CN111233810B - Preparation method and application of hydroxycinnamoyl ester type catechin - Google Patents

Abstract

The invention relates to a preparation method and application of hydroxycinnamoyl ester type catechin. The hydroxycinnamoyl catechin includes 4 kinds of catechins named as epicatechin trans-coumarate, epicatechin trans-caffeate, epigallocatechin trans-coumarate and epigallocatechin trans-caffeate, respectively. The 4 hydroxycinnamoyl ester catechins are prepared by performing four steps of total acetylation, acetyl removal on phenolic hydroxyl, phenolic hydroxyl silanization and 3-bit acetyl removal on epicatechin and epigallocatechin, and then respectively performing esterification and protective group removal on the epicatechin and the epigallocatechin and acetyl chloride of acetylated caffeic acid or coumaric acid. The 4 hydroxycinnamoyl ester type catechins have certain inhibiting effect on alpha-glucosidase activity, can be used for hypoglycemic drugs, and have important significance in the fields of agriculture and medicine.

Description

Preparation method and application of a class of hydroxycinnamoyl catechins

technical field

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

Background technique

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

Chemical synthesis experiments usually require special reaction conditions, and the pharmaceutical reagents used in the reaction are usually more 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 general laboratories cannot meet the reaction requirements, and the preparation cannot be completed. How to screen the existing preparation methods and reaction materials, and design a preparation method of the four hydroxycinnamoyl catechins with simple methods and mild conditions is of great significance.

Contents 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 catechins.

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

In order to solve the technical problems of the present invention, the technical solution provided is:

A method for preparing a class of hydroxycinnamoyl ester catechins. The hydroxycinnamoyl ester catechins include 4 kinds of catechins, and the names of the 4 kinds of catechins are respectively epicatechin trans-coumaric acid Ester (–)-epicatechin 3-O-p-coumaroate, Epigallocatechin trans-coumarate (–)-epigallocatechin3 -O-p-coumaroate, epigallocatechin trans-caffeoate (–)-epigallocatechin3-O-caffeoate, the structural formulas are shown in formula Ⅰ, formula Ⅱ, formula Ⅲ and formula Ⅳ respectively,

The preparation method of the hydroxycinnamoyl ester type catechin comprises the following steps:

S1. Using epicatechin (EC) as a raw material, 5,7,3', 4'-O-tetra-tert-butyldimethylsilyl-epicatechin;

Using epigallocatechin (EGC) as a raw material, 5,7,3',4 is prepared by four reactions: full acetylation, 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. Preparation of 3”, 4”-O-diacetyl-5,7,3’,4’-O-tetra-tert-butyldimethylsilyl-epicatechin trans-caffeate;

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

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 bottom flask, add 1.5 mL of dry pyridine, 3.0 mL of dry dichloromethane, slowly add 5.0 mL of dry dichloromethane containing 0.80 mmol of 4-O-acetylated coumaryl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and an equal volume of dichloromethane Methane was extracted three times, the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated, and silica gel column chromatography was 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 trans-caffeate ;

Weigh 500.0mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100mL round bottom flask, add 2.0mL to dry Pyridine, 5.0 mL of dry dichloromethane, slowly add 8.0 mL of dry dichloromethane containing 1.9 mmol of 3,4-O-diacetylated caffeoyl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and an equal volume of dichloromethane for three extractions, the dichloromethane layer was dried over 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-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-caffeate;

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

Weigh 370.0mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100mL round bottom flask, add 2.0mL to dry Pyridine, 5.0 mL of dry dichloromethane, slowly add 7.0 mL of dry dichloromethane containing 1.5 mmol of 4-O-acetylated coumaryl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and etc. The volume of dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and then concentrated, and 4”-O-acetyl- 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate;

S6, preparing epicatechin trans-caffeate;

Weigh 164.0 mg of 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 bifluoride, then add 6.0mL dry methanol, and react at 50°C for 6 hours. The reaction product is eluted with methanol to obtain the following table: Catechin trans caffeate;

S7, preparing epigallocatechin trans-caffeate;

