Preparation method of C-acyl glycoside compound

Abstract

The invention discloses a preparation method of a C-acyl glycoside compound, which comprises the following steps: by taking aromatic aldehyde as a raw material and glucoside as an alkyl source, simultaneously adding a catalyst, a ligand, a hydrogen transfer reagent, alkali and a solvent into a reaction bottle, and carrying out coupling reaction in a nitrogen atmosphere to obtain the C-acyl glycoside compound. The method provided by the invention has the advantages of cheap and easily available raw materials, simple experiment, and excellent substrate adaptability, functional group compatibility and reaction selectivity; the product yield is high, the influence on the environment is small, and an efficient, economical and environment-friendly synthesis strategy is provided for the development of the pharmaceutical chemical industry field.

Description

Technical Field

[0001] The invention belongs to the technical field of pharmaceutical chemical intermediate synthesis, and specifically relates to a method for preparing a C-acyl glycoside compound. Background Art

[0002] Glycosides are a class of organic compounds that are widely present in nature. They are composed of a sugar group and a non-sugar group connected by a glycosidic bond. They have rich and diverse biological activities and show important application value in many fields. For example, in the field of medicine, many natural glycosides have antibacterial, anti-inflammatory, antiviral, anti-tumor and other pharmacological activities, providing a rich resource of lead compounds for drug research and development; in the cosmetics industry, glycoside compounds are widely used in various skin care products because of their good moisturizing, anti-oxidation, anti-aging and other effects. They can improve the texture and appearance of the skin and meet people's pursuit of beauty.

[0003] C-acyl glycosides are a special type of glycoside compounds. Their characteristic is that the acyl substituent is directly connected to a specific position of the sugar ring, usually C-1 or other unconventional positions, which is in sharp contrast to the classic O-glycosides (glycosidic bonds are connected to oxygen atoms). This unique structure gives C-acyl glycosides some special chemical properties and biological activities. Due to the introduction of acyl groups, the electron cloud distribution and spatial conformation of glycoside molecules are changed, which may cause unique interaction patterns with receptors or targets in the body, thereby showing different physiological effects. For example, some C-acyl glycosides have been found to have inhibitory effects on specific enzymes or can regulate cell signal transduction pathways, which brings new opportunities for them in the field of drug discovery and development and can be widely used as pharmaceutical and chemical intermediates.

[0004] Chemical synthesis and biosynthesis are common methods for synthesizing C-acylglycosides, but these methods have their own limitations. For example, although certain reactions mediated by metal organic compounds can achieve the synthesis of C-acylglycosides, the reaction conditions are harsh, expensive metal catalysts and ligands are required, and the atom economy of the reaction is low. In addition, these methods still need to be further improved in terms of the scope of application of substrates and the selectivity of products, and it is difficult to use them as a general and efficient synthetic strategy in actual production. The article Catalytic Multicomponent Synthesis of C-AcylGlycosides by Consecutive Cross-Electrophile Couplings discloses a method for synthesizing C-acylglycosides by catalytic multicomponents through continuous cross-electrophile coupling, which is only applicable to pre-prepared halogenated glycoside substrates and has certain limitations.

[0005] Therefore, developing a simple, efficient, highly selective and environmentally friendly method for synthesizing C-acylglycosides has important theoretical significance and practical application value. Summary of the invention

[0006] In view of the above problems existing in the prior art, the object of the present invention is to provide a simple and efficient method for synthesizing C-acyl glycosides, so as to provide more powerful support for the research and application of C-acyl glycoside compounds.

[0007] The present invention adopts the following technical solution: A method for preparing a C-acyl glycoside compound, specifically comprising: Using aromatic aldehyde 1 as raw material and glycoside 2 as alkyl source, a catalyst, a ligand, a hydrogen transfer reagent, a base, and a solvent were added to the reaction bottle at the same time, and a coupling reaction was carried out in a nitrogen atmosphere to obtain a pharmaceutical chemical intermediate C-acyl glycoside compound 3. The synthetic route is as follows: Wherein, R is an aryl or heteroaryl group; the glycoside is a furanose or a pyranose, wherein PG can be a protecting group such as a methyl group, an acetyl group, a pivaloyl group or a phenylacetyl group.

[0008] Preferably, the catalyst is a copper salt, which is one of CuCl, CuI, Cu(acac)2, CuPO2Ph2, Cu2SO4, Cu2S, Cu(NO3)2, and CuCl2; more preferably, the catalyst is CuPO2Ph2.

[0009] Preferably, the ligand is a nitrogen ligand or a phosphorus ligand, wherein the nitrogen ligand is one of 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-4,4'-dimethyl, 2,2'-bipyridine-4,4'-di-tert-butyl, 2,2'-bipyridine-4,4'-dimethoxy, 1,10-phenanthroline, and 2,9-dimethyl-1,10-phenanthroline; the phosphorus ligand is one of 1,2-bis(diphenylphosphino)ethane and 1,2-bis(dimethylphosphino)ethane; more preferably, the ligand is 2,2'-bipyridine-4,4'-dimethoxy.

[0010] Preferably, the hydrogen transfer agent is one of di-tert-butyl peroxide, dibenzoyl peroxide, di-tert-amyl peroxide, tert-butyl peroxybenzoate, and tert-butyl hydroperoxide; more preferably, the hydrogen transfer agent is di-tert-butyl peroxide.

