CN111233810A - Preparation method and application of a class of hydroxycinnamoyl ester catechins - Google Patents

Abstract

The invention relates to a preparation method of hydroxycinnamoyl ester type catechin and application thereof, wherein the hydroxycinnamoyl ester type catechin comprises 4 kinds of catechin, namely epicatechin trans-coumarate, epicatechin trans-caffeate, epigallocatechin trans-coumarate and epigallocatechin trans-caffeate, the 4 kinds of hydroxycinnamoyl ester type catechin are prepared by respectively esterifying and removing protective groups of acetylated caffeic acid or acyl chloride of coumaric acid after the steps of total acetylation, acetyl removal on phenolic hydroxyl, phenolic hydroxyl silanization and 3-bit acetyl removal of epicatechin and epigallocatechin, the preparation method of the 4 kinds of catechin is simple and mild in condition, and can be completed under general experimental conditions, the 4 kinds of hydroxycinnamoyl ester type catechin has a certain inhibition effect on the activity of α -glucosidase, can be used for hypoglycemic drugs, and has important significance to the fields of agriculture and medicine.

Description

Preparation method and application of a class of hydroxycinnamoyl ester catechins

technical field

The invention belongs to the technical field of natural medicinal chemistry, and specifically relates to four kinds named epicatechin trans-coumarate, epicatechin trans-caffeate, epigallocatechin trans-coumarate and epicatechin trans-coumarate respectively. Preparation method and application of hydroxycinnamoyl ester type catechin of gallocatechin transcaffeate.

Background technique

Tea leaves are rich in tea polyphenols, accounting for 18%-36% of the dry matter of tea leaves. Among them, most of them are catechins (flavanols), which account for 12%-24% of the dry matter of tea leaves. Studies have shown that catechins are important taste substances in tea. Moreover, catechins also have pharmacological functions such as anti-inflammatory, antioxidant, anticancer, cardiovascular and neuroprotective effects.

Chemical synthesis experiments usually require special reaction conditions, and the chemical reagents used in the reaction are usually dangerous. The synthesis method of this type of catechin disclosed in the prior art is complicated, and the reaction conditions are harsh, and the conditions of the general laboratory cannot meet the reaction requirements, and the preparation cannot be completed. How to screen the existing preparation methods and reaction raw materials, and design the preparation methods of the four hydroxycinnamoyl ester catechins with simple methods and mild conditions, is of great significance.

SUMMARY OF THE INVENTION

The technical problem to be solved by the present invention is to overcome the deficiencies in the prior art and provide a preparation method of a class of hydroxycinnamoyl ester catechins.

Another technical problem to be solved by the present invention is to provide a class of hydroxycinnamoyl ester catechins prepared by the above method for inhibiting α-glucosidase, which can be applied to the preparation of hypoglycemic drugs.

For solving the technical problem of the present invention, the provided technical scheme is:

A preparation method of a class of hydroxycinnamoyl ester catechins, the class of hydroxycinnamoyl ester catechins includes 4 kinds of catechins, and the names of the 4 kinds of catechins are epicatechin trans-coumaric acid respectively Ester i.e. (–)-epicatechin 3-O-p-coumaroate, epicatechin trans-caffeate i.e. (–)-epicatechin3-O-caffeoate, epigallocatechin trans-coumarate i.e. (–)-epigallocatechin3 -O-p-coumaroate, epigallocatechin trans-caffeate is (–)-epigallocatechin3-O-caffeoate, and its structural formulas are shown in formula I, formula II, formula III and formula IV respectively,

The preparation method of this class of hydroxycinnamoyl ester catechins comprises the following steps:

S1. Using epicatechin, namely EC, as a raw material, 5, 7, 3' is prepared through four reactions of peracetylation, removal of the acetyl group on the phenolic hydroxyl group, silylation of the phenolic hydroxyl group and removal of the 3-position acetyl group, 4'-O-tetra-tert-butyldimethylsilyl-epicatechin;

Using epigallocatechin (EGC) as raw material, 5,7,3',4 is prepared by four reactions: peracetylation, removal of acetyl group on phenolic hydroxyl group, silylation of phenolic hydroxyl group and removal of 3-position acetyl group. ',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin;

S2, prepare 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate;

Weigh 92.0 mg of 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin prepared in step S1 into a 25 mL round-bottomed flask, add 0.2 mL of dry pyridine, 2.0 mL of dry dichloromethane, 3.0 mL of dry dichloromethane containing 0.18 mmol of 3,4-O-diacetylated caffeoyl chloride was slowly added dropwise in an ice bath, react overnight at room temperature, add an appropriate amount of water and an equal volume of Dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted with petroleum ether:ethyl acetate=30:1 by silica gel column chromatography to obtain 3",4"-O-diacetyl base-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate;

S3. Preparation of 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate;

Weigh 395.0 mg of 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin prepared in step S1 into a 25 mL round-bottomed flask, add 1.5 mL of dry pyridine, 3.0 mL of dry dichloromethane, slowly dropwise add 5.0 mL of dry dichloromethane containing 0.80 mmol of 4-O-acetyl coumaroyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane Extracted with methane three times, the dichloromethane layer was dried with anhydrous sodium sulfate and then concentrated, subjected to silica gel column chromatography, eluted with petroleum ether:ethyl acetate=50:1 to obtain 4"-O-acetyl-5,7 ,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate;

S4. Preparation of 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate ;

Weigh 500.0 mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, slowly dropwise add 8.0 mL of dry dichloromethane containing 1.9 mmol of 3,4-O-diacetylated caffeoyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and extracted three times with an equal volume of dichloromethane, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 30:1 to obtain 3", 4"- O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate;

S5, prepare 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate;

Weigh 370.0 mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, slowly dropwise add 7.0 mL of dry dichloromethane containing 1.5 mmol of 4-O-acetyl coumaroyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and etc. The volume of dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 50:1 to obtain 4"-O-acetyl- 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcoumarate;

S6, preparation of epicatechin transcaffeate;