Weigh 60.0 mg of 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S4 Add 200.0mg of potassium bifluoride to a 25mL round bottom flask, then add 5.0mL of dry methanol, and react at 50°C for 6 hours. The reaction product is subjected to LH-20 gel column chromatography and washed with methanol. After taking off, epigallocatechin trans-caffeate is obtained;

S8, preparing 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 in In a 25mL round bottom flask, add 136.0mg potassium bifluoride, then add 6.0mL dry methanol, react at room temperature for 3.5 hours, add an appropriate amount of water after the reaction is completed, extract three times with an equal volume of ethyl acetate, and the ethyl acetate layer After drying with anhydrous sodium sulfate and concentrating, 4"-O-acetyl-epicatechin trans-coumarate was obtained after silica gel column chromatography was eluted with petroleum ether: ethyl acetate = 1:1;

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

S9, preparing epigallocatechin trans-coumarate;

Weigh 130.0 mg of 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-aroma prepared in step S5 Add 476.0mg of potassium fluoride to a 25mL round-bottomed flask, then add 8.0mL of dry methanol, and react at 50°C for 6 hours. The reaction product is concentrated and eluted with methanol through LH-20 gel column chromatography Finally, 4"-O-acetyl-epigallocatechin trans-coumarate was obtained;

Weigh 36.0mg of 4”-O-acetyl-epigallocatechin trans-coumarate into a 10mL round bottom flask, add 460.0mg of ammonium acetate, add 2.0mL 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 bottom 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 finished, add water to terminate the reaction, and then 3,4-O-diacetylated caffeic acid can be obtained after rotary evaporation to dryness; transfer the reacted acetylated caffeic acid to a 50mL round bottom flask , add 10 mL of thionyl chloride, and heat to reflux at 90°C for 3 hours to obtain crude 3,4-O-diacetylated caffeoyl chloride, which is stored for future use.

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

Weigh 656.0 mg of coumaric acid into a 25 mL round bottom 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 is finished, add water to terminate the reaction, and then obtain acetylated coumaric acid after rotary evaporation; transfer the reacted acetylated coumaric acid to a 25mL round-bottomed flask, add 3.0mL of thionyl chloride, and dissolve at 90 The crude product 4-O-acetylated coumaroyl chloride can be obtained by heating at reflux at ℃ for 3 hours, which is stored for future 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-mentioned 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 and injection types, and the oral types include tablets, capsules, granules, drops, etc. Pills, the injection type includes injection and suspension.

The beneficial effect of the present invention compared with prior art is:

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

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

Description of drawings

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

The meanings of the marks 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 coumaryl chloride

6a, 3”, 4”-O-diacetyl-5,7,3’,4’-O-tetra-tert-butyldimethylsilyl-epicatechin trans-caffeate

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 trans-caffeate

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

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

7b, 4”-O-acetyl-epigallocatechin trans-coumarate

8a, epicatechin trans caffeate

8b, epicatechin trans-coumarate

8c, epigallocatechin trans caffeate

8d. Epigallocatechin trans-coumarate

Detailed ways

The present invention will be further described below in conjunction with embodiment:

This section generally describes the materials and experimental methods used in the experiments of the present invention. While many of the materials and manipulations which are employed for the purposes of the invention are well known in the art, the invention has been described here in as much detail as possible. It will be clear to those skilled in the art that in the following, unless otherwise specified, the materials, equipment and operation methods used in the present invention are well known in the art.

Example 1

Epigallocatechin transcoumarate, epicatechin transcaffeate, epigallocatechin transcoumarate and epigallocatechin transcaffeate hydroxycinnamoyl ester type The preparation of tea;

1.1 Instruments and reagents

¹ H nuclear magnetic resonance spectrum adopts Agilent DD2600 MHz nuclear magnetic resonance instrument; mass spectrometry adopts Agilent6465UPLC-Q-TOF-MS.

