The donor 1a (62 mg, 0.12 mmol), the acceptor 2d (37 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were dissolved in dry CH2Cl2 CH2Cl2 (3 mL) and reacted for 4 h according to process A to obtain 3ad (38 mg, 54%) and 3ad' (10 mg, 17%). 3ad was a white solid: [α] D 25 = +6.6 (c 1.9, CHCl3); 1H NMR (400MHz, CDCl3) δ8.34(s,1H),5.89(d,J=9.2Hz,1H,H-1'),5.52(t,J=9.3Hz,1H),5.45(t,J=9.3Hz,1H),5.27(dd,J=10.2,9.1Hz,1H),4.29 (dd,J=12.6,5.1Hz,1H),4.13(dd,J=12.6,2.2Hz,1H),4.02(ddd,J=10.1,5.0,2.2Hz,1H),2.07(s,6H),2.02(s,3H),1.77(s,3H),1.47(s,18H); 13 C NMR (100MHz, CDCl3) δ170.6,170.0,169.5,169.3,152.6,152.5,152.0,150.85,143.6,129.9, 84.1,80.8(C-1'),75.4,72.7,70.5,67.8,61.6,28.0,20.8,20.65,20.6,20.1.HRMS(ESI)m / z calcd for C 29 H 39 ClN5O 13 [M+H] + :700.2227; found:700.2227.3ad' is a white solid: [α] D 25 =+3.4(c 1.0,CHCl3); HRMS(ESI)m / z calcd for C 24 H 31 ClN5O 11 [M+H] + :600.1703; found:600.1698.

[0123] Application Example 5

[0124]

[0125] The donor 1a (62 mg, 0.12 mmol), the acceptor 2e (41 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were dissolved in dry CH2Cl2 (3 mL) and reacted for 4 h according to process A to obtain 3ae (73 mg, 98%) as a white solid: [α] D 25 = +5.9 (c 1.5, CHCl3); 1H NMR (400MHz, CDCl3) δ8.35(s,1H),5.88(d,J=9.2Hz,1H,H-1'),5.52(t,J=9.4Hz,1H),5.45(t,J=9.4Hz,1H),5.27(t,J=9.6Hz,1H),4.29(dd ,J=12.6,5.0Hz,1H),4.13(dd,J=12.6,2.1Hz,1H),4.01(ddd,J=10.2,5.0,2.2Hz,1H),2.06(s,6H),2.02(s,3H),1.78(s,3H),1.47(s,18H); 13 C NMR (100MHz, CDCl3) δ170.6,170.0,169.45,169.25,152.4,151.35,150.8,143.8,143.4,132.5, 84.05,80.8(C-1'),75.4,72.7,70.5,67.8,61.6,28.05,20.8,20.65,20.6,20.1; HRMS(ESI)m / z calcd forC 29 H 38 BrN5O 13 Na[M+Na] + :766.1542; found:766.1545.

[0126] Application Example 6

[0127]

[0128] The donor 1a (62 mg, 0.12 mmol), the acceptor 2f (46 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were dissolved in dry CH2Cl2 (3 mL) and reacted according to process A for 4 h to obtain 3af (61 mg, 77%), which was a white solid: [α] D 25 = +3.4 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.53(s,1H),8.03-7.97(m,2H),7.96-7.91(m,2H),7.83-7.78(m,2H),7.78-7. 70(m,2H),7.57-7.49(m,2H),7.46-7.32(m,6H),7.31-7.21(m,4H),6.25(d,J=9.2Hz,1H,H-1'),6.20

[0129] -6.09(m,2H),5.96-5.87(m,1H),4.72-4.61(m,1H),4.55-4.46(m,2H),1.38(s,18H); 13 C NMR (100MHz, CDCl3) δ166.1,165.7,165.2,165.0,152.25,150.5,149.0,143.1,136.75,133.9,133.8,133.65,133.4,130.1,130.0,129. 95,129.9,129.8,129.3,128.6,128.6,128.5,128.4,127.6,121.9,83.7,80.8(C-1'),75.7,73.2,70.8,68.9,62.6,27.9; HRMS(ESI)m / z calcd for C 29 H 38 IN5O 13 Na[M+Na] + :814.1403; found:814.1425.

[0130] Application Example 7

[0131]

[0132] The donor 1b (46.2 mg, 0.06 mmol), the acceptor 2e (20.7 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3be (29.3 mg, 59%) and 3be' (14.7 mg, 33%). 3be was a white solid: [α] D 25 = +16.8 (c 1.1, CHCl3); 1 HNMR(400MHz, CDCl3)δ8.53(s,1H),8.04-7.96(m,2H),7.96-7.88(m,2H) ,7.84-7.77(m,2H),7.77-7.69(m,2H),7.58-7.47(m,2H),7.46-7.32(m, 6H),7.29-7.25(m,4H),6.27(d,J=8.6Hz,1H,H-1'),6.19-6.09(m,2H),5 .91(t,J=9.2Hz,1H),4.74-4.59(m,1H),4.58-4.42(m,2H),1.37(s,18H); 13C NMR (100MHz, CDCl3) δ166.1,165.7,165.2,165.0,152.4,151.5,150.4,143.7,143.5,134.0,133.85,133.7,133.4,132.4,130.1,13 0.0,129.9,129.8,129.3,128.6,128.6,128.5,128.4,127.6,83.8,80.9(C-1'),75.7,73.1,70.85,68.9,62.6,27.9.HRMS(ESI)m / z calcd for C 49 H 47 BrN5O 13 [M+H] + :992.2348; found:992.2377.3be' is a white solid: [α] D 25 =+30.2(c 1.0,CHCl3); HRMS(ESI)m / z calcd for C 44 H 38 BrN5O 11 Na[M+Na] + :914.1634; found:914.1652.

[0133] Application Example 8

[0134]

[0135] The donor 1c (87.2 mg, 0.12 mmol), the acceptor 2c (36.7 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted for 8 h according to process A to obtain 3cc' (74.2 mg, 92%), which was a white solid: [α] D 25 = +29.4 (c 1.8, CHCl3); 1H NMR(400MHz, CDCl3)δ8.23(s,1H),7.96(s,1H),7.88-7.70(m,2H),7.57-7.44(m,1H),7.3 7-7.27(m,10H),7.24-7.20(m,2H),7.17-7.04(m,5H),5.92(d,J=9.4Hz,1H,H-1'),5.64(t ,J=9.1Hz,1H),4.88(d,J=10.8Hz,1H),4.79(d,J=11.2Hz,1H),4.73-4.62(m,2H),4.58(d, J=12.1Hz,1H),4.52(d,J=12.1Hz,1H),4.07-3.95(m,2H),3.88-3.68(m,3H),1.52(s,9H); 13 C NMR (100MHz, CDCl3) δ165.1,154.55,152.3,150.6,149.0,140.8,137.75,137.7,137.4,133.8,129.9,128.7,128.6(3C),128.5,128. 4(2C),128.3,128.2(2C),128.1,128.0(2C),127.9,120.1,82.8,82.65,80.8,78.5,75.6,75.4,73.7,73.4,68.2,28.2.HRMS(ESI)m / z calcd for C 44 H 45 ClN5O8[M+H] + :628.1593; found:628.1588.