Weigh 164.0mg of the 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans coffee prepared in step S2 In a 25mL round-bottomed flask, add 28.0mg potassium hydrogen fluoride, then add 6.0mL dry methanol, and react at 50°C for 6 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the Catechin transcaffeate;

S7, preparing epigallocatechin transcaffeate;

Weigh 60.0mg of the 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin obtained in step S4 In a 25 mL round-bottomed flask, 200.0 mg of potassium hydrogen fluoride was added, followed by 5.0 mL of dry methanol, and the reaction was carried out at 50°C for 6 hours. The reaction product was subjected to LH-20 gel column chromatography, washed with methanol. After taking off, epigallocatechin transcaffeate is obtained;

S8, prepare epicatechin trans-coumarate;

Weigh 163.0 mg of 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate prepared in step S3 to In a 25mL round-bottomed flask, add 136.0mg of potassium hydrogen fluoride, then add 6.0mL of dry methanol, and react at room temperature for 3.5 hours. After the reaction is completed, add an appropriate amount of water and extract three times with an equal volume of ethyl acetate. The ethyl acetate layer After drying with anhydrous sodium sulfate, it was concentrated, and eluted by silica gel column chromatography with petroleum ether:ethyl acetate=1:1 to obtain 4"-O-acetyl-epicatechin trans-coumarate;

Weigh 50.0 mg of 4"-O-acetyl-epicatechin trans-coumarate into a 10 mL round-bottomed flask, add 450.0 mg ammonium acetate, add 2.0 mL of 80% methanol aqueous solution, and react at room temperature for 5.5 After 1 hour, the reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain epicatechin trans-coumarate;

S9, prepare epigallocatechin trans-coumarate;

Weigh 130.0 mg of the 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-fragrance prepared in step S5. In a 25mL round-bottomed flask, 476.0mg potassium hydrogen fluoride was added, and then 8.0mL of dry methanol was added, and the reaction was carried out at 50°C for 6 hours. The reaction product was concentrated and subjected to LH-20 gel column chromatography, eluting with methanol. After obtaining 4 "-O-acetyl-epigallocatechin trans-coumarate;

Weigh 36.0 mg of 4"-O-acetyl-epigallocatechin trans-coumarate into a 10 mL round-bottomed flask, add 460.0 mg ammonium acetate, add 2.0 mL of 80% methanol aqueous solution, and react at room temperature After 5 hours, the reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain epigallocatechin trans-coumarate;

The steps S2, S3, S4, and S5 are in no particular order, and the steps S6, S7, S8, and S9 are in no particular order.

As a further improvement of the preparation method of a class of hydroxycinnamoyl ester catechins,

Preferably, the 3,4-O-diacetylated caffeoyl chloride described in step S2 is prepared in the following manner:

Weigh 180.1 mg of caffeic acid into a 25 mL round-bottomed flask, add 0.3 mL of dry pyridine and 0.5 mL of acetic anhydride, and stir overnight at room temperature under the protection of a drying tube. After the reaction is completed, water is added to terminate the reaction, and acetylated caffeic acid, namely 3,4-O-diacetylated caffeic acid, can be obtained after rotary evaporation to dryness; the reacted acetylated caffeic acid is transferred to a 50mL round-bottomed flask. , add 10 mL of thionyl chloride, and heat under reflux at 90° C. for 3 hours to obtain crude 3,4-O-diacetylated caffeoyl chloride, which is stored for later use.

Preferably, the 4-O-acetylated coumaroyl chloride described in step S3 is obtained in the following manner:

Weigh 656.0 mg of coumaric acid into a 25 mL round-bottomed flask, add 0.8 mL of dry pyridine, and 1.0 mL of acetic anhydride, and stir overnight at room temperature under the protection of a drying tube. After the reaction, water was added to terminate the reaction, and acetylated coumaric acid was obtained after rotary evaporation; the reacted acetylated coumaric acid was transferred to a 25 mL round-bottomed flask, 3.0 mL of thionyl chloride was added, and 90 mL of thionyl chloride was added. The crude product 4-O-acetylated coumaroyl chloride can be obtained by heating under reflux for 3 hours, which can be stored for later use.

In order to solve another technical problem of the present invention, another technical solution provided is the use of a class of hydroxycinnamoyl ester catechins prepared by the above preparation method in the preparation of hypoglycemic drugs.

As a further improvement of the use of a class of hydroxycinnamoyl ester catechins in the preparation of hypoglycemic drugs, the hypoglycemic drugs include oral type and injection type, and the oral type includes tablets, capsules, granules, drops, etc. Pills, and the injection type includes injection solution and mixed solution.

Compared with the prior art, the present invention has the following beneficial effects:

1) the invention provides the synthetic method of four kinds of hydroxycinnamoyl ester type catechins, different from the synthetic method of the prior art, the hydroxyl protecting group that this synthetic experiment adopts, esterification reaction conditions and the protection group are used. Hydrolysis conditions have obvious advantages, the preparation method is simple, mild conditions, easy to implement, low cost, and has very good application prospects

2) The four hydroxycinnamoyl ester catechins prepared by the present invention have medical activity, have a certain inhibitory effect on α-glucosidase activity, and can be used to prepare oral and injectable hypoglycemic drugs, which are beneficial to agriculture and medicine. field is important.

Description of drawings

Fig. 1 is the synthetic route of four kinds of hydroxycinnamoyl ester catechins;

The meanings of the symbols in the accompanying drawings are as follows:

1a, 3,5,7,3',4'-O-pentaacetyl-epicatechin

1b, 3,5,7,3',4',5'-O-hexaacetyl-epigallocatechin

2a, 3-O-acetyl-epicatechin

2b, 3-O-acetyl-epigallocatechin

3a, 3-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin

3b, 3-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin

4a, 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin

4b, 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin

5a, 3,4-O-Diacetylated caffeoyl chloride

5b, 4-O-acetylated coumaroyl chloride

6a, 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate

6b, 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate

6c, 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate

6d, 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcoumarate

7a, 4"-O-acetyl-epicatechin trans-coumarate

7b, 4"-O-acetyl-epigallocatechin transcoumarate

8a, epicatechin transcaffeate

8b, epicatechin transcoumarate

8c, epigallocatechin transcaffeate

8d, epigallocatechin transcoumarate

Detailed ways

Below in conjunction with embodiment, the present invention is further described:

This section generally describes the materials and experimental methods used in the experiments of the present invention. While many of the materials and methods of operation used for the purposes of the present invention are known in the art, the present invention is described herein in as much detail as possible. It is clear to those skilled in the art that the materials, equipment and methods of operation used in the present invention are well known in the art if not specifically stated below.