[0011] Preferably, the base is an organic base or an inorganic base, wherein the organic base is one of 4-dimethylaminopyridine, N,N-diisopropylethylamine, triethylamine, and triethylenediamine; the inorganic base is one of Na2CO3, Cs2CO3, K2CO3, Li2CO3, and K2PO4; more preferably, the base is triethylenediamine.

[0012] Preferably, the solvent is one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, n-hexane and cyclohexane; more preferably, the solvent is cyclohexane.

[0013] Preferably, the molar ratio of the aromatic aldehyde 1, glycoside 2, metal catalyst, ligand, hydrogen source and base is 1-3:1-3:0.05-0.2:0.05-0.3:1-10:1-10; more preferably, the molar ratio is 2:1:0.1:0.15:4:3.5.

[0014] Preferably, the molar volume ratio of the aromatic aldehyde 1 to the solvent is 0.4 mmol:1-10 mL.

[0015] Preferably, the reaction temperature is 50 to 120°C, more preferably 90°C.

[0016] Preferably, the reaction time is 1 to 24 hours, more preferably 12 hours.

[0017] The beneficial effects of the present invention are: The present invention provides a method for synthesizing C-acyl glycoside compounds with high selectivity and high yield through a cross-coupling reaction. The process is simple and easy to operate; it is environmentally friendly and in line with the concept of green chemistry; the applicable substrate range is very wide, the functional group compatibility is strong, and it can adapt to a variety of different types of substrates to participate in the reaction, and the raw materials are cheap and easily available.

[0018] In summary, the present invention provides new ideas and methods for in-depth exploration of related fields, and also shows good application prospects in practical applications. The obtained products can be used as pharmaceutical and chemical intermediates and play an important role in multiple fields such as drug synthesis and material science. DETAILED DESCRIPTION

[0019] The present invention is further described below.

[0020] As described above, the present invention discloses a method for preparing a C-acyl glycoside compound, comprising the following steps: adding an aromatic aldehyde 1, a glycoside 2, a catalyst, a ligand, a hydrogen transfer reagent and a base in a molar ratio of 1 to 3: 1 to 3: 0.05 to 0.2: 0.05 to 0.3: 1 to 10: 1 to 10 into a reaction bottle, and then adding a solvent, and performing a coupling reaction in a nitrogen atmosphere at 50 to 120° C. for 1 to 24 hours to obtain a C-acyl glycoside 3; wherein the volume molar ratio of the solvent to the aromatic aldehyde 1 is 1 to 10 mL: 0.4 mmol.

[0021] Wherein, the catalyst is selected from one of CuCl, CuI, Cu(acac)2, CuPO2Ph2, Cu2SO4, Cu2S, Cu(NO3)2, and CuCl2.

[0022] The ligand is a nitrogen ligand or a phosphorus ligand; the nitrogen ligand is 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-4,4'-dimethyl, 2,2'-bipyridine-4,4'-di-tert-butyl, 2,2'-bipyridine-4,4'-dimethoxy, 1,10-phenanthroline, 2,9-dimethyl-1,10-phenanthroline; the phosphorus ligand is one of 1,2-bis(diphenylphosphino)ethane and 1,2-bis(dimethylphosphino)ethane.

[0023] The hydrogen transfer agent is one of di-tert-butyl peroxide, dibenzoyl peroxide, di-tert-amyl peroxide, tert-butyl peroxybenzoate and tert-butyl hydroperoxide.

[0024] The base is an organic base or an inorganic base; the organic base is one of 4-dimethylaminopyridine, N,N-diisopropylethylamine, triethylamine, and triethylenediamine; the inorganic base is one of Na2CO3, Cs2CO3, K2CO3, Li2CO3, and K2PO4.

[0025] The solvent is one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, n-hexane and cyclohexane.

[0026] The present invention will be further described below in conjunction with specific examples. It should be understood that these examples are only used to illustrate the present invention and are not intended to limit the scope of the present invention.