[0136] Application Example 9

[0137]

[0138] The donor 1d (46.2 mg, 0.06 mmol), the acceptor 2d (18.5 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3dd (43.6 mg, 92%), 3dd as a white solid: [α] D 25 = +89.0 (c 2.0, CHCl3); 1H NMR (400MHz, CDCl3) δ8.60 (s, 1H), 8.15 (d, J = 7.6Hz, 2H), 7.98 (d, J = 7.7Hz, 2H), 7.81-7.72 (m, 4H),7.69(t,J=7.4Hz,1H),7.61-7.51(m,3H),7.45-7.37(m,4H),7.29-7.21(m,4H),6.44(t,J= 9.6Hz,1H),6.29(d,J=9.5Hz,1H,H-1'),6.21(d,J=3.2Hz,1H),5.95(dd,J=10.1,3.4Hz,1H),4 .73(t,J=6.2Hz,1H),4.65(dd,J=11.5,6.4Hz,1H),4.50(dd,J=11.5,5.8Hz,1H),1.37(s,18H); 13 C NMR (100MHz, CDCl3) δ166.0,165.4,165.3,165.0,152.8,152.5,151.7,150.35,144.1,134.1,133.9,133.6,133.45,129.9(3C),129. 8(2C),129.1,129.05,128.7,128.5,128.4(2C),128.3,127.7,83.7,81.5(C-1'),74.7,71.85,68.6,68.0,61.9,27.8; HRMS(ESI)m / z calcdfor C 49 H 47 ClN5O 13

[0139] [M+H] + :948.2853; found:948.2845.

[0140] Application Example 10

[0141]

[0142] The donor 1e (46.2 mg, 0.06 mmol), the acceptor 2c (18.5 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3ec (23.2 mg, 49%) and 3ec' (20.4 mg, 48%). 3ec was a white solid: [α] D 25 = +65.5 (c 1.25, CHCl3); 1HNMR(400MHz, CDCl3)δ8.39(s,1H),8.26-8.17(m,2H),8.17-8.06(m,2H),8.06-7.97(m,2H), 7.85-7.75(m,2H),7.66-7.61(m,2H),7.58-7.48(m,6H),7.43-7.37(m,2H),7.34-7.28(m,2H ),6.76(dd,J=7.6,3.3Hz,1H),T,6.20(dd,J=5.2,3.4Hz,1H),5.81(t,J=4.5Hz,1H),5.38(dd ,J=12.3,8.5Hz,1H),4.74(dt,J=8.1,3.7Hz,1H),4.51(dd,J=12.3,3.5Hz,1H),1.35(s,18H); 13 CNMR (100MHz, CDCl3) δ166.6,165.3,165.1,164.7,154.5,153.55,151.7,149.8,144.4,134.1,133.9,133.6,130.3,130.0,129.9(2C ),129.3,129.0,128.9,128.75,128.7,128.65,128.35,128.1,84.3,78.9(C-1'),75.6,69.1,68.0,67.4,60.9,27.75; HRMS(ESI)m / z calcd for C 49 H 47 ClN5O 13 [M+H] + :948.2853; found:948.2833.

[0143] 3ec' is a white solid: HRMS (ESI) m / z calcd for C 44 H 39 ClN5O 11 [M+H] + :848.2329; found:848.2310. Application Example 11

[0144]

[0145] The donor 1f (77.8 mg, 0.12 mmol), the acceptor 2d (37.0 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (3.5 mg, 0.0048 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 8 h according to process A to obtain 3fb' (61.9 mg, 87%). 3fb' was a white solid: [α]D 25 = -29.4 (c 1.5, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.30(s,1H),8.24(s,1H),8.15-8.09(m,2H),8.08-7.98(m, 2H),7.87-7.80(m,2H),7.66-7.57(m,2H),7.56-7.43(m,5H),7.38-7.29(m,2H), 6.45(d,J=6.9Hz,1H,H-1'),6.31(dd,J=6.9,3.4Hz,1H),6.07(dd,J=5.3,3.5Hz, 1H),5.54(t,J=4.8Hz,1H),4.59-4.42(m,1H),1.67(d,J=6.7Hz,3H),1.54(s,9H). 13 C NMR (100MHz, CDCl3) δ165.4,165.3,165.1,160.0,157.9,153.0,152.8,152.0,151.85,149.1,141.0,133.95,130.1,130. 0,129.9,129.0,128.9,128.8,128.7,128.3,119.8(2C),83.1,73.1,71.9,69.7,68.7,28.2,16.8.HRMS(ESI)m / zcalcdfor C 37 H 35 FN5O9[M+H] + :712.2413; found:712.2384.

[0146] Application Example 12

[0147]

[0148] The donor 1f (38.9 mg, 0.06 mmol), the acceptor 2d (18.5 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3fd (15.3 mg, 37%) and 3fd' (22.6 mg, 62%).

[0149] The donor 1f (77.8 mg, 0.12 mmol), the acceptor 2d (37 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 48 h according to process A to obtain 3fd' (55.3 mg, 76%), which was a white solid: [α] D 25 = +21.1 (c 0.85, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.21(s,1H),8.10(s,1H),8.05-8.01(m,4H),7.99-7.93(m,2H),7.62-7.48(m,3H),7.48-7.32(m,6H),6.70(t,J=3.7Hz ,1H),6.38(dd,J=8.0,3.6Hz,1H),6.28(d,J=3.7Hz,1H,H-1'),5.70(t,J=7.9Hz,1H),4.32-4.15(m,1H),1.52(s,9H),1.49(d,J=6.4Hz,3H); 13 C NMR (100MHz, CDCl3) δ165.65,165.5,165.4,153.0,152.5,152.3,150.1,143.3,133.95,133.7,133.6,130.1,130.0(2 C),129.05,129.0,128.7,128.7(2C),128.6,127.9,81.5(2C,C-1'),71.6,71.3,70.5,69.2,28.3,17.4; HRMS(ESI)m / z calcd for C 37 H 35 ClN5O9[M+H] + :728.2118; found:728.2116.