Example 1

Hydroxycinnamoyl ester type catechins of epicatechin transcoumarate, epicatechin transcaffeate, epigallocatechin transcoumarate and epigallocatechin transcaffeate The preparation of tea;

1.1 Instruments and Reagents

The ¹ H nuclear magnetic resonance spectrum was performed by an Agilent DD2600 MHz nuclear magnetic resonance instrument; the mass spectrometer was performed by an Agilent 6465UPLC-Q-TOF-MS.

Epicatechin (EC) and epigallocatechin (EGC) were purchased from Chengdu Biopharmaceutical Co., Ltd. and Hubei Jusheng Technology Co., Ltd. respectively; caffeic acid and p-coumaric acid were purchased from Anaiji Chemical; other reagents were Domestic analytical pure.

1.2 Hydroxycinnamoyl ester catechins of epicatechin transcoumarate, epicatechin transcaffeate, epigallocatechin transcoumarate and epicatechin transcaffeate The synthetic route of tea is shown in Figure 1;

1.3 Specific implementation methods:

Synthesis of compound 1a:

Weigh 1.16 g (4.0 mmol) of epicatechin (EC) into a 50 mL round-bottomed flask, add 6.0 mL of dry pyridine, 8.0 mL of acetic anhydride (84.6 mmol), and stir overnight at room temperature under the protection of a drying tube. After the reaction is completed, water is added to terminate the reaction, and the EC peracetylated product 3,5,7,3',4'-O-pentaacetyl-epicatechin (1a, 1.9g) can be obtained after rotary evaporation to dryness. , white powder, yield 95%). ¹ H NMR (600 MHz, CDCl ₃ ): 7.33 (1H, s), 7.25 (1H, d, J=8.4 Hz), 7.18 (1H, d, J=8.4 Hz), 6.65 (1H, br s), 6.55 (1H,br s),5.37(1H,br s),5.09(1H,s),2.95(1H,dd,J=18.0,4.2Hz),2.87(1H,br d,J=18.0Hz),2.27 (9H,s), 2.26(3H,s), 1.90(3H,s).

Synthesis of compound 1b:

Weigh 1.2 g (3.9 mmol) of epigallocatechin (EGC) into a 50 mL round-bottomed flask, add 6.0 mL of dry pyridine, 10.0 mL of acetic anhydride (105.7 mmol), and stir overnight at room temperature under the protection of a drying tube. After the reaction is completed, add water to terminate the reaction, and after rotary evaporation to dryness, the EGC peracetylation product can be obtained: 3,5,7,3',4',5'-O-hexaacetyl-epigallocatechin (1b, 2.1 g, white powder, 94% yield). ¹ H NMR (600MHz, CDCl ₃ ): 7.20(2H,s), 6.65(1H,brs), 6.55(1H,brs), 5.36(1H,brs), 5.07(1H,s), 2.94(1H , dd, J=18.0, 4.2 Hz), 2.88 (1H, br d, J=17.4 Hz), 2.25-2.28 (15H, m), 1.92 (3H, s).

Synthesis of compound 2a:

Weigh 500.0 mg (1.0 mmol) of compound 1a into a 100 mL round-bottomed flask, add 50 mL of 80% methanol aqueous solution, 7.8 g (101.2 mmol) of ammonium acetate, and stir at room temperature overnight. After the reaction is over, add an appropriate amount of water, spin and concentrate to remove methanol, extract three times with an equal volume of ethyl acetate, concentrate the ethyl acetate layer, perform silica gel column chromatography, and wash with ethyl acetate: methanol = 20:1. After removal, the compound 3-O-acetyl-epicatechin (2a, 259.0 mg, white powder, yield 78%) was obtained. ¹ H NMR (600MHz, DMSO-d ₆ ): 9.29(1H,s), 9.02(1H,s), 8.92(1H,s), 8.83(1H,s), 6.83(1H,s), 6.69(1H,s) d,J=8.4Hz),6.65(1H,d,J=7.8Hz),5.93(1H,s),5.76(1H,s),5.23(1H,br s),4.93(1H,s),2.87 (1H, dd, J=17.4, 4.2 Hz), 2.58 (1H, br d, J=16.8 Hz), 1.87 (3H, s).

Synthesis of compound 2b:

Weigh 4.2 g (1.0 mol) of compound 1b into a 500 mL round-bottomed flask, add 80 mL of 80% methanol aqueous solution, 1.0 g (11.9 mmol) of sodium bicarbonate, and stir at room temperature overnight. After the reaction was completed, an appropriate amount of water was added, extracted three times with an equal volume of ethyl acetate, the ethyl acetate layer was concentrated, subjected to silica gel column chromatography, and eluted with ethyl acetate: methanol = 1:1 to obtain compound 3- O-Acetyl-epigallocatechin (2b, 1.05 mg, white powder, 40% yield). ¹ H NMR (600MHz, DMSO-d ₆ ): 9.25(1H,s), 8.99(1H,s), 8.78(1H,s), 7.99(1H,s), 6.35(2H,s), 5.92(1H ,d,J＝1.2Hz),5.75(1H,d,J＝1.8Hz),5.21(1H,br s),4.85(1H,s),2.87(1H,dd,J＝17.4,4.8Hz), 2.57(1H,br d,J=16.8Hz), 1.88(3H,s).