[0027] Embodiment 1: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3a (39.4 mg, 0.128 mmol, yield 64%). 1 H NMR (400 MHz, CDCl3) δ8.06 (d, J = 8.5 Hz, 2H), 7.56 (t, J = 7.4 Hz, 1H),7.44 (t, J = 7.7 Hz, 2H), 5.01 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 6.0Hz, 1H), 4.53 (t, J = 6.4 Hz, 1H), 4.39 – 4.30 (m, 2H), 3.33 (s, 3H), 1.49 (s, 3H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.1, 132.2, 128.7, 127.4, 111.6,108.4, 84.2, 83.3, 80.9, 64.1, 53.9, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcdfor C 16 H 21 O6: 309.1333. Found: 309.1331. Embodiment 2: Aromatic aldehyde 1b (48.0 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3b (40.6 mg, 0.126 mmol, yield 63%). 1 H NMR (400 MHz, CDCl3) δ 7.87 (d, J = 9.1 Hz, 2H), 7.40 – 7.30 (m, 2H), 5.02 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.53 (t, J = 6.9Hz, 1H), 4.39 – 4.30 (m, 2H), 3.34 (s, 3H), 2.40 (s, 3H), 1.50 (s, 3H), 1.34(s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.3, 137.2, 132.9, 129.2, 128.6, 127.3,125.9, 111.6, 108.4, 84.2, 83.3, 80.9, 64.0, 53.9, 25.4, 24.0, 20.3.HRMS(ESI)m / z ([M+H] + ) calcd for C 17 H 23 O6: 323.1489. Found: 323.1489. Embodiment 3: Aromatic aldehyde 1c (53.6 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3c (45.7 mg, 0.136 mmol, yield 68%). 1 H NMR (400 MHz, CDCl3) δ 7.99 (d, J = 8.4 Hz, 2H), 7.27 (d, J = 8.6 Hz, 2H), 5.02 (s, 1H), 4.77 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.52 (t, J =7.5 Hz, 1H), 4.38 – 4.29 (m, 2H), 3.33 (s, 3H), 2.70 (q, J = 7.6 Hz, 2H), 1.50(s, 3H), 1.33 (s, 3H), 1.25 (t, J = 7.6 Hz, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.2,149.1, 128.9, 126.9, 126.2, 111.5, 108.4, 84.3, 83.3, 80.9, 63.9, 53.9, 28.0,25.4, 24.0, 14.2.HRMS(ESI) m / z ([M+H] + ) calcd for C 18 H 25 O6: 337.1646. Found:337.1646. Embodiment 4: Aromatic aldehyde 1d (59.3 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3d (45.5 mg, 0.130 mmol, yield 65%). 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.5 Hz, 2H), 7.29 (d, J = 8.3 Hz,2H), 5.02 (s, 1H), 4.76 (d, J = 6.8 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.52 (t, J =6.9 Hz, 1H), 4.34 (dd, J = 7.0, 2.4 Hz, 2H), 3.34 (s, 3H), 2.99 – 2.94 (m, 1H), 1.50 (s, 3H), 1.33 (s, 3H), 1.27 (s, 3H), 1.26 (s, 3H). 13 C NMR(101 MHz, CDCl3)δ 165.2, 153.6, 128.9, 126.3, 125.5, 111.5, 108.4, 84.3, 83.3, 80.9, 63.9,53.9, 33.3, 25.4, 24.0, 22.7.HRMS(ESI) m / z ([M+H] + ) calcd for C 19 H 27 O6:351.1802. Found: 351.1802. Embodiment 5: Aromatic aldehyde 1e (64.9 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3e (54.4 mg, 0.144 mmol, yield 72%). 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.8 Hz, 2H), 7.46 (d, J = 8.8 Hz, 2H), 5.02 (s, 1H), 4.76 (d, J = 5.9 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.51 (d, J =6.9 Hz, 1H), 4.34 (dd, J = 7.0, 2.0 Hz, 2H), 3.34 (s, 3H), 1.50 (s, 3H), 1.34 (s, 9H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 166.2, 156.9, 129.6, 127.0,125.4, 112.6, 109.4, 85.3, 84.4, 81.9, 64.9, 54.9, 35.1, 31.1, 26.5,25.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 20 H 29 O6: 365.1959. Found: 365.1960. Embodiment 6: Aromatic aldehyde 1f (58.5 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3f (36.2 mg, 0.104 mmol, yield 52%). 1 H NMR (400 MHz, CDCl3) δ 7.95 (d, J = 8.5 Hz, 2H), 7.10 (d, J = 8.4 Hz,2H), 5.01 (s, 1H), 4.76 (d, J = 7.1 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.52 (t, J =7.4 Hz, 1H), 4.33 (dd, J = 6.9, 3.6 Hz, 2H), 3.33 (s, 3H), 1.94 (ddd, J = 13.4,8.4, 5.0 Hz, 1H), 1.50 (s, 3H), 1.33 (s, 3H), 1.08 – 1.03 (m, 2H), 0.79 –0.75 (m, 2H). 13 C NMR (101 MHz, CDCl3) δ166.2, 150.4, 129.8, 126.8, 125.4,112.6, 109.4, 85.3, 84.4, 81.9, 64.9, 54.9, 26.5, 25.0, 15.8, 10.4.HRMS(ESI)m / z ([M+H] + ) calcd for C 19 H 25 O6: 349.1646. Found: 349.1647. Embodiment 7: Aromatic aldehyde 1g (49.6mg, 0.40mmol), glycoside 2a (40.8mg, 0.20mmol), cuprous diphenyl phosphate (5.6mg, 0.01mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5mg, 0.015mmol), di-tert-butyl peroxide (117.0mg, 400mol%), triethylenediamine (78.5mg, 350mol%) were added to the reaction bottle, cyclohexane (1mL) was added to dissolve, and the reaction was stirred at 90°C under nitrogen environment for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain 3 g (37.8 mg, 0.116 mmol, yield 58%) of the target colorless liquid product. 