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

1.2 Epicatechin trans-coumarate, epicatechin trans-caffeate, epigallocatechin trans-coumarate and epicatechin trans-caffeate hydroxycinnamoyl esters The synthetic route of tea element is as shown in Figure 1;

1.3 Specific implementation methods:

Synthesis of compound 1a:

Weigh 1.16g (4.0mmol) of epicatechin (EC) into a 50mL round bottom flask, add 6.0mL of dry pyridine and 8.0mL of acetic anhydride (84.6mmol), 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 the EC peracetylated product 3,5,7,3',4'-O-pentaacetyl-epicatechin (1a, 1.9g , white powder, yield 95%). ¹ H NMR (600MHz, CDCl ₃ ): 7.33 (1H, s), 7.25 (1H, d, J = 8.4Hz), 7.18 (1H, d, J = 8.4Hz), 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 1.2g (3.9mmol) of epigallocatechin (EGC) into a 50mL round bottom flask, add 6.0mL of dry pyridine, 10.0mL of acetic anhydride (105.7mmol), and stir overnight at room temperature under the protection of a drying tube. After the reaction is finished, add water to terminate the reaction, and after rotary evaporation to dryness, the EGC peracetylated product can be obtained: 3,5,7,3',4',5'-O-hexaacetyl-epigallocatechin (1b, 2.1g, white powder, yield 94%). 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, 4.2Hz), 2.88 (1H, br d, J = 17.4Hz), 2.25-2.28 (15H, m), 1.92 (3H, s).

Synthesis of compound 2a:

Weigh 500.0mg (1.0mmol) of compound 1a into a 100mL round bottom flask, add 50mL of 80% methanol aqueous solution, 7.8g (101.2mmol) of ammonium acetate, and stir overnight at room temperature. After the reaction is finished, add an appropriate amount of water, remove methanol by rotary concentration, extract three times with an equal volume of ethyl acetate, concentrate the ethyl acetate layer, and wash with ethyl acetate:methanol=20:1 through silica gel column chromatography. Compound 3-O-acetyl-epicatechin (2a, 259.0 mg, white powder, yield 78%) was obtained after removal. 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, 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, 4.2Hz), 2.58 (1H, br d, J = 16.8Hz), 1.87 (3H, s).

Synthesis of compound 2b:

Weigh 4.2g (1.0mol) of compound 1b into a 500mL round bottom flask, add 80mL of 80% methanol aqueous solution, 1.0g (11.9mmol) of sodium bicarbonate, and 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 ethyl acetate, the ethyl acetate layer was concentrated, and subjected to silica gel column chromatography, eluted with ethyl acetate:methanol=1:1 to obtain compound 3- O-acetyl-epigallocatechin (2b, 1.05 mg, white powder, yield 40%). 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 200.0mg (0.6mmol) of compound 2a in a 100mL round-bottomed flask, add 10mL of dry dichloromethane, 816.0mg (12.0mmol) of imidazole, 40mg (0.33mmol) of 4-dimethylaminopyridine, under ice-bath conditions 10 mL of a dry dichloromethane solution containing 723.4 mg (4.8 mmol) of tert-butyldimethylchlorosilane was slowly added dropwise. Stir overnight at room temperature. After the reaction is finished, add an appropriate amount of water, extract three times with an equal volume of dichloromethane, wash the dichloromethane layer solution with saturated sodium chloride, concentrate, and perform silica gel column chromatography with petroleum ether:ethyl acetate=100: 1 was eluted to obtain the compound 3-O-acetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin (3a, 450.0 mg, transparent oil, yield 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 500.0mg (1.4mmol) of compound 2b into a 100mL round-bottom flask, add 10mL of dry dichloromethane, 2.4g (35.3mmol) of imidazole, 100mg (0.82mmol) of 4-dimethylaminopyridine, under ice-bath conditions 10 mL of a dry dichloromethane solution containing 2.4 g (16.0 mmol) of tert-butyldimethylchlorosilane was slowly added dropwise. Stir overnight at room temperature. After the reaction is finished, add an appropriate amount of water, extract three times with an equal volume of dichloromethane, wash the dichloromethane layer solution with saturated sodium chloride, concentrate, and perform silica gel column chromatography with petroleum ether:ethyl acetate=200: 1 was eluted to obtain the compound 3-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin (3b, 970.0mg, Transparent oil, yield 74%). ¹ HNMR (600MHz, 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 100.0mg (0.13mmol) of compound 3a into a 50mL round bottom flask, dissolve it in 100uL of dry dichloromethane, then add 10mL of dry methanol, 50.0mg (0.36mmol) of potassium carbonate, and stir at room temperature for 2 hours. After the reaction is finished, add an appropriate amount of water, extract three times with an equal volume of ethyl acetate, dry the ethyl acetate layer solution with anhydrous sodium sulfate and concentrate, and perform 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 (600MHz, CDCl ₃ ): 6.94 (1H, d, J = 1.8Hz), 6.92 (1H, dd, J = 8.4, 1.8Hz), 6.84 (1H, d, J = 7.8Hz), 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 970.0mg (1.06mmol) of compound 3b into a 100mL round bottom flask, dissolve it with 100uL of dry dichloromethane, then add 40mL of dry methanol, 200mg (1.44mmol) of potassium carbonate, and stir at room temperature for 2 hours. After the reaction is finished, add an appropriate amount of water, extract three times with an equal volume of ethyl acetate, dry the ethyl acetate layer solution with anhydrous sodium sulfate and concentrate, and perform silica gel column chromatography with petroleum ether:ethyl acetate=200: 1 was eluted to obtain compound 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin (4b, 353.0 mg, transparent oil, yield 38% ). ¹ H NMR (600MHz, CDCl ₃ ): 6.59 (2H, s), 6.09 (1H, d, J = 1.8Hz), 5.95 (1H, d, J = 2.4Hz), 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 bottom flask, add 0.3 mL of dry pyridine and 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 to dryness. ¹ H NMR (600MHz, 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). Transfer the reacted acetylated caffeic acid to a 50 mL round bottom flask, add 10 mL of thionyl chloride, and heat to reflux at 90° C. for 3 hours to obtain the crude compound 3,4-O-diacetylated caffeoyl chloride (5a), directly for the next reaction.