Synthesis of compound 3a:

Weigh 200.0 mg (0.6 mmol) of compound 2a into a 100 mL round-bottomed flask, add dry dichloromethane 10 mL, 816.0 mg (12.0 mmol) imidazole, 40 mg (0.33 mmol) 4-dimethylaminopyridine, under ice bath conditions 10 mL of a dry dichloromethane solution containing 723.4 mg (4.8 mmol) of tert-butyldimethylsilyl chloride was slowly added dropwise. Stir overnight at room temperature. After the reaction was completed, an appropriate amount of water was added, extracted three times with an equal volume of dichloromethane, the dichloromethane layer solution was washed with saturated sodium chloride, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate=100: 1 After elution, the compound 3-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin (3a, 450.0 mg, transparent oil, received rate 95%). ¹ H NMR (600MHz, CDCl ₃ ): 6.87(1H,s), 6.85(1H,d,J=8.4Hz), 6.79(1H,d,J=7.8Hz), 6.13(1H,brs), 5.96( 1H,br s),5.37(1H,br s),4.94(1H,s),2.90(1H,dd,J=17.4,4.2Hz),2.83(1H,br d,J=18.0Hz),1.87( 3H, s), 0.94-0.98 (36H, m), 0.15-0.21 (24H, m).

Synthesis of compound 3b:

Weigh 500.0 mg (1.4 mmol) of compound 2b into a 100 mL round-bottomed flask, add dry dichloromethane 10 mL, 2.4 g (35.3 mmol) imidazole, 100 mg (0.82 mmol) 4-dimethylaminopyridine, under ice bath conditions 10 mL of a dry dichloromethane solution containing 2.4 g (16.0 mmol) of tert-butyldimethylsilyl chloride was slowly added dropwise. Stir overnight at room temperature. After the reaction was completed, an appropriate amount of water was added, extracted three times with an equal volume of dichloromethane, the dichloromethane layer solution was washed with saturated sodium chloride, concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate=200: 1 After elution, the compound 3-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin (3b, 970.0 mg, transparent oil, yield 74%). ¹ H NMR (600 MHz, CDCl ₃ ): 6.55 (2H,s), 6.11 (1H,d,J=2.4Hz), 5.95 (1H,d,J=2.4Hz), 5.36 (1H,m), 4.91 (1H ,br s),2.89(1H,dd,J＝17.4,4.8Hz),2.81(1H,dd,J＝17.4,3.0Hz),1.86(3H,s),0.90-0.97(45H,m),0.08 -0.21(30H,m).

Synthesis of compound 4a:

Weigh 100.0 mg (0.13 mmol) of compound 3a into a 50 mL round-bottomed flask, dissolve with 100 uL of dry dichloromethane, add 10 mL of dry methanol, 50.0 mg (0.36 mmol) of potassium carbonate, and stir at room temperature for 2 hours. After the reaction was completed, an appropriate amount of water was added, extracted three times with an equal volume of ethyl acetate, the ethyl acetate layer solution was dried with anhydrous sodium sulfate and concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate=100: 1 was eluted to obtain compound 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin (4a, 38.0 mg, transparent oil, yield 40%). ¹ H NMR (600 MHz, CDCl ₃ ): 6.94 (1H, d, J=1.8 Hz), 6.92 (1 H, dd, J=8.4, 1.8 Hz), 6.84 (1 H, d, J=7.8 Hz), 6.11 ( 1H,d,J=2.4Hz), 5.96(1H,d,J=1.8Hz), 4.86(1H,s), 4.20(1H,br s), 2.86(1H,s), 2.85(1H,s) ,0.99(9H,s),0.97(9H,s),0.96(9H,s),0.95(9H,s),0.16-0.22(24H,m).

Synthesis of compound 4b:

Weigh 970.0 mg (1.06 mmol) of compound 3b into a 100 mL round-bottomed flask, dissolve with 100 uL of dry dichloromethane, then add 40 mL of dry methanol, 200 mg (1.44 mmol) of potassium carbonate, and stir at room temperature for 2 hours. After the reaction is over, add an appropriate amount of water, extract three times with an equal volume of ethyl acetate, the ethyl acetate layer solution is dried with anhydrous sodium sulfate and concentrated, and subjected to silica gel column chromatography with petroleum ether:ethyl acetate=200: 1 After elution, compound 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin (4b, 353.0 mg, transparent oil, yield 38%) was obtained ). ¹ H NMR (600 MHz, CDCl ₃ ): 6.59 (2H, s), 6.09 (1H, d, J=1.8 Hz), 5.95 (1H, d, J=2.4 Hz), 4.82 (1H, br s), 4.16 (1H,m),3.47(1H,s),2.85(1H,dd,J=16.8,4.2Hz),2.80(1H,dd,J=16.8,3.0Hz),0.90-0.99(45H,m), 0.10-0.22 (30H, m).

Synthesis of compound 5a:

Weigh 180.1 mg (1.0 mmol) of caffeic acid into a 25 mL round-bottomed flask, add 0.3 mL of dry pyridine, 0.5 mL of acetic anhydride (5.3 mmol), and stir overnight at room temperature under the protection of a drying tube. After the reaction was completed, water was added to terminate the reaction, and acetylated caffeic acid (3,4-O-diacetylated caffeic acid, 250.8 mg, yield 95%) was obtained after rotary evaporation. ¹ H NMR (600 MHz, DMSO-d ₆ ): 12.47 (1H,s) 7.66 (1H,s), 7.63 (1H,d,J=8.4Hz), 7.57 (1H,d,J=16.2Hz), 7.31 (1H,d,J=8.4Hz), 6.53(1H,d,J=16.2Hz), 2.29(3H,s), 2.29(3H,s). The reacted acetylated caffeic acid was transferred to a 50 mL round-bottomed flask, 10 mL of thionyl chloride was added, and the crude compound 3,4-O-diacetylated caffeic acid chloride (5a) was obtained by heating under reflux at 90° C. for 3 hours. used for the next reaction.