[0150] Application Example 13

[0151]

[0152] The donor 1g (38.1 mg, 0.06 mmol), the acceptor 2b (17.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3gb (14.0 mg, 35%) and 3gb' (20.6 mg, 59%). 3gb was a white solid: [α] D 25= +85.0 (c 1.0, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.35(s,1H),8.28-8.15(m,2H),7.89-7.80(m,2H),7.76-7.70(m, 2H),7.71-7.64(m,1H),7.60-7.53(m,2H),7.49-7.41(m,2H),7.32-7.27(m,4H),6.55- 6.38(m,1H),6.02(d,J=9.3Hz,1H,H-1'),5.90(dd,J=3.1,1.7Hz,1H),5.81(dd,J=10.1 ,3.4Hz,1H),4.50(dd,J=13.5,2.0Hz,1H),4.22(dd,J=13.6,1.2Hz,1H),1.36(s,18H); 13 C NMR (100MHz, CDCl3) δ165.7,165.5,165.0,157.0,154.9,152.7,152.5,150.0,142.9,142.9,134.0(2C),133.7,130 .1,129.9,129.8,129.3,129.0,128.6(2C),127.8,84.4,82.5(C-1'),71.75,68.9,68.85,67.7,27.7; HRMS(ESI)m / z calcd for C 41 H 41 F5O 11 [M+H] + :798.2781; found:798.2778.3gb' is a white solid: [α] D 25 =+98.9(c 1.0,CHCl3); HRMS(ESI)m / z calcd forC 36 H 33 FN5O9[M+H] + :698.2257; found:698.2249.

[0153] Application Example 14

[0154]

[0155] The donor 1g (38.1 mg, 0.06 mmol), the acceptor 2d (18.5 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3gd' (32.5 mg, 91%), 3gd' was a white solid: [α] D 25 = +206.4 (c 1.35, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.34(s,1H),8.22-8.11(m,2H),7.91-7.82(m,2H),7.8 2-7.74(m,2H),7.72-7.62(m,1H),7.56(t,J=7.7Hz,2H),7.51-7.38(m,3H),7 .35-7.19(m,4H),6.29(t,J=9.5Hz,1H),6.14(d,J=9.2Hz,1H,H-1'),5.96-5. 73(m,2H),4.49(dd,J=13.5,1.9Hz,1H),4.25(d,J=13.5Hz,1H),1.58(s,9H); 13 C NMR (100MHz, CDCl3) δ165.7,165.5,165.2,152.85,152.8,151.7,150.0,141.9,133.9,133.8,133.7,130.0(2C),129.9,12 9.4,128.9,128.7,128.55,128.45,128.0,127.65,81.95,81.9(C-1'),71.65,69.4,69.1,67.7,28.4; HRMS(ESI)m / zcalcd for C 36 H 33 ClN5O9[M+H] + :814.2486; found:814.2479.

[0156] Application Example 15

[0157]

[0158] The donor 1h (38.1 mg, 0.06 mmol), the acceptor 2a (16.8 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3ha (20.2 mg, 52%) and 3ha' (15.3 mg, 45%), 3ha is a known compound.

[0159] 3ha' is a white solid: [α] D 25 = -4.9 (c 0.85, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.68(s,1H),8.29(s,1H),8.04-7.94(m,2H),7.92-7.81(m,2H),7.77 -7.64(m,2H),7.62-7.51(m,1H),7.51-7.37(m,4H),7.31(t,J=7.8Hz,2H),7.28-7.21(m,2 H),6.16(d,J=9.2Hz,1H,H-1'),6.13(t,J=9.2Hz,1H),6.03(t,J=9.4Hz,1H),5.62(td,J=1 0.0,5.6Hz,1H),4.61(dd,J=11.6,5.6Hz,1H),3.89(dd,J=11.6,10.4Hz,1H),1.53(s,9H); 13 C NMR(100MHz, CDCl3)δ165.7(2C),165.0,153.5,151.1,150.1,149.6,140.2,133.9,133.8,133.6,130.0,129.9 ,128.7(2C),128.55,128.5,127.8,121.3,82.5,81.6(C-1'),72.7,71.2,69.7,66.3,28.2;28.2;HRMS(ESI)m / z calcd for C 36 H 34 N5O9[M+H] + :680.2351; found:680.2361.

[0160] Application Example 16

[0161]

[0162] Donor 1i (38 mg, 0.06 mmol), acceptor 2b (17.6 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 3ib (29.9 mg, 75%) and 3ib' (7 mg, 20%).

[0163] Donor 1i (76.1 mg, 0.12 mmol), acceptor 2b (35.3 mg, 0.1 mmol) and catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted according to process A for 48 h to obtain 3ib' (65.6 mg, 94%).

[0164] 3ib is a white solid: [α] D 25 = -44.0 (c 1.5, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.20(s,1H),8.16-8.06(m,2H),8.06-7.98(m,2H),7.9 8-7.84(m,2H),7.65-7.52(m,3H),7.52-7.32(m,6H),6.46(d,J=5.6Hz,1H,H -1'),6.19(t,J=5.7Hz,1H),6.13(dd,J=5.8,4.2Hz,1H),4.89(dd,J=12.0,3 .2Hz,1H),4.83(q,J=3.8Hz,1H),4.74(dd,J=12.1,4.0Hz,1H),1.45(s,18H); 13 CNMR (100MHz, CDCl3) δ166.3,165.4,165.2,154.9,152.7,152.5,149.95,143.2,143.15,134.1,133.99,133.7,130.0 ,129.9,129.3,128.9,128.8,128.7(2C),128.3,127.4,86.6(C-1'),84.6,81.2,74.2,71.5,63.7,27.9.HRMS(ESI)m / z calcd forC 41 H 41 F5O 11 [M+H] + :798.2781; found:798.2798.3ib' is a white solid: [α] D 25 =-67.2(c 1.6,CHCl3); HRMS(ESI)m / z calcd for C 36 H 33 FN5O9[M+H] + :698.2257; found:698.2267.

[0165] Application Example 17

[0166]

[0167] The donor 1j (38 mg, 0.06 mmol), the acceptor 2a (16.8 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted for 4 h according to process A. After the acceptor reaction was detected to be complete, silica gel was added and stirred for 8 h to obtain 3ja' (25 mg, 74%). 3ja' was a white solid: [α] D 25 = +2.0 (c 1.05, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.78(s,1H),8.23(s,1H),8.08(d,J=7.8Hz,2H),8.04(d,J=7.8Hz,2H),7.91(d,J=7.7Hz,2H),7.64-7. 40(m,8H),7.37(t,J=7.6Hz,2H),6.54(t,J=2.6Hz,1H),6.50(d,J=2.4Hz,1H,H-1'),5.91(dd,J=4.5,2.7Hz,1H),5.11(q,J=

[0168] 4.7Hz, 1H), 4.79 (d, J = 4.6Hz, 2H), 1.57 (s, 9H). 13 C NMR (100MHz, CDCl3) δ166.25,165.55,165.5,153.4,150.9,150.2,149.75,141.1,134.1,134.05,133.45,130.2 ,129.9,129.5,128.8(2C),128.6,128.4,122.2,89.4(C-1'),83.3,82.5,80.7,63.7,29.8,28.3; HRMS(ESI)m / z calcd for C 36 H 34 N5O9[M+H] + :680.2351; found:680.2351.