1 H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.9, 5.4 Hz, 2H), 7.12 (t, J = 8.7Hz, 2H), 5.02 (s, 1H), 4.76 (d, J = 5.9 Hz, 1H), 4.65 (d, J = 5.9 Hz, 1H), 4.52(t, J = 7.4 Hz, 1H), 4.39 – 4.30 (m, 2H), 3.33 (s, 3H), 1.50 (s, 3H), 1.34 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 167.2, 165.2, 132.4, 115.7, 115.5, 112.7, 109.5,85.3, 84.3, 81.9, 65.3, 55.0, 26.5, 25.0.HRMS(ESI) m / z ([M+H] + )calcd for C 16 H 20 FO6: 327.1238. Found: 327.1238. Embodiment 8: Aromatic aldehyde 1h (56.2 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C for 12 h under nitrogen atmosphere. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3h (30.1 mg, 0.088 mmol, yield 44%). 1 H NMR (400 MHz, CDCl3) δ 8.00 (d, J = 8.6 Hz, 2H), 7.42 (d, J = 8.6 Hz, 2H), 5.01 (s, 1H), 4.76 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.51 (t, J =6.9 Hz, 1H), 4.39 – 4.30 (m, 2H), 3.32 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 CNMR(101 MHz, CDCl3) δ 164.3, 138.7, 130.1, 127.8, 127.2, 111.6, 108.4, 84.2,83.3, 80.8, 64.3, 53.9, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 16 H 20 ClO6:343.0943. Found: 343.0944. Embodiment 9: Aromatic aldehyde 1i (74.0 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C for 12 h under nitrogen atmosphere. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3i (43.2 mg, 0.112 mmol, yield 56%). 1 H NMR (500 MHz, CDCl3) δ 7.92 (d, J = 8.7 Hz, 2H), 7.58 (d, J = 8.5 Hz,2H), 5.01 (s, 1H), 4.75 (d, J = 7.2 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H), 4.53 –4.49 (m, 1H), 4.39 – 4.30 (m, 2H), 3.32 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR(126 MHz, CDCl3) δ 164.4, 130.8, 130.2, 127.7, 127.3, 111.6, 108.5,80.8, 64.4, 53.9, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 16 H 20 BrO6:387.0438. Found: 387.0438. Embodiment 10: Aromatic aldehyde 1j (92.8 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C for 12 h under nitrogen atmosphere. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3j (39.1 mg, 0.090 mmol, yield 45%). 1 H NMR (400 MHz, CDCl3) δ 7.79 (q, J = 8.7 Hz, 4H), 5.01 (s, 1H), 4.75 (d, J = 6.0 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H), 4.51 (t, J = 6.8 Hz, 1H), 4.39 – 4.29(m, 2H), 3.32 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ165.7, 137.8, 131.2, 129.2, 112.7, 109.5, 101.1, 85.3, 84.3, 81.9, 65.4,55.0, 26.5, 25.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 16 H 20 IO6: 435.0299. Found: 435.0298. Embodiment 11: Aromatic aldehyde 1k (65.6 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3k (13.9 mg, 0.038 mmol, yield 19%). 1 H NMR (400 MHz, CDCl3) δ 8.15 – 8.09 (m, 4H), 5.02 (s, 1H), 4.77 (d, J =5.9 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 6.8 Hz, 1H), 4.43 – 4.33 (m,2H), 3.95 (s, 3H), 3.33 (s, 3H), 1.50 (s, 3H), 1.34 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.3, 165.4, 134.1, 133.5, 129.7, 129.6, 112.7, 109.5, 85.3, 84.3,81.9, 65.5, 55.0, 52.5, 26.5, 25.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 18 H 23 O8:367.1387. Found: 367.1388. Embodiment 12: Aromatic aldehyde 1l (79.3 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C for 12 h under nitrogen atmosphere. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3l (46.4 mg, 0.116 mmol, yield 58%). 1 H NMR (400 MHz, CDCl3) δ 8.03 (d, J = 9.0 Hz, 2H), 7.39 (t, J = 8.0 Hz,2H), 7.22 – 7.17 (m, 1H), 7.07 (d, J = 7.5 Hz, 2H), 6.99 (d, J = 8.9 Hz, 2H), 5.02 (s, 1H), 4.76 (d, J = 6.0 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.52 (t, J = 6.9Hz, 1H), 4.33 (dd, J = 6.9, 2.4 Hz, 2H), 3.33 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.6, 162.1, 155.5, 131.9, 130.1, 124.6, 124.0,120.2, 117.3, 112.6, 109.4, 85.3, 84.4, 81.9, 65.0, 55.0, 26.5, 25.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 22 H 25 O7: 401.1595. Found: 401.1598. Embodiment 13: Aromatic aldehyde 1m (53.6 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3m (46.4 mg, 0.138 mmol, yield 69%). 1 H NMR (400 MHz, CDCl3) δ 7.84 – 7.78 (m, 2H), 7.19 (d, J = 7.9 Hz, 1H), 5.02 (s, 1H), 4.77 (d, J = 6.9 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 6.9Hz, 1H), 4.37 – 4.28 (m, 2H), 3.34 (s, 3H), 2.31 (d, J = 3.4 Hz, 6H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.4, 141.6, 135.8, 129.7, 128.7,126.3, 111.5, 108.4, 84.3, 83.4, 80.9, 63.9, 53.9, 25.4, 24.0, 19.0,18.7.HRMS(ESI) m / z ([M+H] + ) calcd for C 18 H 25 O6: 337.1646. Found: 337.1646. Embodiment 14: Aromatic aldehyde 1n (70.0 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3n (45.1 mg, 0.120 mmol, yield 60%). 