Synthesis of compound 5b:

Weigh 656.0 mg (4.0 mmol) of caffeic acid into a 25 mL round bottom flask, add 0.8 mL of dry pyridine and 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 to dryness. 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), 7.18 (2H, d, J = 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 bottom flask, 3.0 mL of thionyl chloride was added, and heated to reflux at 90° C. for 3 hours to obtain the crude compound 4-O-acetylated coumaric acid Soybean acid chloride (5b) was directly used in the next reaction.

Synthesis of compound 6a:

Weigh compound 4a (92.0mg, 0.12mmol) in a 25mL round bottom flask, add 0.2mL of dry pyridine, 2.0mL of dry dichloromethane, slowly add dropwise the dry solution containing compound 5a (0.18mmol) under ice bath conditions Dichloromethane 3.0 mL. React overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane to extract three times, the dichloromethane layer is dried over anhydrous sodium sulfate, concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 30:1 The compound 3", 4"-O-diacetyl-5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-caffeate (6a, 95.5 mg, oily, yield 78%). ¹ H NMR (600MHz, CDCl ₃ ): 7.45 (1H, d, J = 15.6Hz), 7.32 (1H, dd, J = 8.4, 1.2Hz), 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 (395.0mg, 0.53mmol) in a 25mL round bottom flask, add 1.5mL of dry pyridine, 3.0mL of dry dichloromethane, slowly add dropwise the dry solution containing compound 5b (0.80mmol) under ice bath conditions Dichloromethane 5.0 mL. React overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane to extract three times, the dichloromethane layer was dried over anhydrous sodium sulfate, concentrated, and subjected to silica gel column chromatography, 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, 197.8mg, Oily, yield 40%). ¹ H NMR (600MHz, CDCl ₃ ): 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, 4.2Hz), 2.90 (1H, dd, J = 16.8, 3.0Hz), 2.28 (3H, s), 0.92-0.97 (36H, m), 0.12-0.21 (24H, m).