[0169] Application Example 18

[0170]

[0171] The donor 1k (46 mg, 0.06 mmol), the acceptor 2a (16.8 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 4 h to obtain 3ka (33.4 mg, 73%) and 3ka' (9.4 mg, 23%). 3ka was a white solid: [α] D 25 = +8.4 (c 1.0, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.83(s,1H),8.53(s,1H),8.12-8.06(m,2H),8.05-8.00( m,2H),7.80-7.74(m,2H),7.66-7.60(m,1H),7.55(d,J=1.2Hz,1H,H-3'),7.54 -7.43(m,6H),7.36-7.28(m,8H),5.76(dd,J=3.2,1.3Hz,1H,H-4'),5.11-5.04 (m,2H,H-1'),4.87-4.83(m,2H,H-6'),4.82-4.75(m,1H,H-5'),1.38(s,18H); 13 C NMR (100MHz,CDCl3)δ

[0172] 166.25,165.4,165.2,164.6,152.8,152.4,151.0,150.5,142.8,134.2 ,133.8,133.6,133.4,130.2,129.9,129.8,129.6,129.45,129.0,128. 9,128.7,128.55,128.5,128.4,128.1,97.9(C-2'),84.6(C-5'),83.9, 78.7(C-3'),78.0(C-4'),64.6(C-1'),63.5(C-6'),27.8; HRMS(ESI)m / z calcd for C 49 H 48 N5O 13 [M+H] + :914.3243; found:914.3241.

[0173] 3ka' is a white solid: [α] D 25 =+4.4(c 0.8,CHCl3); HRMS(ESI)m / z calcd forC 44 H 39N5O 11 [M+Na] + :836.2538; found:836.2531.

[0174] Application Example 19

[0175]

[0176] The donor 1k (92.4 mg, 0.12 mmol), the acceptor 2d (37 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (17.7 mg, 0.024 mmol) were dissolved in dry CH2Cl2 (3 mL) and reacted according to process A for 4 h to obtain 3kd (16.1 mg, 17%) and 3kd' (66.2 mg, 78%). 3kd was a white solid: [α] D 25 =-12.5(c 1.0,CHCl3); HRMS(ESI)m / z calcdfor C 49 H 46 ClN5O 13 Na[M+Na] + :970.2673; found:970.2673.

[0177] 3kd' is a white solid: [α] D 25 = -9.0 (c 1.0, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.40(s,1H),8.15-8.07(m,2H),8.07-7.96(m,2H),7.86-7.76(m,2H),7.68-7.60(m, 1H),7.59-7.42(m,6H),7.40-7.27(m,9H),5.78-5.64(m,1H),5.04(s,2H),4.92-4.71(m,3H),1.49(s,9H); 13 CNMR (150MHz, CDCl3) δ166.2,165.35,164.8,164.6,152.4,152.2,152.0,149.6,142.1,134.3,134.1,133.7,133.5,130.1,129. 9,129.8,129.3,129.05,128.9,128.7,128.6(2C),128.5,128.4,128.0,97.7,84.2,81.8,77.5,64.2,63.4,28.3; HRMS(ESI)m / z calcd forC 44 H38 ClN5O 11 Na[M+Na] + :870.2149; found:870.2149.

[0178] Application Example 20

[0179]

[0180] Donor 1b (46.1 mg, 0.06 mmol), acceptor 4a (11.6 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5ba (40 mg, 99%).

[0181] The donor 1b (92.2 mg, 0.12 mmol), the acceptor 4a (23.2 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted for 8 h according to process A to obtain 5ba (60 mg, 74%).

[0182] 5ba is a white solid: [α] D 25 = +24.0 (c 1.1, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.06-8.01(m,2H),7.94-7.89(m,2H),7.86-7.78(m,4H),7.60-7.55(m,1H),7.55-7.49(m,2H),7.46- 7.41(m,4H),7.39-7.32(m,4H),7.30-7.27(m,2H),7.20-7.13(m,2H),6.59-6.53(m,2H),6.29(d,J=9.4Hz,1H,H-1'),6.06 (t,J=9.7Hz,1H),5.86(d,J=8.2Hz,1H,H-5),5.76(t,J=9.8Hz,1H),5.63(t,J=9.5Hz,1H),4.97(d,J=13.8Hz,1H),4.83(d, J=13.9Hz,1H),4.65(dd,J=12.5,2.8Hz,1H),4.48(dd,J=12.5,5.0Hz,1H),4.36(ddd,J=10.1,4.9,2.7Hz,1H),3.70(s,3H); 13C NMR (100MHz, CDCl3) δ166.1,165.6,165.3,162.0,159.0,151.2(C-2),137.0(C-6),133.9,133.8,133.6,133.45,130.1(2C),130.0,129.9,129. 8,129.5,128.6(2C),128.55,128.5(2C),128.0,113.7,103.7(C-5),81.5(C-1'),75.5,73.0,70.5,69.0,62.7,55.2,44.1.HRMS(ESI)m / zcalcd for C 46 H 38 N2O 12 Na[M+Na] + :833.2317; found:833.2335.

[0183] Application Example 21

[0184]

[0185] The donor 1b (46.1 mg, 0.06 mmol), the acceptor 4d (15.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5bd (31 mg, 73%), which was a white solid: [α] D 25 = +23.0 (c 1.65, CHCl3); 1 H NMR (400MHz, CDCl3) δ8.12-7.98(m,2H),7.96-7.90(m,2H),7.90-7.83(m,2H),7.83-7. 75(m,3H),7.63-7.22(m,12H),7.17(d,J=7.7Hz,1H,H-5),6.52(d,J=9.5Hz,1H,H-1'),6 .10(t,J=9.6Hz,1H),5.77(t,J=9.7Hz,1H),5.69(t,J=9.5Hz,1H),4.63(dd,J=12.3,2.4 Hz,1H),4.48(dd,J=12.4,5.1Hz,1H),4.41(ddd,J=10.4,5.1,2.5Hz,1H),1.49(s,18H); 13CNMR(100MHz, CDCl3)δ166.2,165.55,165.5,165.3,162.8,154.1(C-2),149.3,143.2(C-6),133.8,133.5,133.4,130.2,130.0,129.9, 129.8,129.5,128.7,128.6(2C),128.55,128.5,128.1,97.5(C-5),85.2,81.5(C-1'),75.6,73.3,70.8,69.1,62.8,27.7.HRMS(ESI)m / z calcd for C 48 H 48 N3O 14 [M+H] + :890.3131; found:890.3150.