1 H NMR (400 MHz, CDCl3) δ 8.15 (d, J = 2.0 Hz, 1H), 7.89 (dd, J = 8.4, 2.0Hz, 1H), 7.53 (d, J = 8.4 Hz, 1H), 5.02 (s, 1H), 4.75 (d, J = 6.0 Hz, 1H), 4.65(d, J = 6.0 Hz, 1H), 4.51 (t, J = 7.3 Hz, 1H), 4.36 (dd, J = 6.8, 4.1 Hz, 2H), 3.33(s, 3H), 1.50 (s, 3H), 1.34 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 163.3, 136.9,132.0, 130.6, 129.6, 128.6, 127.8, 111.7, 108.5, 84.2, 83.2, 80.8, 64.7,54.0, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 16 H 19 Cl2O6: 377.0553. Found:377.0555. Embodiment 15: Aromatic aldehyde 1o (71.2 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C for 12 h under nitrogen atmosphere. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3o (23.8 mg, 0.060 mmol, yield 30%). 1 H NMR (500 MHz, CDCl3) δ 7.72 – 7.68 (m, 2H), 7.10 (d, J = 8.1 Hz, 1H), 5.02 (s, 1H), 4.75 (d, J = 7.2 Hz, 1H), 4.65 (d, J = 6.0 Hz, 1H), 4.53 (t, J = 7.2Hz, 1H), 4.35 (d, J = 6.7 Hz, 2H), 3.89 (s, 3H), 3.34 (s, 3H), 2.33 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR (126 MHz, CDCl3) δ167.5, 164.5, 150.1,142.8, 127.4, 121.8, 112.5, 111.6, 108.5, 84.3, 83.3, 80.8, 64.4, 55.1, 53.9,25.4, 24.0, 19.6.HRMS(ESI) m / z ([M+H] + ) calcd for C 19 H 25 O9: 397.1493. Found:397.1493. Embodiment 16: Aromatic aldehyde 1p (70.5 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3p (19.4 mg, 0.052 mmol, yield 26%). 1 H NMR (400 MHz, CDCl3) δ 5.00 (s, 1H), 4.70 (d, J = 6.0 Hz, 1H), 4.63 (d, J = 5.9 Hz, 1H), 4.50 – 4.45 (m, 1H), 4.40 (dd, J = 11.0, 6.6 Hz, 1H), 4.27 (dd, J = 11.0, 8.1 Hz, 1H), 3.36 (s, 3H), 2.23 (s, 3H), 2.19 (d, J = 2.1 Hz, 12H), 1.48 (s, 3H), 1.31 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 170.1, 135.3, 131.8,131.5, 128.1, 111.5, 108.3, 84.1, 83.1, 81.0, 64.1, 54.0, 25.4, 23.9, 17.4,16.7, 15.7, 15.1.HRMS(ESI) m / z ([M+H] + ) calcd for C 21 H 31 O6: 379.2115. Found:379.2115. Embodiment 17: Aromatic aldehyde 1q (72.9 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3q (27.7 mg, 0.072 mmol, yield 36%). 1 H NMR (400 MHz, CDCl3) δ 8.14 (d, J = 8.6 Hz, 2H), 7.67 (d, J = 8.6 Hz,2H), 7.63 (d, J = 7.0 Hz, 2H), 7.47 (t, J = 7.4 Hz, 2H), 7.41 (d, J = 7.4 Hz, 1H), 5.04 (s, 1H), 4.80 (d, J = 6.0 Hz, 1H), 4.67 (d, J = 5.9 Hz, 1H), 4.56 (t, J = 7.5Hz, 1H), 4.43 – 4.33 (m, 2H), 3.36 (s, 3H), 1.52 (s, 3H), 1.35 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.0, 144.9, 138.9, 129.2, 127.9, 127.4, 127.2, 126.3,126.1, 111.6, 108.4, 84.3, 83.3, 80.9, 64.1, 53.9, 25.4, 24.0.HRMS(ESI) m / z([M+H] + ) calcd for C 22 H 25 O6: 385.1646. Found: 385.1645. Embodiment 18: Aromatic aldehyde 1r (59.2 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3r (17.5 mg, 0.050 mmol, yield 25%). 1 H NMR (400 MHz, CDCl3) δ 7.90 (d, J = 7.9 Hz, 2H), 6.79 (d, J = 8.9 Hz,1H), 5.01 (s, 1H), 4.76 (d, J = 4.9 Hz, 1H), 4.68 – 4.63 (m, 3H), 4.51 (t, J =7.6 Hz, 1H), 4.30 (dd, J = 7.0, 2.4 Hz, 2H), 3.33 (s, 3H), 3.24 (t, J = 8.8 Hz, 2H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 165.0, 163.4, 130.3,126.4, 125.9, 121.1, 111.6, 108.4, 108.1, 84.3, 83.4, 80.9, 71.1, 63.8, 53.9,28.0, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 18 H 23 O7: 351.1438. Found:351.1438. Embodiment 19: Aromatic aldehyde 1s (65.6 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3s (35.2 mg, 0.096 mmol, yield 48%). 1 H NMR (400 MHz, CDCl3) δ 7.59 (d, J = 7.9 Hz, 2H), 6.89 (d, J = 8.8 Hz,1H), 5.01 (s, 1H), 4.75 (d, J = 6.0 Hz, 1H), 4.64 (d, J = 6.0 Hz, 1H), 4.50 (t, J =6.9 Hz, 1H), 4.33 – 4.29 (m, 4H), 4.28 (d, J = 5.5 Hz, 2H), 3.33 (s, 3H), 1.49 (s, 3H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 164.6, 147.0, 142.1, 122.6,122.0, 118.1, 116.2, 111.5, 108.4, 84.3, 83.3, 80.9, 63.9, 63.6, 63.1, 53.9,25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 18 H 23 O8: 367.1387. Found:367.1388. Embodiment 20: Aromatic aldehyde 1t (44.8 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3t (23.2 mg, 0.074 mmol, yield 37%). 1 H NMR (400 MHz, CDCl3) δ 8.17 (d, J = 3.1 Hz, 1H), 7.55 (d, J = 6.4 Hz,1H), 7.31 (dd, J = 5.1, 3.1 Hz, 1H), 5.01 (s, 1H), 4.75 (d, J = 6.0 Hz, 1H), 4.64(d, J = 5.9 Hz, 1H), 4.50 (t, J = 6.8 Hz, 1H), 4.31 (d, J = 6.8 Hz, 2H), 3.34 (s, 3H), 1.50 (s, 3H), 1.33 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 161.2, 132.2, 126.9,125.1, 111.6, 108.4, 84.3, 83.3, 80.9, 63.8, 53.9, 25.4, 24.0.HRMS(ESI) m / z([M+H] + ) calcd for C 14 H 19 O6S: 315.0897. Found: 315.0898. Embodiment 21: Aromatic aldehyde 1u (92.1 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:14, v / v) to obtain a colorless liquid target product 3u (27.7 mg, 0.064 mmol, yield 32%). 