Synthesis of compound 6c:

Weigh compound 4b (500.0mg, 0.57mmol) in a 100mL round bottom flask, add 2.0mL of dry pyridine, 5.0mL of dry dichloromethane, slowly add dropwise the dry solution containing compound 5a (1.9mmol) under ice bath conditions Dichloromethane 8.0 mL. React overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane to extract three times, the dichloromethane layer is dried over anhydrous sodium sulfate, concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 30:1 Compound 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-caffeate (6c, 172.1 mg, oil, yield 70%). ¹ H NMR (600MHz, CDCl ₃ ): 7.44(1H,d,J=16.2Hz),7.29(1H,dd,J=8.4,1.8Hz),7.24(1H,s),7.16(1H,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 (370.0mg, 0.42mmol) in a 100mL round bottom flask, add 2.0mL of dry pyridine, 5.0mL of dry dichloromethane, slowly add dropwise the dry solution containing compound 5b (1.5mmol) under ice bath conditions Dichloromethane 7.0 mL. React overnight at room temperature, add an appropriate amount of water and an equal volume of dichloromethane to extract three times, the dichloromethane layer is dried over anhydrous sodium sulfate, concentrated, and eluted by silica gel column chromatography with petroleum ether: ethyl acetate = 50:1 The compound 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate (6d, 280.0 mg, oil, yield 62%). ¹ H NMR (600MHz, 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:

Weigh compound 6b (163.0 mg, 0.17 mmol) into a 25 mL round bottom flask, add potassium bifluoride (136.0 mg, 1.7 mmol), then add 6.0 mL of dry methanol, and react at room temperature for 3.5 hours. After the reaction was completed, an appropriate amount of water was added, and extracted three times with an equal volume of ethyl acetate. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated, and eluted with petroleum ether: ethyl acetate = 1:1 through silica gel column chromatography to obtain compound 4"-O-acetyl-epicatechin trans-aroma Soyate (7a, 70.9mg, white powder, yield 85%). ¹ H NMR (600MHz, 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=16.8Hz), 2.27(3H,s).

Compound 7b synthesis:

Weigh compound 6d (130.0mg, 0.12mmol) into a 25mL round bottom flask, add potassium bifluoride (476.0mg, 6.1mmol), then add 8.0mL dry methanol, and react at 50°C for 6 hours. After the reaction product was concentrated, it was subjected to LH-20 gel column chromatography and eluted with methanol to obtain the compound 4"-O-acetyl-epigallocatechin trans-coumarate (7b, 36.0mg, white powder, yield 60% yield). ¹ H NMR (600MHz, DMSO-d ₆ ): 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).

Synthesis of compound 8a:

Weigh 6a (164.0 mg, 0.16 mmol) into a 25 mL round bottom flask, add potassium bifluoride (28.0 mg, 1.64 mmol), 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 trans-caffeate (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 , 4.8 Hz), 2.67 (1H, br d, J = 16.2 Hz). 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 bottom 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,brd,J=16.2Hz). 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 bifluoride (200.0 mg, 2.56 mmol), 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 trans-caffeate (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 = 2.4Hz), 5.28 (1H, br s), 4.93 (1H, s), 2.90 (1H, dd, J = 17.4, 4.8Hz), 2.64 (1H, br d, J = 16.2Hz). 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 bottom 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 (600MHz, DMSO-d ₆ ): 7.49 (2H, d, J = 8.4Hz), 7.41 (1H, d, J = 15.6Hz), 6.75 (2H, d, J = 8.4Hz), 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, 4.8Hz), 2.65 (1H, br d, J = 16.2Hz). HR-ESI-MS (negative ion): m/z 467.0979[MH] ^- .

Example 2

The epicatechin trans-coumarate, epicatechin trans-caffeate, epigallocatechin trans-coumarate and epigallocatechin trans-caffeate prepared in Example 1 Four hydroxycinnamoyl catechins were tested for their inhibition of α-glucosidase activity in vitro.

