Preparation method of epigallocatechin gallate derivatives

A technology of epigallocatechin and gallate, applied in the field of compound application, can solve the problems of easy oxidation of hydroxyl group, difficult application, poor ability to penetrate cell membrane, etc.

Active Publication Date: 2018-11-02
许爱娥 +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

The polyhydroxyl structure of EGCG itself makes it unstable in the environment, and the hydroxyl group is easily oxidized, resulting in a decrease in antioxidant capacity
At the same time, EGCG has good water solubility, poor ability to penetrate the cell membrane, and low bioavailability, which brings difficulties to the application.

Method used

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  • Preparation method of epigallocatechin gallate derivatives
  • Preparation method of epigallocatechin gallate derivatives
  • Preparation method of epigallocatechin gallate derivatives

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0016] Synthesis of fully acylated EGCG

[0017]

[0018] 1. Compound A 1 (full acetylation) synthesis:

[0019] 115 mg of Compound 1 (EGCG) was dissolved in ethyl acetate, 200 mg of triethylamine was added, and then 250 mg of acetic anhydride was slowly added dropwise to react overnight. After the reaction is complete, use 10ml of water, 10ml of dilute hydrochloric acid, 10ml of saturated NaHCO 3 Wash the reaction solution 3 times, add anhydrous Na 2 SO 4 After drying, the solvent was recovered under reduced pressure, and recrystallized from ethanol to obtain 192 mg of white solid, yield: 95%.

[0020] 1 H NMR (500MHz, CDCl 3 )δ7.62(s,2H),7.23(s,2H),6.73(d,J=2.2Hz, 1H),6.60(d,J=2.3Hz,1H),5.63(d,J=1.5Hz, 1H), 5.17(s, 1H), 3.02(qd, J=17.9, 3.5Hz, 2H), 2.31–2.22(m, 24H).

[0021] 2. Compound A 2 (full propionylation) synthesis:

[0022] Procedure and Compound A 1 The synthesis is the same, except that acetic anhydride is replaced by propionic anhydride to obtain a ...

Embodiment 2

[0028] Synthesis of Partially Acylated EGCG

[0029]

[0030] Table 1: Conversion rates for the synthesis of partially acylated EGCG

[0031]

[0032]

[0033] The specific implementation process:

[0034] Dissolve 2g EGCG in ethyl acetate, add a certain amount of K 2 CO 3 Solid, then slowly add different equivalents of different acid chlorides (1-6 equivalents) dropwise, after 5 hours of reaction, TLC board monitors new spots, then use 20ml water, 20ml dilute hydrochloric acid, 20ml saturated NaHCO 3 Wash the reaction solution 3 times, anhydrous Na 2 SO 4 Dry, recover the solvent under reduced pressure, pass through a silica gel column, separate out different new spots, and use 1 HNMR normalized conversion.

Embodiment 3

[0036] Synthesis of Different Numbers of Hydroxyls and Different Numbers of Hydroxyl Peracetylation and Perpropionylation Based on EGCG Modification

[0037]

[0038] The specific implementation process:

[0039] 1. Synthesis of compound 4:

[0040] Compound 2 (7.24mmoL), KOH (15.93mmoL), and benzyl bromide (10.86mmoL) were dissolved in ethanol (20mL) and water (2.2mL), and heated to reflux for 20h. Then 20% KOH aqueous solution was added, the mixture was heated to reflux for 4 h, the reaction mixture was cooled, water was added, acidified with 2N hydrochloric acid, filtered with suction, and the obtained solid was recrystallized with ethanol to obtain compound 3, a white solid, with a yield of 70%-80%.

[0041] Compound 3-2 (R 2 =4-OBn): 1 H NMR (400MHz, DMSO) δ12.64(s, 1H), 7.90(d, J=8.8Hz, 2H), 7.40(ddd, J=23.7, 17.2, 7.2Hz, 5H), 7.10(d, J= 8.8Hz,2H), 5.18(s,2H).

[0042] Compound 3-3(R 3 =3,4-diOBn): 1 H NMR (400MHz, CDCl 3 )δ7.55(d, J=7.3Hz, 2H), 7.51–7.29(m, 1...

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PUM

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Abstract

The invention mainly aims at achieving lipid-solubility transformation of epigallocatechin gallate which is polyhydroxy, good in water solubility and low in bioavailability, including three ways, namely encapsulating hydroxyl with different anhydrides so as to reduce the water solubility, carrying out an esterification reaction by virtue of acyl chloride differing in lipid-solubility chain to reduce the water solubility and reducing the number of the hydroxyl. Upon detection, in the obtained epigallocatechin gallate derivatives, a per-acetylated derivative and a per-propionylated derivate are significantly better than an epigallocatechin gallate precursor in the aspect of an effect of preventing and treating leucoderma.

Description

technical field [0001] The invention belongs to the field of compound application, in particular to the application of epigallocatechin gallate derivatives in the treatment of vitiligo. Background technique [0002] Vitiligo is a hypopigmented skin disease characterized clinically by localized or generalized skin depigmentation. Leukoplakia on exposed parts such as the face and neck has caused disfiguring damage to the patient and seriously affected the patient's physical and mental health. Current studies believe that the disease is an autoimmune disease, and the specific killing of melanocytes by CD8+ toxic T lymphocytes is an important reason for the loss of epidermal melanocytes. In addition, there is an increase in the concentration of active oxygen such as hydrogen peroxide locally in the skin lesion area of ​​vitiligo. In addition to the direct killing effect on melanocytes, high concentration hydrogen peroxide can also affect the antigen presentation of melanocytes...

Claims

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Application Information

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Patent Type & Authority Patents(China)
IPC IPC(8): A61K31/353A61P17/00C07D311/62
Inventor 许爱娥王遂泉
Owner 许爱娥
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