1 H NMR (400 MHz, CDCl3) δ 9.31 (d, J = 9.4 Hz, 1H), 8.70 (d, J = 8.1 Hz,1H), 8.29 – 8.24 (m, 3H), 8.20 – 8.16 (m, 2H), 8.10 – 8.05 (m, 2H), 5.09 (s,1H), 4.89 (d, J = 5.9 Hz, 1H), 4.74 – 4.71 (m, 1H), 4.68 (d, J = 7.0 Hz, 1H), 4.59 – 4.50 (m, 2H), 3.42 (s, 3H), 1.54 (s, 3H), 1.36 (s, 3H). 13 C NMR (101 MHz, CDCl3) δ 166.4, 133.5, 130.4, 130.0, 129.3, 128.8, 128.6, 127.6, 126.1,125.4, 125.3, 125.3, 123.8, 123.1, 121.8, 111.6, 108.5, 84.3, 83.5, 81.0,64.3, 54.0, 25.5, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 26 H 27 O6: 435.1802.Found: 435.1802. Embodiment 22: Aromatic aldehyde 1v (87.3 mg, 0.40 mmol), glycoside 2a (40.8 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:14, v / v) to obtain a colorless liquid target product 3v (35.3 mg, 0.084 mmol, yield 42%). 1 H NMR (400 MHz, CDCl3) δ 8.67 (d, J = 8.5 Hz, 1H), 8.35 (d, J = 7.4 Hz,1H), 7.59 (d, J = 6.9 Hz, 1H), 7.36 (d, J = 6.9 Hz, 1H), 7.31 (d, J = 7.4 Hz, 1H),5.05 (s, 1H), 4.83 (d, J = 6.0 Hz, 1H), 4.68 (d, J = 6.0 Hz, 1H), 4.61 (t, J = 7.6Hz, 1H), 4.48 – 4.38 (m, 2H), 3.42 (s, 4H), 3.37 (s, 3H), 1.52 (s, 3H), 1.34(s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.7, 152.3, 145.3, 138.5, 132.4, 129.3,129.0, 120.9, 120.5, 119.0, 117.4, 111.6, 108.4, 84.3, 83.4, 80.9, 63.8,53.9, 29.5, 25.4, 24.0.HRMS(ESI) m / z ([M+H] + ) calcd for C 25 H 25O6: 421.1646.Found: 421.1646. Embodiment 23: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2b (52.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:18, v / v) to obtain a colorless liquid target product 3w (39.4 mg, 0.128 mmol, yield 64%). 1 H NMR (400 MHz, CDCl3) δ 8.08 – 8.02 (m, 2H), 7.56 (t, J = 7.4 Hz, 1H),7.43 (t, J = 7.6 Hz, 2H), 5.57 (d, J = 4.9 Hz, 1H), 4.65 (dd, J = 7.9, 2.5 Hz, 1H),4.53 (dd, J = 11.5, 4.9 Hz, 1H), 4.43 (dd, J = 11.5, 7.5 Hz, 1H), 4.36 – 4.31 (m,2H), 4.19 (t, J = 6.2 Hz, 1H), 1.50 (d, J = 15.3 Hz, 6H), 1.35 (d, J = 9.3 Hz, 6H). 13 C NMR (101 MHz, CDCl3) δ 166.5, 133.0, 130.1, 129.7, 128.4, 109.7, 108.8,96.4, 71.2, 70.7, 70.5, 66.2, 63.9, 26.0, 25.0, 24.5.HRMS(ESI) m / z ([M+Na] +)calcd for C 19 H 24 NaO7: 387.1414. Found: 387.1414. Embodiment 24: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2c (52.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:18, v / v) to obtain a colorless liquid target product 3x (35.7 mg, 0.098 mmol, yield 49%). 1 H NMR (400 MHz, CDCl3) δ 8.10 – 8.04 (m, 2H), 7.56 (t, J = 7.4 Hz, 1H),7.44 (t, J = 7.7 Hz, 2H), 4.69 (d, J = 11.9 Hz, 1H), 4.64 (dd, J = 7.9, 2.7 Hz,1H), 4.47 (d, J = 2.6 Hz, 1H), 4.33 (d, J = 11.8 Hz, 1H), 4.26 (d, J = 7.9 Hz, 1H),3.96 (dd, J = 13.0, 2.0 Hz, 1H), 3.81 (d, J = 13.0 Hz, 1H), 1.55 (s, 3H), 1.46(s, 3H), 1.37 (s, 3H), 1.35 (s, 3H). 13C NMR (101 MHz, CDCl3) δ165.0, 132.1,128.7, 127.4, 108.2, 107.8, 100.7, 69.8, 69.5, 69.1, 64.3, 60.3, 25.5, 24.9,24.5, 23.0.HRMS(ESI) m / z ([M+Na] + ) calcd for C 19 H 24 NaO7: 387.1414. Found: 387.1414. Embodiment 25: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2d (52.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3y (26.2 mg, 0.072 mmol, yield 36%). 1 H NMR (400 MHz, CDCl3) δ 8.01 (d, J = 7.0 Hz, 2H), 7.59 (t, J = 7.4 Hz,1H), 7.45 (t, J = 7.8 Hz, 2H), 6.37 (s, 1H), 4.94 (dd, J = 5.9, 3.6 Hz, 1H), 4.88(d, J = 5.9 Hz, 1H), 4.44 (ddd, J = 8.0, 6.1, 4.3 Hz, 1H), 4.14 – 4.09 (m, 2H), 4.05 (dd, J = 8.9, 4.3 Hz, 1H), 1.53 (s, 3H), 1.46 (s, 3H), 1.38 (d, J= 2.9 Hz,6H). 13 C NMR(101 MHz, CDCl3) δ 163.9, 132.5, 128.8, 128.4, 127.5, 112.3, 108.4,100.5, 84.2, 81.5, 78.4, 71.9, 65.9, 26.0, 25.0, 24.1, 23.7.HRMS(ESI) m / z ([M+Na] + ) calcd for C 19 H 24 NaO7: 387.1414. Found: 387.1416. Embodiment 26: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2e (52.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:18, v / v) to obtain a colorless liquid target product 3z (43.7 mg, 0.120 mmol, yield 60%). 1 H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.4, 1.4 Hz, 2H), 7.56 (t, J = 7.4Hz, 1H), 7.44 (t, J = 7.7 Hz, 2H), 4.80 (d, J = 11.9 Hz, 1H), 4.58 (s, 1H), 4.49(d, J = 12.0 Hz, 1H), 4.37 (d, J = 2.9 Hz, 1H), 4.16 (d, J= 2.0 Hz, 1H), 4.11 –4.03 (m, 2H), 1.52 (s, 3H), 1.44 (s, 3H), 1.36 (d, J = 7.6 Hz, 6H). 