2.1 Experimental materials and reagents

Acarbose, potassium phosphate buffer (PPBS, 10mM, pH 6.9), α-glucosidase (0.1U·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 a 96-well plate, add 60 μL of four hydroxycinnamoyl ester catechins with different concentration gradients, and pre-incubate at 37°C for 10 minutes, add 60 μL of pNPG solution respectively, and continue to After incubating at 37°C for 20 minutes, place it in a microplate reader (25°C), and record the A value of the reaction solution under visible light with a wavelength of 405nm. All samples were repeated 3 times, which were recorded as A samples. Replace α-glucosidase with 60 μL of PPBS, record it as A blank (repeat 3 times), and make blank zero adjustment. Replace the sample solution with 60 μL of PPBS, denoted as A test. Replace the sample solution and α-glucosidase with 120 μL of PPBS, and record it as control A (repeat 3 times).

The enzyme inhibition rate to 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 four hydroxycinnamoyl catechins interacting with α-glucosidase could be calculated according to the inhibition curve. The measured results are shown in the table below:

Note: positive control drug - acarbose

As can be seen from the results in the table, four kinds of hydroxycinnamoyl ester type catechins prepared by the present invention: epicatechin trans coumarate, epicatechin trans caffeate, epigallocatechin trans Both coumarate and epigallocatechin trans-caffeate have a strong inhibitory effect 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 implementations described herein are for illustration only, and are not intended to limit the present invention, and those skilled in the art can make various modifications or changes based on it, and within the spirit and principles of the present invention, any Modifications, equivalent replacements, improvements, etc., should all be included within the protection scope of the present invention.

Claims (3)