Synthesis of compound 5b:

Weigh 656.0 mg (4.0 mmol) of caffeic acid into a 25 mL round-bottomed flask, add 0.8 mL of dry pyridine, 1.0 mL of acetic anhydride (10.6 mmol), and stir overnight at room temperature under the protection of a drying tube. After the reaction was completed, water was added to terminate the reaction, and acetylated coumaric acid (4-O-acetylated coumaric acid, 774.6 mg, yield 94%) was obtained after rotary evaporation. ¹ H NMR (600MHz, DMSO-d ₆ ): 12.36(1H,s) 7.73(2H,d,J=9.0Hz), 7.60(1H,d,J=14.4Hz), 7.18(2H,d,J=14.4Hz) 8.4Hz), 6.50(1H,d,J=16.2Hz), 2.28(3H,s). The reacted acetylated coumaric acid (251.0 mg, 1.2 mmol) was transferred to a 25 mL round-bottomed flask, 3.0 mL of thionyl chloride was added, and the crude compound 4-O-acetylated incense was obtained by heating under reflux at 90° C. for 3 hours. Soyloyl chloride (5b) was used directly in the next reaction.

Synthesis of compound 6a:

Weigh compound 4a (92.0 mg, 0.12 mmol) into a 25 mL round-bottomed flask, add 0.2 mL of dry pyridine, 2.0 mL of dry dichloromethane, and slowly dropwise add compound 5a (0.18 mmol) in an ice bath. Dichloromethane 3.0 mL. The reaction was carried out at room temperature overnight, and an appropriate amount of water and an equal volume of dichloromethane were added for extraction three times. The dichloromethane layer was dried over anhydrous sodium sulfate and concentrated. The silica gel column chromatography was carried out with petroleum ether:ethyl acetate=30:1 for elution. Then the compound 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate (6a, 95.5 mg, oily, yield 78%). ¹ H NMR (600 MHz, CDCl ₃ ): 7.45 (1H, d, J=15.6 Hz), 7.32 (1H, dd, J=8.4, 1.2 Hz), 7.26 (1H, br s), 7.16 (1H, d, J=8.4Hz),6.89(1H,d,J=1.8Hz),6.87(1H,br d,J=8.4Hz),6.77(1H,d,J=8.4Hz),6.26(1H,d,J =16.2Hz),6.15(1H,d,J=2.4Hz),5.96(1H,d,J=1.8Hz),5.50(1H,br s),5.00(1H,s),2.96(1H,dd, J=18, 4.8Hz), 2.90 (1H, br d, J=17.4Hz), 2.27 (6H,s), 0.92-0.97 (36H,m), 0.12-0.21 (24H,m).

Synthesis of compound 6b:

Weigh compound 4a (395.0 mg, 0.53 mmol) into a 25 mL round-bottomed flask, add 1.5 mL of dry pyridine, 3.0 mL of dry dichloromethane, and slowly dropwise add compound 5b (0.80 mmol) in an ice bath. Dichloromethane 5.0 mL. The reaction was carried out at room temperature overnight, and an appropriate amount of water and an equal volume of dichloromethane were added for extraction three times. The dichloromethane layer was dried over anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography, and washed with petroleum ether:ethyl acetate=50:1. After removal, the compound 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate (6b, 197.8 mg, Oil, yield 40%). ^1H NMR (600MHz, _CDCl3 ): 7.49(1H,d,J=15.6Hz), 7.44(2H,d,J=9.0Hz), 7.07(1H,d,J= 9.0Hz), 6.91(1H,d,J＝1.8Hz), 6.86(1H,dd,J＝8.4,2.4Hz), 6.77(1H,d,J＝8.4Hz), 6.26(1H,d,J＝ 16.2Hz), 6.16(1H,d,J=1.8Hz), 5.97(1H,d,J=2.4Hz), 5.52(1H,br s), 5.01(1H,s), 2.97(1H,dd,J = 17.4, 4.2 Hz), 2.90 (1H, dd, J=16.8, 3.0 Hz), 2.28 (3H, s), 0.92-0.97 (36H, m), 0.12-0.21 (24H, m).

Synthesis of compound 6c:

Weigh compound 4b (500.0 mg, 0.57 mmol) into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, and slowly dropwise add compound 5a (1.9 mmol) in an ice bath. Dichloromethane 8.0 mL. The reaction was carried out at room temperature overnight, and an appropriate amount of water and an equal volume of dichloromethane were added for extraction three times. The dichloromethane layer was dried over anhydrous sodium sulfate and concentrated. The silica gel column chromatography was carried out with petroleum ether:ethyl acetate=30:1 for elution. Then the compound 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate was obtained (6c, 172.1 mg, oil, 70% yield). ¹ H NMR (600 MHz, CDCl ₃ ): 7.44 (1 H, d, J=16.2 Hz), 7.29 (1 H, dd, J=8.4, 1.8 Hz), 7.24 (1 H, s), 7.16 (1 H, d, J =8.4Hz),6.56(2H,s),6.23(1H,d,J=16.2Hz),6.14(1H,d,J=2.4Hz),5.95(1H,d,J=2.4Hz),5.49( 1H,m),4.97(1H,s),2.95(1H,dd,J=17.4,4.8Hz),2.87(1H,dd,J=17.4,3.6Hz),2.26(6H,s),0.86-0.97 (45H,m), 0.04-0.21 (30H,m).

Synthesis of compound 6d:

Weigh compound 4b (370.0 mg, 0.42 mmol) into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, and slowly dropwise add compound 5b (1.5 mmol) in an ice bath. Dichloromethane 7.0 mL. The reaction was carried out at room temperature overnight, and an appropriate amount of water and an equal volume of dichloromethane were added for extraction three times. The dichloromethane layer was dried over anhydrous sodium sulfate and then concentrated. The silica gel column chromatography was carried out with petroleum ether:ethyl acetate=50:1 for elution. The compound 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcoumarate (6d, 280.0 mg, oily, yield 62%). ¹ H NMR (600 MHz, CDCl ₃ ): 7.48 ( ¹ H, d, J=16.2 Hz), 7.43 (2H, d, J=9.0 Hz), 7.07 (2H, d,J=8.4Hz),6.57(2H,s),6.24(1H,d,J=15.6Hz),6.15(1H,d,J=1.8Hz),5.96(1H,d,J=2.4Hz) ,5.50(1H,m),4.97(1H,s),2.95(1H,dd,J＝17.4,4.8Hz),2.88(1H,dd,J＝17.4,3.0Hz),2.28(3H,s), 0.86-0.97(45H,m), 0.04-0.20(30H,m).