13 C NMR(101MHz, CDCl3) δ 164.9, 132.1, 128.7, 127.4, 111.9, 111.5, 96.5, 83.5, 72.3,71.5, 62.7, 59.2, 27.8, 26.5, 25.7, 17.7.HRMS(ESI) m / z ([M+Na] + )calcd for C 19 H 24 NaO7: 387.1414. Found: 387.1412. Embodiment 27: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2f (150.3 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:18, v / v) to obtain a colorless liquid target product 3za (34.0 mg, 0.054 mmol, yield 27%). 1 H NMR (400 MHz, CDCl3) δ 8.07 (d, J = 8.1 Hz, 2H), 7.60 (t, J = 6.8 Hz,1H), 7.46 (t, J = 7.8 Hz, 2H), 7.36 – 7.24 (m, 14H), 7.21 (s, 4H), 7.18 – 7.12(m, 2H), 5.95 – 5.83 (m, 1H), 5.30 (s, 1H), 4.93 (d, J= 11.0 Hz, 1H), 4.89 –4.75 (m, 4H), 4.59 (dd, J = 28.2, 11.4 Hz, 2H), 4.48 (d, J = 12.1 Hz, 1H), 3.78(dd, J = 6.7, 3.2 Hz, 2H), 3.67 (d, J = 9.3 Hz, 1H). 13 C NMR (101 MHz, CDCl3) δ163.9 137.4, 137.0, 136.8, 136.7, 132.5, 129.0, 128.2, 127.4, 127.4, 127.4,127.4, 127.3, 127.0, 127.0, 126.9, 126.8, 126.8, 126.7, 126.7, 93.7, 83.9,79.9, 76.2, 74.7, 74.6, 74.0, 74.00, 72.5, 67.0.HRMS(ESI) m / z ([M+H] + ) calcdfor C 40 H 39 O7: 631.2690. Found: 631.2691. Embodiment 28: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2 g (52.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:20, v / v) to obtain a colorless liquid target product 3zb (19.7 mg, 0.054 mmol, yield 27%). 1 H NMR (400 MHz, CDCl3) δ 8.09 (dd, J = 8.4, 1.4 Hz, 2H), 7.58 (t,J = 7.4Hz, 1H), 7.45 (t, J = 7.7 Hz, 2H), 5.39 (d, J = 8.0 Hz, 1H), 4.46 (dd, J = 8.0, 5.3Hz, 1H), 4.29 (q, J = 3.0 Hz, 1H), 4.23 – 4.12 (m, 2H), 4.01 (d, J = 9.3 Hz, 1H),3.89 (d, J = 9.3 Hz, 1H), 1.61 (s, 3H), 1.51 (s, 3H), 1.41 (s, 3H), 1.37 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 166.0, 133.4, 129.9, 129.5, 128.5, 112.2, 109.8,103.9, 75.1, 73.8, 71.7, 70.6, 60.4, 27.9, 26.5, 26.4, 26.2.HRMS(ESI) m / z ([M+H] + ) calcd for C 19 H 25 O7: 365.1595. Found: 365.1594. Embodiment 29: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2h (56.1 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, and cyclohexane (1 mL) was added to dissolve the mixture. The mixture was stirred at 90 °C under nitrogen for 12 h. After the reaction was completed, dichloromethane (10 g) was added, the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:15, v / v) to obtain a colorless liquid target product 3zc (34.6 mg, 0.090 mmol, yield 45%). 1 H NMR (400 MHz, CDCl3) δ 7.99 (d,J = 7.1 Hz, 2H), 7.54 (t, J = 7.4 Hz,1H), 7.40 (t, J = 7.8 Hz, 2H), 7.30 – 7.23 (m, 5H), 5.98 (d, J = 3.8 Hz, 1H),4.70 (d, J = 12.0 Hz, 1H), 4.64 (d, J = 3.9 Hz, 1H), 4.60 (dd, J = 8.8, 5.4 Hz,1H), 4.55 – 4.49 (m, 3H), 4.03 (d, J = 2.9 Hz, 1H), 1.49 (s, 3H), 1.32 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.3, 136.1, 132.0, 128.8, 128.7, 127.5, 127.3,127.0, 126.8, 110.8, 104.3, 81.0, 80.4, 77.1, 70.9, 61.4, 25.8, 25.2.HRMS(ESI) m / z ([M+H] + ) calcd for C 22 H 25 O6: 385.1646. Found: 385.1646. Embodiment 30: Aromatic aldehyde 1a (42.4 mg, 0.40 mmol), glycoside 2i (58.9 mg, 0.20 mmol), cuprous diphenyl phosphate (5.6 mg, 0.01 mmol), 2,2'-bipyridine-4,4'-dimethoxy (6.5 mg, 0.015 mmol), di-tert-butyl peroxide (117.0 mg, 400 mol%), and triethylenediamine (78.5 mg, 350 mol%) were added to a reaction flask, cyclohexane (1 mL) was added to dissolve, and the reaction was stirred at 90 °C under nitrogen for 12 hours. After the reaction was completed, dichloromethane (10 g) was added, and the mixture was stirred thoroughly and allowed to stand for stratification. The organic layer was dried over anhydrous sodium sulfate, filtered, and concentrated to obtain a brown crude product. The crude product was purified by column method (eluent: ethyl acetate / petroleum ether = 1:15, v / v) to obtain a colorless liquid target product 3zd (51.8 mg, 0.130 mmol, yield 65%). 1H NMR (400 MHz, CDCl3) δ 8.05 – 7.99 (m, 4H), 7.61 – 7.52 (m, 2H), 7.43 (dt, J = 12.5, 7.8 Hz, 4H), 6.06 (d, J = 3.8 Hz, 1H), 5.60 (d, J = 3.1 Hz,1H), 4.77 (td, J = 6.0, 3.0 Hz, 1H), 4.70 (d, J = 3.8 Hz, 1H), 4.67 – 4.57 (m,2H), 1.58 (s, 3H), 1.35 (s, 3H). 13 C NMR(101 MHz, CDCl3) δ 165.1, 164.2, 132.7,132.2, 128.8, 128.5, 127.9, 127.6, 127.3, 111.4, 104.1, 82.4, 60.9, 25.7,25.2.HRMS(ESI) m / z ([M+H] + ) calcd for C 22 H 23 O7: 399.1438. Found: 399.1438. In addition, it should be understood that after reading the above description of the present invention, those skilled in the art may make various changes or modifications to the present invention, and these equivalent forms also fall within the scope defined by the claims attached to this application.