[0186] Application Example 22

[0187]

[0188] The donor 1c (43.6 mg, 0.06 mmol), the acceptor 4a (11.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5ca (31 mg, 81%), which was a white solid: [α] D 25 = +28.7 (c 1.0, CHCl3); 1 H NMR (400MHz, CDCl3) δ7.94-7.83(m,2H),7.58(t,J=7.5Hz,1H),7.43-7.29(m,11H),7 .22-7.07(m,9H),6.59-6.44(m,2H),5.94(d,J=9.4Hz,1H,H-1'),5.83(d,J=8.2Hz,1 H,H-5),5.34(t,J=9.3Hz,1H),4.94(d,J=13.8Hz,1H),4.89-4.73(m,3H),4.70-4.49 (m,4H),3.97(t,J=9.1Hz,1H),3.87(t,J=9.1Hz,1H),3.80-3.72(m,3H),3.71(s,3H); 13C NMR(100MHz, CDCl3))δ165.3,162.1,158.9,151.25(C-2),137.8(C-6),137.7,137.6,137.5,133.6,130.0,128.8,128.7,128.6(2C),128.4, 128.1(2C),128.0(2C),127.9,127.85,113.7,103.2(C-5),82.8,81.4(C-1'),75.6,75.4,73.6,72.3,68.3,55.2,55.2,43.9.HRMS(ESI)m / z calcd for C 46 H 44 N2O9Na[M+Na] + :791.2939; found:791.2955.

[0189] Application Example 23

[0190]

[0191] Donor 1d (46.1 mg, 0.06 mmol), acceptor 4d (15.6 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5dd (41 mg, 93%).

[0192] Donor 1d (92.2 mg, 0.12 mmol), acceptor 4d (31.2 mg, 0.1 mmol) and catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 8 h according to process A to obtain 5dd (76.5 mg, 86%).

[0193] 5dd is a white solid: [α] D 25 = +88.2 (c 2.05, CHCl3); 1H NMR (400MHz, CDCl3) δ8.05 (dd, J = 8.1, 1.4Hz, 2H), 8.02-7.96 (m, 2H), 7.93-7.84 (m, 3H), 7. 80-7.73(m,2H),7.70-7.63(m,1H),7.58-7.50(m,3H),7.49-7.39(m,4H),7.36-7.29(m,2H ),7.29-7.20(m,3H),6.51(d,J=9.4Hz,1H,H-1'),6.10(d,J=3.2Hz,1H),5.95(t,J=9.7Hz, 1H),5.82(dd,J=10.1,3.2Hz,1H),4.59(d,J=6.8Hz,2H),4.51-4.35(m,1H),1.50(s,18H); 13 C NMR (100MHz, CDCl3) δ166.1,165.7,165.4(2C),162.8,154.1,149.3,143.3,134.0,133.8,133.5,133.5,130.2,130.0,129.9(2C) ,129.3,129.05,129.0,128.7,128.6,128.5,128.3,97.6,85.2,81.7(C-1'),74.75,72.1,68.7,68.45,62.3,27.75.HRMS(ESI)m / z calcd for C 48 H 48 N3O 14 [M+H] + :890.3131; found:890.3134.

[0194] Application Example 24

[0195]

[0196] The donor 1e (46.1 mg, 0.06 mmol), the acceptor 4d (15.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5ed (41 mg, 92%), which was a white solid: [α] D 25 = +62.8 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ8.20-8.11(m,2H),8.11-8.04(m,2H),8.04-7.98(m,2H),7.91-7.83(m,2H),7.81(d,J= 7.7Hz,1H),7.69-7.58(m,2H),7.57-7.46(m,6H),7.40(dd,J=8.4,7.2Hz,2H),7.36-7.29(m,2H),7.14(d,J= 7.7Hz,1H),6.78(d,J=9.1Hz,1H,H-1'),6.11(t,J=3.5Hz,1H),5.97(dd,J=9.0,3.3Hz,1H),5.67(dd,J=3.8, 2.3Hz,1H),5.04-4.93(m,1H),4.89(ddd,J=7.5,5.0,2.2Hz,1H),4.81(dd,J=11.4,5.1Hz,1H),1.51(s,18H); 13 C NMR (100MHz, CDCl3) δ166.1,165.3,165.1,162.7,154.3,149.4,144.0,134.0,133.75,133.35,130.1,130.0,129.95,129.5,129.15, 129.0,128.9,128.9,128.7,128.6,128.5(2C),128.3,97.2,85.2,77.9(C-1'),76.1,69.55,69.0,68.05,61.3,27.75.HRMS(ESI)m / z calcd for C 48 H 48 N3O 14 [M+H] + :890.3131; found:890.3129.

[0197] Application Example 25

[0198]

[0199] The donor 1f (77.8 mg, 0.12 mmol), the acceptor 4a (23.2 mg, 0.1 mmol) and the catalyst PPh3AuNTf2 (1.8 mg, 0.0024 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 8 h according to process A to obtain 5fa (58 mg, 84%) as a white solid: [α] D 25 = -20.0 (c 1.75, CHCl3); 1H NMR (400MHz, CDCl3) δ8.23-8.04(m,4H),7.87-7.75(m,2H),7.74-7.61(m,2H),7.59-7.43(m,6H),7 .38-7.28(m,2H),7.24-7.15(m,2H),6.71(d,J=9.6Hz,1H,H-1'),6.67-6.48(m,2H),6.00(td,J=3.5 ,1.1Hz,1H),5.86(d,J=8.2Hz,1H),5.71(dd,J=9.6,3.6Hz,1H),5.32(dd,J=3.4,1.2Hz,1H),5.02( d,J=13.8Hz,1H),4.89(d,J=13.9Hz,1H),4.58(q,J=7.3Hz,1H),3.71(s,3H),1.76(d,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ165.2,165.15,165.1,162.2,159.0,151.5,137.4,134.0,133.8,130.05,130.0(2C),129.9,129.1,1 29.0,128.95,128.9,128.7(2C),128.5,113.8,103.3,74.6(C-1'),74.5,72.1,69.8,67.6,55.3,44.0,16.2.HRMS(ESI)m / z calcdfor C 39 H 35 N2O 10 [M+H] + :691.2286; found:691.2256.