Compound 7a synthesis:

Compound 6b (163.0 mg, 0.17 mmol) was weighed into a 25 mL round bottom flask, potassium hydrogen fluoride (136.0 mg, 1.7 mmol) was added, 6.0 mL of dry methanol was added, and the reaction was carried out at room temperature for 3.5 hours. After the reaction was completed, an appropriate amount of water was added, and the mixture was extracted three times with an equal volume of ethyl acetate. The ethyl acetate layer was dried with anhydrous sodium sulfate and concentrated, and eluted with petroleum ether:ethyl acetate=1:1 by silica gel column chromatography to obtain compound 4"-O-acetyl-epicatechin trans-flavor Soyate (7a, 70.9 mg, white powder, 85% yield). ¹ H NMR (600 MHz, DMSO-d ₆ ): 9.27 (1H,s), 9.01 (1H,s), 8.82 (1H,s) ,8.77(1H,s),7.73(2H,d,J=8.4Hz),7.51(1H,dd,J=16.2Hz),7.15(2H,d,J=8.4Hz),6.89(1H,d, J＝1.8Hz), 6.71(1H,dd,J＝8.4,1.8Hz),6.67(1H,d,J＝8.4Hz),6.48(1H,d,J＝16.2Hz),5.94(1H,d, J=1.8Hz),5.81(1H,d,J=1.8Hz),5.36(1H,br s),5.02(1H,s),2.95(1H,dd,J=17.4,4.8Hz),2.68(1H , br d, J=16.8 Hz), 2.27 (3H, s).

Compound 7b synthesis:

Compound 6d (130.0 mg, 0.12 mmol) was weighed into a 25 mL round-bottomed flask, potassium hydrogen fluoride (476.0 mg, 6.1 mmol) was added, 8.0 mL of dry methanol was added, and the reaction was carried out at 50° C. for 6 hours. The reaction product was concentrated and subjected to LH-20 gel column chromatography, eluted with methanol to obtain compound 4"-O-acetyl-epigallocatechin trans-coumarate (7b, 36.0 mg, white powder, collected rate 60%). ^1H NMR (600MHz, _DMSO -d6): 9.29(1H,s), 9.03(1H,s), 8.76(1H,s), 8.00(1H,s), 7.72(2H,d ,J=8.4Hz),7.51(1H,dd,J=16.2Hz),7.15(2H,d,J=9.0Hz),6.46(1H,d,J=16.2Hz),6.40(2H,s), 5.94(1H,d,J＝2.4Hz),5.79(1H,d,J＝2.4Hz),5.34(1H,brs),4.95(1H,s),2.94(1H,dd,J＝17.4,4.8Hz ), 2.67(1H,br d,J=16.2Hz), 2.26(3H,s).

Compound 8a synthesis:

Weigh 6a (164.0 mg, 0.16 mmol) into a 25 mL round-bottomed flask, add potassium hydrogen fluoride (28.0 mg, 1.64 mmol), and then add 6.0 mL of dry methanol, and react at 50° C. for 6 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the compound epicatechin transcaffeate (8a, 52.0 mg, white powder, yield 70%). ¹ H NMR (600MHz, DMSO-d ₆ ): 7.32 (1H,d,J=16.2Hz), 6.98 (1H,s), 6.95 (1H,dd,J=6.6,1.8Hz), 6.88 (1H,s) ),6.73(1H,d,J＝7.8Hz),6.70(1H,dd,J＝8.4,1.2Hz),6.67(1H,dd,J＝7.8Hz),6.12(1H,d,J＝15.6Hz ),5.94(1H,d,J=1.8Hz),5.81(1H,d,J=1.8Hz),5.31(1H,br s),5.01(1H,s),2.92(1H,dd,J=17.4 , 4.8Hz), 2.67 (1H, br d, J=16.2Hz). HR-ESI-MS (negative ion): m/z 451.1040 [MH] ^- .

Synthesis of compound 8b:

Weigh 7a (50.0 mg, 0.1 mmol) into a 10 mL round-bottomed flask, add ammonium acetate (450.0 mg, 5.8 mmol), add 2.0 mL of 80% methanol aqueous solution, and react at room temperature for 5.5 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the compound epicatechin trans-coumarate (8b, 45.6 mg, white powder, yield 88%). 1H NMR (600MHz, DMSO-d ₆ ): 7.50 (2H,d,J=8.4Hz), 7.41 (1H,d,J=15.6Hz), 6.88 (1H,d,J=1.8Hz), 6.75 (2H) ,d,J＝9.0Hz),6.70(1H,dd,J＝8.4,1.2Hz),6.67(1H,d,J＝7.8Hz),6.24(1H,d,J＝15.6Hz),5.93(1H ,d,J＝1.8Hz),5.80(1H,d,J＝1.8Hz),5.32(1H,br s),5.01(1H,s),2.92(1H,dd,J＝17.4,4.8Hz), 2.66 (1H, br d, J=16.2 Hz). HR-ESI-MS (negative ion): m/z 435.1088 [MH] ^- .