Claims

1. A method for preparing a C-acyl glycoside compound, characterized in that: The preparation method comprises the following steps: Aromatic aldehyde 1 is used as raw material, glycoside 2 is used as alkyl source, and a catalyst, ligand, hydrogen transfer reagent, base, and solvent are added to the reaction bottle at the same time, and a coupling reaction is carried out in a nitrogen atmosphere to obtain C-acyl glycoside compound 3; The synthetic route is as follows: Wherein, R is an aryl group or a heteroaryl group, PG is a protecting group, and glycoside 2 is a furanose or a pyranose.

2. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The catalyst is a copper salt selected from one of CuCl, CuI, Cu(acac)2, CuPO2Ph2, Cu2SO4, Cu2S, Cu(NO3)2, and CuCl2.

3. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The ligand is a nitrogen ligand or a phosphorus ligand, wherein the nitrogen ligand is selected from one of 2,2'-bipyridine-4,4'-dicarboxylic acid, 2,2'-bipyridine-4,4'-dimethyl, 2,2'-bipyridine-4,4'-di-tert-butyl, 2,2'-bipyridine-4,4'-dimethoxy, 1,10-phenanthroline, and 2,9-dimethyl-1,10-phenanthroline; and the phosphorus ligand is selected from one of 1,2-bis(diphenylphosphino)ethane and 1,2-bis(dimethylphosphino)ethane.

4. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The hydrogen transfer agent is selected from one of di-tert-butyl peroxide, dibenzoyl peroxide, di-tert-amyl peroxide, tert-butyl peroxybenzoate and tert-butyl hydroperoxide.

5. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The base is an organic base or an inorganic base, wherein the organic base is selected from one of 4-dimethylaminopyridine, N,N-diisopropylethylamine, triethylamine, and triethylenediamine; the inorganic base is selected from one of Na2CO3, Cs2CO3, K2CO3, Li2CO3, and K2PO4.

6. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The solvent is selected from one of N-methylpyrrolidone, N,N-dimethylformamide, N,N-dimethylacetamide, tetrahydrofuran, toluene, n-hexane and cyclohexane.

7. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The molar ratio of the aromatic aldehyde 1, the glycoside 2, the metal catalyst, the ligand, the hydrogen source and the base is 1-3:1-3:0.05-0.2:0.05-0.3:1-10:1-10.

8. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The molar volume ratio of the aromatic aldehyde 1 to the solvent is 0.4 mmol:1-10 mL.

9. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The temperature of the coupling reaction is 50-120°C.

10. The method for preparing C-acyl glycoside compounds according to claim 1, characterized in that: The coupling reaction time is 1 to 24 hours.

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