[0200] Application Example 26

[0201]

[0202] The donor 1g (38.1 mg, 0.06 mmol), the acceptor 4d (15.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5gd (32 mg, 85%), which was a white solid: [α] D 25 = +122.8 (c 0.85, CHCl3); 1H NMR (400MHz, CDCl3) δ8.14-8.07(m,2H),7.92-7.87(m,2H),7.87-7.81(m,3H),7. 68-7.63(m,1H),7.57-7.42(m,4H),7.37-7.27(m,4H),7.18(d,J=7.7Hz,1H),6.3 6(d,J=9.4Hz,1H),5.97(t,J=9.7Hz,1H),5.80(d,J=3.4Hz,1H),5.74(dd,J=10.0 ,3.3Hz,1H),4.41(dd,J=13.5,1.9Hz,1H),4.14(d,J=13.4Hz,1H),1.49(s,18H); 13 C NMR (100MHz, CDCl3) δ165.8,165.6,165.45,162.7,154.2,149.35,143.3,133.8(2C),133.6,130.2,130.0,12 9.9,129.5,128.9,128.8,128.6,128.5,128.4,97.5,85.2,82.2,72.0,69.4,68.85,67.7,27.8.HRMS(ESI)m / z calcd forC 40 H 42 N3O 12 [M+H] + :756.2763; found:756.2769.

[0203] Application Example 27

[0204]

[0205] The donor 1i (38.1 mg, 0.06 mmol), the acceptor 4a (11.6 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process A for 1 h to obtain 5ia (34 mg, 99%), which was a white solid: [α] D 25 = -18.9 (c 1.0, CHCl3); 1H NMR (400MHz, CDCl3) δ8.18-8.04(m,2H),8.04-7.86(m,4H),7.65-7.52(m,3H),7.48(t ,J=7.7Hz,2H),7.44-7.33(m,7H),6.82-6.70(m,2H),6.35(d,J=5.3Hz,1H),5.92(dd,J =5.9,4.6Hz,1H),5.74(t,J=5.6Hz,1H),5.67(d,J=8.1Hz,1H),5.07(d,J=13.7Hz,1H) ,4.95(d,J=13.7Hz,1H),4.83(dd,J=12.1,2.7Hz,1H),4.75-4.59(m,2H),3.74(s,3H); 13 C NMR (100MHz, CDCl3) δ166.1,165.4,165.3,162.2,159.15,151.0,137.45,133.9,133.8,130.7,130.0,129.9,129.7,1 29.3,128.9,128.8,128.7(2C),128.6,128.5,113.8,103.2,88.9,80.5,74.05,71.2,63.7,55.3,43.9.HRMS(ESI)m / z calcd for C 38 H 36 N3O 10 [M+NH4] + :694.2395; found:694.2397.

[0206] Application Example 28

[0207]

[0208] Donor 1b (46.1 mg, 0.06 mmol), acceptor 4e (6.3 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (hexafluoroisopropanol, 0.5 mL) and reacted according to process B for 1 h to obtain 7be (22.5 mg, 64%), which is a known compound.

[0209] Donor 1b (46.1 mg, 0.06 mmol), acceptor 4f (6.5 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to procedure B for 1 h to obtain 7bf (29 mg, 82%), which is a known compound.

[0210] Donor 1b (76.9 mg, 0.1 mmol), acceptor 4f (26.0 mg, 0.2 mmol), BSTFA (106 μL, 0.4 mmol) and catalyst PPh3AuNTf2 (1.5 mg, 0.02 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 48 h according to process C to obtain 7bf (70 mg, 99%).

[0211] The donor 1b (46.1 mg, 0.06 mmol), the acceptor 4g (11.9 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to the process B for 1 h to obtain 7bg (28 mg, 68%), which was a white solid. [α] D 25 = -21.1 (c 0.45, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.36(s,1H),8.07-8.01(m,2H),7.96-7.89(m,3H),7.89-7.84(m,2H),7 .83-7.77(m,2H),7.63-7.47(m,3H),7.47-7.40(m,3H),7.40-7.31(m,4H),7.31-7.27(m,2H) ,6.20(d,J=9.3Hz,1H),6.09(t,J=9.6Hz,1H),5.78(t,J=9.8Hz,1H),5.62(t,J=9.5Hz,1H),4 .67(dd,J=12.5,2.7Hz,1H), 4.50(dd,J=12.5,5.1Hz,1H), 4.40(ddd,J=10.1,5.0,2.8Hz,1H). 13CNMR (100MHz, CDCl3) δ165.2,164.6,164.4,164.3,158.1,148.8,142.8,133.1,132.9,132.7,132.5,129.2,129.0 5,129.0,128.9,128.4,127.7,127.7(2C),127.5,126.9,80.0,74.7,71.2,69.7,68.95,67.8,61.65.HRMS(ESI)m / z calcd for C 38 H 30 IN2O 11 [M+H] + :817.0889; found:817.0865.

[0212] Donor 1b (38.5 mg, 0.05 mmol), acceptor 4g (23.7 mg, 0.1 mmol), BSTFA (53 μL, 0.2 mmol) and catalyst PPh3AuNTf2 (7.4 mg, 0.01 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process C for 1 h to obtain 7bg (38 mg, 93%).

[0213] Application Example 29

[0214]

[0215] The donor 1f (38.9 mg, 0.06 mmol), the acceptor 4e (6.3 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to process B for 1 h to obtain 7fe (25 mg, 92%), 7fe as a white solid. [α] D 25 = -29.3 (c 1.3, CHCl3); 1H NMR(400MHz, CDCl3)δ8.71(s,1H),8.20-8.12(m,2H),8.13-8.05(m,2H),7.87-7 .79(m,2H),7.72-7.59(m,2H),7.59-7.45(m,5H),7.36-7.27(m,3H),6.67(d,J=9 .5Hz,1H,H-1'),6.03(td,J=3.5,1.1Hz,1H),5.75(dd,J=9.5,3.6Hz,1H),5.32( dd,J=3.5,1.4Hz,1H),4.59(q,J=7.3Hz,1H),1.94(s,3H),1.74(d,J=7.3Hz,3H); 13 C NMR (100MHz, CDCl3) δ165.3,165.2,163.4,150.6,135.1,134.0,133.9,130.1,130.0,129.2,129.0, 128.95,128.9,128.7,128.45,112.0,74.6(C-1'),74.0,72.2,69.9,67.4,16.2,12.8.HRMS(ESI)m / z calcd for C 32 H 29 N2O9[M+H] + :585.1868; found:585.1862.

[0216] The donor 1f (32.5 mg, 0.05 mmol), the acceptor 4e (12.6 mg, 0.1 mmol), BSTFA (53 μL, 0.2 mmol) and the catalyst PPh3AuNTf2 (7.4 mg, 0.01 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process C for 1 h to obtain 7fe (26 mg, 89%).