Synthesis of compound 8c:

Weigh 6c (60.0 mg, 0.05 mmol) into a 25 mL round-bottom flask, add potassium hydrogen fluoride (200.0 mg, 2.56 mmol), and then add 5.0 mL of dry methanol, and react at 50° C. for 6 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the compound epigallocatechin transcaffeate (8c, 15.0 mg, white powder, yield 60%). ¹ H NMR (600MHz, DMSO-d ₆ ): 7.33 (1H,d,J=16.8Hz), 6.98 (1H,d,J=1.8Hz), 6.96 (1H,dd,J=8.4,1.8Hz), 6.72(1H,d,J＝8.4Hz),6.39(2H,s),6.09(1H,d,J＝16.2Hz),5.93(1H,d,J＝1.8Hz),5.79(1H,d,J = 2.4 Hz), 5.28 (1H, br s), 4.93 (1H, s), 2.90 (1H, dd, J=17.4, 4.8 Hz), 2.64 (1H, br d, J=16.2 Hz). HR-ESI-MS (negative ion): m/z 451.1033 [MH] ^- .

Synthesis of compound 8d:

Weigh 7b (36.0 mg, 0.07 mmol) into a 10 mL round-bottomed flask, add ammonium acetate (460.0 mg, 6.0 mmol), add 2.0 mL of 80% methanol aqueous solution, and react at room temperature for 5 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the compound epigallocatechin trans-coumarate (8d, 18.1 mg, white powder, yield 55%). ¹ H NMR (600 MHz, DMSO-d ₆ ): 7.49 (2H, d, J=8.4 Hz), 7.41 (1H, d, J=15.6 Hz), 6.75 (2H, d, J=8.4 Hz), 6.39 ( 2H,s),6.22(1H,d,J＝15.6Hz),5.93(1H,d,J＝2.4Hz),5.79(1H,d,J＝1.8Hz),5.30(1H,br s),4.93 (1H, s), 2.91 (1H, dd, J=17.4, 4.8 Hz), 2.65 (1H, br d, J=16.2 Hz). HR-ESI-MS (negative ion): m/z 467.0979 [MH] ^- .

Example 2

Epicatechin transcoumarate, epicatechin transcaffeate, epigallocatechin transcoumarate and epigallocatechin transcaffeate prepared in Example 1 Four kinds of hydroxycinnamoyl ester catechins were used to inhibit the activity of α-glucosidase in vitro.

2.1 Experimental materials and reagents

Acarbose, potassium phosphate buffer (PPBS, 10mM, pH 6.9), α-glucosidase (0.1 U·mL ^-1 ), 4-nitrophenyl-α-D-glucopyranoside (pNPG , 2.5mM), dimethyl sulfoxide (DMSO)

2.2 Experimental methods and results

Add 60 μL of α-glucosidase solution to the 96-well plate, and add 60 μL of four hydroxycinnamoyl ester catechins with different concentration gradients respectively. After incubation at 37°C for 20min, place it on a microplate reader (25°C), and record the A value of the reaction solution under visible light with a wavelength of 405 nm. All samples were repeated 3 times and recorded as A sample. The α-glucosidase was replaced with 60 μL of PPBS, recorded as A blank (repeated 3 times), and the blank was adjusted to zero. The sample solution was replaced with 60 μL of PPBS, designated as Test A. The sample solution and α-glucosidase were replaced with 120 μL of PPBS, designated as A control (repeated 3 times).

The enzyme inhibition rate of acetylcholinesterase was calculated according to the following formula:

Inhibition rate (%)=(1-(A sample-A blank)/(A test-A control))×100%.

The relative activity of the enzyme was plotted against the concentration of the inhibitor, and the IC ₅₀ value of the interaction between the four hydroxycinnamoyl ester catechins and α-glucosidase could be calculated according to the inhibition curve. The measured results are shown in the following table:

Note: Positive control drug - acarbose

As can be seen from the results in the table, four hydroxycinnamoyl ester catechins prepared by the present invention: epicatechin transcoumarate, epicatechin transcaffeate, epigallocatechin trans Both coumarate and epigallocatechin transcaffeate have strong inhibitory effects on α-glucosidase, and can be used in the preparation of hypoglycemic drugs, and have broad application prospects.

It should be understood that the examples and embodiments described herein are only for illustration, not for limiting the present invention, and those skilled in the art can make various modifications or changes according to it. Modifications, equivalent replacements, improvements, etc., should all be included within the protection scope of the present invention.

Claims (5)

1. The preparation method of a class of hydroxycinnamoyl ester catechins, the class of hydroxycinnamoyl ester catechins includes 4 kinds of catechins, and the names of these 4 kinds of catechins are epicatechin trans-fragrance respectively. Soyate is (–)-epicatechin 3-O-p-coumaroate, epicatechin trans-caffeate is (–)-epicatechin 3-O-caffeoate, epigallocatechin trans-coumarate is (– )-epigallocatechin 3-O-p-coumaroate, epigallocatechin trans-caffeoate, namely (–)-epigallocatechin 3-O-caffeoate, whose structural formulas are shown in formula I, formula II, formula III and formula IV respectively,