1. The preparation method of a class of hydroxycinnamoyl ester catechins, the hydroxycinnamoyl ester catechins include 4 kinds of catechins, the names of these 4 kinds of catechins are respectively epicatechin trans-flavored Soyate is (–)-epicatechin 3-O-p-coumaroate, epicatechin trans-caffeoate is (–)-epicatechin3-O-caffeoate, epigallocatechin trans-coumarate is (–) - epigallocatechin 3-O-p-coumaroate, epigallocatechin trans-caffeate (–)-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 the hydroxycinnamoyl catechins comprises the following steps: S1. Using epicatechin (EC) as a raw material, 5,7,3', 4'-O-tetra-tert-butyldimethylsilyl-epicatechin; Using epigallocatechin (EGC) as a raw material, 5,7,3',4 is prepared by four reactions: full acetylation, 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. Preparation of 3”, 4”-O-diacetyl-5,7,3’,4’-O-tetra-tert-butyldimethylsilyl-epicatechin trans-caffeate; Weigh 92.0 mg of 5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin prepared in step S1 into a 25 mL round bottom flask, add 0.2 mL of dry pyridine, 2.0 mL of dry dichloromethane, slowly add 3.0 mL of dry dichloromethane containing 0.18 mmol of 3,4-O-diacetylated caffeoyl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and an equal volume of Dichloromethane was extracted three times, and the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated. After silica gel column chromatography was eluted with petroleum ether: ethyl acetate = 30:1 to obtain 3”, 4”-O-diacetyl -5,7,3',4'-O-tetra-tert-butyldimethylsilyl-epicatechin trans-caffeate; 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 bottom flask, add 1.5 mL of dry pyridine, 3.0 mL of dry dichloromethane, slowly add 5.0 mL of dry dichloromethane containing 0.80 mmol of 4-O-acetylated coumaryl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and an equal volume of dichloromethane Methane was extracted three times, the dichloromethane layer was dried over anhydrous sodium sulfate and concentrated, and silica gel column chromatography was 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 trans-caffeate ; Weigh 500.0mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100mL round bottom flask, add 2.0mL to dry Pyridine, 5.0 mL of dry dichloromethane, slowly add 8.0 mL of dry dichloromethane containing 1.9 mmol of 3,4-O-diacetylated caffeoyl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and an equal volume of dichloromethane for three extractions, the dichloromethane layer was dried over 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-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-caffeate; S5. Preparation of 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate; Weigh 370.0mg of 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S1 into a 100mL round bottom flask, add 2.0mL to dry Pyridine, 5.0 mL of dry dichloromethane, slowly add 7.0 mL of dry dichloromethane containing 1.5 mmol of 4-O-acetylated coumaryl chloride dropwise under ice bath conditions, react overnight at room temperature, add appropriate amount of water and etc. The volume of dichloromethane was extracted three times, the dichloromethane layer was dried with anhydrous sodium sulfate and then concentrated, and 4”-O-acetyl- 5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-coumarate; S6, preparing epicatechin trans-caffeate; Weigh 164.0 mg of 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 bifluoride, then add 6.0mL dry methanol, and react at 50°C for 6 hours. The reaction product is eluted with methanol to obtain the following table: Catechin trans caffeate; S7, preparing epigallocatechin trans-caffeate; Weigh 60.0 mg of 3",4"-O-diacetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin prepared in step S4 Add 200.0mg of potassium bifluoride to a 25mL round bottom flask, then add 5.0mL of dry methanol, and react at 50°C for 6 hours. The reaction product is subjected to LH-20 gel column chromatography and washed with methanol. After taking off, epigallocatechin trans-caffeate is obtained; S8, preparing 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 in In a 25mL round bottom flask, add 136.0mg potassium bifluoride, then add 6.0mL dry methanol, react at room temperature for 3.5 hours, add an appropriate amount of water after the reaction is completed, extract three times with an equal volume of ethyl acetate, and the ethyl acetate layer After drying with anhydrous sodium sulfate and concentrating, 4"-O-acetyl-epicatechin trans-coumarate was obtained after silica gel column chromatography was eluted with petroleum ether: ethyl acetate = 1:1; Weigh 50.0 mg of 4”-O-acetyl-epicatechin trans-coumarate into a 10 mL round bottom flask, add 450.0 mg of ammonium acetate, add 2.0 mL of 80% methanol aqueous solution, and react at room temperature for 5.5 hour, the reaction product was subjected to LH-20 gel column chromatography, and was eluted with methanol to obtain epicatechin trans-coumarate; S9, preparing epigallocatechin trans-coumarate; Weigh 130.0 mg of 4"-O-acetyl-5,7,3',4',5'-O-penta-tert-butyldimethylsilyl-epigallocatechin trans-aroma prepared in step S5 Add 476.0mg of potassium fluoride to a 25mL round-bottomed flask, then add 8.0mL of dry methanol, and react at 50°C for 6 hours. The reaction product is concentrated and eluted with methanol through LH-20 gel column chromatography Finally, 4"-O-acetyl-epigallocatechin trans-coumarate was obtained; Weigh 36.0mg of 4”-O-acetyl-epigallocatechin trans-coumarate into a 10mL round bottom flask, add 460.0mg of ammonium acetate, add 2.0mL 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; Wherein, steps S2, S3, S4, and S5 are in no particular order, and steps S6, S7, S8, and S9 are in no particular order. 2. The preparation method of a class of hydroxycinnamoyl catechins according to claim 1, wherein the 3,4-O-diacetylated caffeoyl chloride described in step S2 is obtained in the following manner: Weigh 180.1 mg of caffeic acid into a 25 mL round bottom 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 obtain acetylated coffee after rotary evaporation The acid is 3,4-O-diacetylated caffeic acid; transfer the reacted acetylated caffeic acid to a 50mL round bottom flask, add 10mL of thionyl chloride, and heat to reflux at 90°C for 3 hours to obtain 3,4- O-diacetylated caffeoyl chloride, kept for future use. 3. the preparation method of a class of hydroxycinnamoyl catechins according to claim 1, is characterized in that, the 4-O-acetylated coumaryl chloride described in step S3 is obtained by the following method: Weigh 656.0mg of coumaric acid into a 25mL round bottom flask, add 0.8mL of dry pyridine and 1.0mL of acetic anhydride, stir overnight at room temperature under the protection of a drying tube, add water to terminate the reaction, and obtain acetylation after rotary evaporation to dryness Coumaric acid: transfer the reacted acetylated coumaric acid to a 25mL round bottom flask, add 3.0mL thionyl chloride, and heat to reflux at 90°C for 3 hours to obtain 4-O-acetylated coumaryl chloride, which is stored for future use .

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