[0217] The donor 1f (38 mg, 0.06 mmol), the acceptor 4f (6.5 mg, 0.05 mmol) and the catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to the procedure B for 1 h to obtain 7ff (25 mg, 86%), which was a white solid. [α] D 25 = -51.9 (c 0.3, CHCl3); 1H NMR (400MHz, CDCl3) δ8.80 (d, J = 4.8Hz, 1H), 8.16-8.12 (m, 2H), 8.11-8.06 (m, 2H ),7.85-7.79(m,2H),7.69-7.63(m,2H),7.60-7.47(m,6H),7.34-7.28(m,2H),6 .62(dd,J=9.5,1.6Hz,1H,H-1'),6.00(td,J=3.5,1.1Hz,1H),5.68(dd,J=9.5,3 .6Hz,1H),5.33(dd,J=3.4,1.3Hz,1H),4.70-4.45(m,1H),1.74(d,J=7.3Hz,3H). 13 C NMR (100MHz, CDCl3) δ165.2,165.1,156.55,156.3,149.1,142.1,139.7,134.1,134.0,130.1,130.0(2C),129 .1,129.0(2C),128.9,128.7,128.3,124.1,123.7,74.8(C-1'),74.55,71.9,69.8,67.4,16.2.HRMS(ESI)m / z calcd forC 31 H 26 FN2O9[M+H] + :589.1617; found:589.1618.

[0218] Donor 1f (32.5 mg, 0.05 mmol), acceptor 4f (13 mg, 0.1 mmol), BSTFA (53 μL, 0.2 mmol) and catalyst PPh3AuNTf2 (7.4 mg, 0.01 mmol) were dissolved in dry CH2Cl2 (2 mL) and reacted according to process C for 1 h to obtain 7ff (23 mg, 79%).

[0219]

[0220] Donor 1i (38.1 mg, 0.06 mmol), acceptor 4e (6.3 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to process B for 1 h to obtain 7ie (24 mg, 84%), which is a known compound.

[0221] Donor 1i (63.5 mg, 0.1 mmol), acceptor 4e (25.2 mg, 0.2 mmol), BSTFA (106 μL, 0.4 mmol) and catalyst PPh3AuNTf2 (1.5 mg, 0.002 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 48 h according to process C to obtain 7ie (56.4 mg, 99%).

[0222] The donor 1i (2.59 g, 4.08 mmol), the acceptor 4f (442 mg, 3.40 mmol) and the catalyst PPh3AuNTf2 (120 mg, 0.16 mmol) were dissolved in dry CH2Cl2 (20 mL) and HFIP (5 mL) and reacted according to process B for 1 h to obtain 7if (1.50 g, 64%). 7if (200 mg, 0.35 mmol) was dissolved in a mixed solvent of MeOH and THF (6 mL, v / v = 2:1), K2CO3 (174 mg, 1.26 mmol) was added, stirred for 4 h, and a cationic resin (Amberlite IR120, Na-form) was used to adjust the pH to about 7, filtered and concentrated by rotary evaporation, and purified by silica gel column (DCM / MeOH=10:1) to obtain the known compound 7if' (39.4 mg, 71%). (7if' is the product of complete removal of benzoyl groups, i.e. 5-F uridine, which is a very important prodrug of nucleoside drugs. Watanabe, KA; Halat, MMJ; Hollenberg, DH; Nisselbaum, JS; Fox, JJ Nucleosides. 114. 5'-O-Glucuronides of 5-fluorouridine and 5-fluorocytidine. Masked precursors of anticancer nucleosides. J. Med. Chem. 1981, 24, 893-897.)

[0223] Donor 1i (63.5 mg, 0.1 mmol), acceptor 4f (26 mg, 0.2 mmol), BSTFA (106 μL, 0.4 mmol) and catalyst PPh3AuNTf2 (1.5 mg, 0.002 mmol) were dissolved in dry CH2Cl2 (4 mL) and reacted for 48 h according to process C to obtain 7if (56.9 mg, 99%).

[0224] Donor 1i (38 mg, 0.06 mmol), acceptor 4h (9 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were dissolved in dry CH2Cl2 (2 mL) and HFIP (0.5 mL) and reacted according to process B for 1 h to obtain white solid 7ih (22.2 mg, 71%), 7ih is a known compound.

[0225] Application Example 30

[0226]

[0227] Donor 1j (38.1 mg, 0.06 mmol), acceptor 4e (6.3 mg, 0.05 mmol) and catalyst PPh3AuNTf2 (8.8 mg, 0.012 mmol) were added to dry CH2Cl2 (2 mL) and HFIP (0.5 mL) to give 7je (23 mg, 81%) according to procedure B. [α] D 25 = +22.4 (c 0.6, CHCl3); 1 H NMR(400MHz, CDCl3)δ8.97(s,1H),8.13-8.06(m,2H),8.06-7.98(m,4H),7.6 5-7.51(m,3H),7.50-7.35(m,6H),7.29(d,J=1.4Hz,1H),6.28(d,J=3.2Hz,1H ,H-1'),5.94(t,J=3.0Hz,1H),5.76(t,J=3.0Hz,1H),5.07-4.89(m,1H),4.75 (dd,J=11.9,5.9Hz,1H),4.67(dd,J=11.9,4.7Hz,1H),1.92(d,J=1.1Hz,3H). 13 CNMR (100MHz, CDCl3) δ166.25,165.4,165.35,163.8,150.3,136.05,134.1,134.05,133.5,130.2,12 9.95,129.5,128.8(2C),128.6(2C),128.5,111.4,91.2,83.6,80.6,77.6,63.9,12.7.HRMS(ESI)m / z calcd for C 31 H 26 N2O9Na[M+Na] + :593.1530; found:593.1532.

[0228] 7jf (18.4 mg, 64%) was obtained by replacing 4e with 4f as a white solid. D 25 = +41.0 (c 0.8, CHCl3); 1 HNMR(400MHz, CDCl3)δ9.05(d,J=4.7Hz,1H),8.12-8.06(m,2H),8.06-7.98(m,4H),7.66-7.51(m,4H),7.50-7.37(m,6H),6.27(dd,J=3.1,1.0Hz ,1H),5.88(t,J=2.9Hz,1H),5.76(t,J=2.9Hz,1H),4.97(ddd,J=5.9,4.6,3.1Hz,1H),4.78(dd,J=11.9,5.9Hz,1H),4.66(dd,J=12.0,4.6Hz,1H); 13 C NMR (150MHz, CDCl3) δ166.2,165.4,165.3,156.8,156.6,148.7,141.6,140.0,134.25,134.2,133.6,130.2,12 9.95,129.9,129.4,128.9,128.8,128.65,128.4,128.3,124.55,124.3,91.3,84.0,80.6,63.9.HRMS(ESI)m / z calcd forC 30 H 23 FN2O9Na[M+Na] + :597.1280; found:597.1287.