It is characterized in that, the preparation method of this class of hydroxycinnamoyl ester catechins comprises the following steps: S1. Using epicatechin, namely EC, as a raw material, 5, 7, 3' is prepared through four reactions of peracetylation, removal of the acetyl group on the phenolic hydroxyl group, silylation of the phenolic hydroxyl group and removal of the 3-position acetyl group, 4'-O-tetra-tert-butyldimethylsilyl-epicatechin; Using epigallocatechin (EGC) as raw material, 5,7,3',4 is prepared by four reactions: peracetylation, removal of acetyl group on phenolic hydroxyl group, silylation of phenolic hydroxyl group and removal of 3-position acetyl group. ',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin; S2, prepare 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate; Weigh 92.0 mg of 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin prepared in step S1 into a 25 mL round-bottomed flask, add 0.2 mL of dry pyridine, 2.0 mL of dry dichloromethane, 3.0 mL of dry dichloromethane containing 0.18 mmol of 3,4-O-diacetylated caffeoyl chloride was slowly added dropwise in an ice bath, react overnight at room temperature, add an appropriate amount of water and an equal volume of Dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted with petroleum ether:ethyl acetate=30:1 by silica gel column chromatography to obtain 3",4"-O-diacetyl base-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin transcaffeate; S3. Preparation of 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate; Weigh 395.0 mg of 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin prepared in step S1 into a 25 mL round-bottomed flask, add 1.5 mL of dry pyridine, 3.0 mL of dry dichloromethane, slowly dropwise add 5.0 mL of dry dichloromethane containing 0.80 mmol of 4-O-acetyl coumaroyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane Extracted with methane three times, the dichloromethane layer was dried with anhydrous sodium sulfate and then concentrated, subjected to silica gel column chromatography, eluted with petroleum ether:ethyl acetate=50:1 to obtain 4"-O-acetyl-5,7 ,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate; S4. Preparation of 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate ; Weigh 500.0 mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, slowly dropwise add 8.0 mL of dry dichloromethane containing 1.9 mmol of 3,4-O-diacetylated caffeoyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and extracted three times with an equal volume of dichloromethane, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 30:1 to obtain 3", 4"- O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcaffeate; S5, prepare 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate; Weigh 370.0 mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100 mL round-bottomed flask, add 2.0 mL of dry pyridine, 5.0 mL of dry dichloromethane, slowly dropwise add 7.0 mL of dry dichloromethane containing 1.5 mmol of 4-O-acetyl coumaroyl chloride under ice bath conditions, react overnight at room temperature, add an appropriate amount of water and etc. The volume of dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 50:1 to obtain 4"-O-acetyl- 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin transcoumarate; S6, preparation of epicatechin transcaffeate; Weigh 164.0mg of the 3",4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans coffee prepared in step S2 In a 25mL round-bottomed flask, add 28.0mg potassium hydrogen fluoride, then add 6.0mL dry methanol, and react at 50°C for 6 hours. The reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the Catechin transcaffeate; S7, preparing epigallocatechin transcaffeate; Weigh 60.0mg of the 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin obtained in step S4 In a 25 mL round-bottomed flask, 200.0 mg of potassium hydrogen fluoride was added, followed by 5.0 mL of dry methanol, and the reaction was carried out at 50°C for 6 hours. The reaction product was subjected to LH-20 gel column chromatography, washed with methanol. After taking off, epigallocatechin transcaffeate is obtained; S8, prepare epicatechin trans-coumarate; Weigh 163.0 mg of 4"-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-coumarate prepared in step S3 to In a 25mL round-bottomed flask, add 136.0mg of potassium hydrogen fluoride, then add 6.0mL of dry methanol, and react at room temperature for 3.5 hours. After the reaction is completed, add an appropriate amount of water and extract three times with an equal volume of ethyl acetate. The ethyl acetate layer After drying with anhydrous sodium sulfate, it was concentrated, and eluted by silica gel column chromatography with petroleum ether:ethyl acetate=1:1 to obtain 4"-O-acetyl-epicatechin trans-coumarate; Weigh 50.0 mg of 4"-O-acetyl-epicatechin trans-coumarate into a 10 mL round-bottomed flask, add 450.0 mg ammonium acetate, add 2.0 mL of 80% methanol aqueous solution, and react at room temperature for 5.5 After 1 hour, the reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain epicatechin trans-coumarate; S9, prepare epigallocatechin trans-coumarate; Weigh 130.0 mg of the 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-fragrance prepared in step S5. In a 25mL round-bottomed flask, 476.0mg potassium hydrogen fluoride was added, and then 8.0mL of dry methanol was added, and the reaction was carried out at 50°C for 6 hours. The reaction product was concentrated and subjected to LH-20 gel column chromatography, eluting with methanol. After obtaining 4 "-O-acetyl-epigallocatechin trans-coumarate; Weigh 36.0 mg of 4"-O-acetyl-epigallocatechin trans-coumarate into a 10 mL round-bottomed flask, add 460.0 mg ammonium acetate, add 2.0 mL of 80% methanol aqueous solution, and react at room temperature After 5 hours, the reaction product was subjected to LH-20 gel column chromatography and eluted with methanol to obtain epigallocatechin trans-coumarate; The steps S2, S3, S4, and S5 are in no particular order, and the steps S6, S7, S8, and S9 are in no particular order. 2. the preparation method of a class of hydroxycinnamoyl ester type catechins according to claim 1, is characterized in that, the 3,4-O-diacetylated caffeoyl chloride described in step S2 is obtained by the following way: Weigh 180.1 mg of caffeic acid into a 25 mL round-bottomed flask, add 0.3 mL of dry pyridine and 0.5 mL of acetic anhydride, stir overnight at room temperature under the protection of a drying tube, add water to terminate the reaction, and spin to dryness to obtain acetylated coffee The acid is 3,4-O-diacetylated caffeic acid; transfer the reacted acetylated caffeic acid to a 50 mL round-bottomed flask, add 10 mL of thionyl chloride, and heat under reflux at 90°C for 3 hours to obtain 3,4- O-diacetylated caffeoyl chloride, save for later use. 3. the preparation method of a class of hydroxycinnamoyl ester type catechins according to claim 1, is characterized in that, the 4-O-acetylated coumaroyl chloride described in step S3 is obtained by the following way: Weigh 656.0 mg of coumaric acid into a 25 mL round-bottomed flask, add 0.8 mL of dry pyridine and 1.0 mL of acetic anhydride, stir overnight at room temperature under the protection of a drying tube, add water to terminate the reaction, and evaporate to dryness by rotary evaporation to obtain acetylation Coumaric acid; transfer the reacted acetylated coumaric acid to a 25 mL round-bottomed flask, add 3.0 mL of thionyl chloride, heat under reflux at 90° C. for 3 hours to obtain 4-O-acetylated coumaric acid chloride, and store it for later use . 4. A use of a class of hydroxycinnamoyl ester-type catechins prepared by the preparation method of claim 1 in the preparation of hypoglycemic drugs. 5. the use of a class of hydroxycinnamoyl ester-type catechins prepared by the preparation method according to claim 1 in the preparation of hypoglycemic drugs according to claim 4, characterized in that the hypoglycemic drugs Including oral type and injection type, the oral type includes tablets, capsules, granules, drop pills, and the injection type includes injection solution and mixed solution.

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