[0229] Application Example 31

[0230]

[0231] The donor 1n (1.1 g, 2.0 mmol), the acceptor 2b (590 mg, 1.67 mmol) and the catalyst PPh3AuNTf2 (29.6 mg, 0.04 mmol) were dissolved in dry CH2Cl2 (30 mL) and 3nb (910 mg, 83%) was prepared according to process A. 3nb was a white foamy solid: [α] D 25 = -111.1 (c 1.0, CHCl3); 1H NMR(400MHz, CDCl3)δ8.33(s,1H),8.32(s,1H),8.06-7.94(m,2H),7.94- 7.83(m,2H),7.63-7.56(m,1H),7.56-7.50(m,1H),7.45-7.38(m,2H),7. 38-7.31(m,2H),6.50(d,J=6.5Hz,1H),6.02(t,J=6.2Hz,1H),5.93(dd,J =6.1,3.4Hz,1H),4.76(q,J=3.6Hz,1H),4.17-3.94(m,2H),1.55(s,9H); 13 C NMR (100MHz, CDCl3) δ165.5, 165.1, 158.9 (d, J = 209.1Hz), 152.8 (d, J = 17.8Hz), 152.0 (d, J = 19.6Hz), 149.2, 140.8 (d, J = 3.0Hz), 13 4.05,130.0,129.9,128.8,128.7,128.6,128.15,120.3(d,J=4.5Hz),85.9,83.1,83.0,77.4,74.5,72.4,44.5,28.2.HRMS(ESI)m / z calcd forC 29 H 28 ClFN5O7[M+H] + :612.1659; found:612.1664.

[0232] 3nb (100 mg, 0.163 mmol) was dissolved in dichloromethane (6.5 mL), TFA (250 μL, 3.3 mmol) was added at room temperature, and the reaction was stirred for 8 h. NaHCO3 was added to quench the reaction. After filtration, the product was concentrated by rotary evaporation and purified by silica gel column (CH2Cl2 / CH3OH=50:1) to give 6-NH2-intermediate (71 mg, 85%) as a white solid. The product was directly transferred to the next step without further treatment.

[0233] The above intermediate (71 mg, 0.139 mmol) was dissolved in THF / MeOH (4.5 mL, V / V=1:2), K2CO3 (77 mg, 0.56 mmol) was added, and the reaction was stirred for 8 h. A cationic resin (Amberlite IR120, Na-form) was added to quench the reaction. After filtration, the mixture was concentrated by rotary evaporation and purified by silica gel column (CH2Cl2 / CH3OH=5:1) to obtain a white solid 3nb' (37 mg, 88%). (3nb' can significantly inhibit RNA adenosine deaminase 1 (ADAR1) and can be used to prevent and / or treat cancer or tumor-related diseases caused by abnormal activity of this enzyme, especially prostate cancer, leukemia, colon cancer, etc., see Chinese patent CN113549076A for details).

Claims

1. A tert-butylethynylthiophenol ether sugar donor, characterized in that: The structure of the donor is as follows: Gly is any of the following structures: PG is one or more hydroxyl protecting groups, glycosyl groups or sugar chains.

2. The tert-butylethynylthiophenol ether saccharide donor according to claim 1, characterized in that Specifically, the compound has the following structure: R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, Bn is benzyl, and X is Cl, Br or I.

3. The method for preparing the tert-butylethynylthiophenol ether sugar donor according to claim 2, characterized in that: The synthetic route is as follows: R is R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, Bn is benzyl, and X is Cl, Br or I; The specific preparation process is as follows: the compound shown in formula I and 3,3-dimethyl-1-butyne undergo Sonogashira reaction to obtain the compound shown in formula III.

4. The preparation method according to claim 3, characterized in that: The Sonogashira reaction comprises the following steps: dissolving compound I, Ph3P, Pd(PPh3)2Cl2 and CuI in an organic solvent, cooling to -78°C to -40°C in an inert gas atmosphere, adding 3,3-dimethyl-1-butyne, heating to 50 to 100°C, and reacting until TLC shows that the reaction is complete, wherein the first organic solvent is selected from one or more of N,N-dimethylformamide, diisopropanolamine, tetrahydrofuran, dichloromethane, toluene and acetone.

5. The preparation method according to claim 4, characterized in that: The molar ratio of the compound shown in formula I, 3,3-dimethyl-1-butyne, (PPh3)2PdCl2, CuI and PPh3 is 1:(2.5-3.5):(0.08-0.12):(0.3-0.5)(0.3-0.5); the organic solvent is a mixed solvent of N,N-dimethylformamide and diisopropanolamine, and the volume ratio of N,N-dimethylformamide and diisopropanolamine is 1:(1-3).

6. Use of the tert-butylethynylthiophenol ether glycosyl donor according to claim 1 or 2 in nucleoside synthesis, characterized in that: The synthetic route is as follows: R is R1 and R2 are each independently selected from H, Ac, Bz or Bn, Ac is acetyl, Bz is benzoyl, and Bn is benzyl; R3 is H, F or Cl, R4 is Cl, Br or I, R5 is H, F, I, CH3, CF3 or CH3CH2, and X is Cl, Br or I; The specific synthesis process is as follows: Method A: dissolving the donor represented by formula III and the acceptor represented by formula IV in an organic solvent, and obtaining the nucleoside compound represented by formula V in the presence of a desiccant and under the action of a catalyst; Method B: dissolving the donor represented by formula III and the acceptor represented by formula IV in an organic solvent and obtaining the nucleoside compound represented by formula V under the action of a desiccant, a promoter and a catalyst; The catalyst is a monovalent gold complex, and the promoter is BSTFA, NIS or TMSOT.

7. The use according to claim 6, characterized in that: In method A, the molar ratio of the donor shown in formula III and the acceptor shown in formula IV is (1.3-1.1):1, and the molar ratio of the donor shown in formula III and the catalyst is 1:(0.02-0.2); the concentration of the donor in the organic solvent is 30-60 mM.

8. The use according to claim 6, characterized in that: Method A also includes adding hexafluoroisopropanol into the organic solvent, the volume ratio of the organic solvent to the hexafluoroisopropanol is (3-5):1, and the concentration of the donor in the organic solvent and the hexafluoroisopropanol is 20-170 mM.

9. The use according to claim 6, characterized in that: In method B, the molar ratio of the donor represented by formula III, the acceptor represented by formula IV, the promoter and the catalyst is 1:(1-2):(4-8):(0.02-0.2); the concentration of the donor in the organic solvent is 20-100 mM.

10. The use according to any one of claims 6 to 9, characterized in that: The desiccant is a molecular sieve, and the added amount of the molecular sieve is 0.3-0.8 g / mmol based on the receptor.

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