Method of synthesizing GHK acetate at low cost

An acetate, low-cost technology, applied in the preparation method of peptides, chemical instruments and methods, organic chemistry, etc., can solve the problems of increased by-products, easy removal, cumbersome operation, etc., to reduce production costs and avoid cumbersome Sexuality, avoiding the effect of by-products

Active Publication Date: 2018-03-09
SHAANXI HUIKANG BIO TECH CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

This method has the following defects: (1) histidine is the most easily racemized amino acid, and in terms of maintaining optical purity, it is better to protect the imidazole group with Boc than to protect it with trityl; (2) protect it with acetyl The side chain amino group of lysine, the generated product Boc-Gly-His(Boc)-Lys(Ac)-OH, when deprotected with trifluoroacetic acid, Boc is easy to take off, and acetyl group is not easy to deprotect in trifluoroacetic acid (3...

Method used

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  • Method of synthesizing GHK acetate at low cost
  • Method of synthesizing GHK acetate at low cost

Examples

Experimental program
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Embodiment 1

[0030] 1. Synthesis of Trt-Gly-OSu

[0031] Add 31.7g (0.1mol) Trt-Gly-OH and 300mL tetrahydrofuran into the reaction flask, stir at room temperature to dissolve and clear, add 13.8g (0.12mol) N-hydroxysuccinimide, stir to dissolve and clear, then add 30.9g ( 0.15mol) N,N'-dicyclohexylcarboimide, after stirring at room temperature for 30 minutes, a large amount of white solids precipitated, continued stirring for 3 hours, TLC showed that the reaction of the raw materials was complete, filtered, and the filtrate was concentrated under reduced pressure at 35°C , to obtain 41.4g Trt-Gly-OSu, yield 100%.

[0032] 2. Synthesis of Trt-Gly-His(Trt)-OH

[0033] Dissolve 41.4g (0.1mol) Trt-Gly-OSu in 300mL N,N-dimethylformamide, add 39.7g (0.1mol) His(Trt)-OH, 12.9g (0.1mol) N,N- Diisopropylethylamine, after stirring at room temperature for 1 hour, TLC showed that the raw materials were completely reacted. Pour the reaction solution into 1.5L water, adjust the pH to 3~4 with citric a...

Embodiment 2

[0042] 1. Synthesis of Trt-Gly-OSu

[0043] Add 95.1g (0.3mol) Trt-Gly-OH and 900mL tetrahydrofuran into the reaction flask, stir at room temperature to dissolve and clear, add 38g (0.33mol) N-hydroxysuccinimide, stir to dissolve and clear, then add 80.3g (0.39 mol) N,N'-dicyclohexylcarboimide, after stirring at room temperature for 30 minutes, a large amount of white solids precipitated, and continued stirring for 3 hours, TLC showed that the raw materials were completely reacted, filtered, and the filtrate was concentrated under reduced pressure at 35°C, 120.4 g of Trt-Gly-OSu were obtained with a yield of 97%.

[0044] 2. Synthesis of Trt-Gly-His(Trt)-OH

[0045] Dissolve 120.4 (0.29mol) Trt-Gly-OSu in 900mL N,N-dimethylformamide, add 127g (0.32mol) His(Trt)-OH, 41g (0.32mol) N,N-diisopropyl Ethylamine, after stirring at room temperature for 1 hour, TLC showed that the raw materials were completely reacted, the reaction solution was poured into 1.5L water, and the pH was ...

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Abstract

The invention discloses a method of synthesizing GHK acetate at low cost. The method includes steps of: 1) performing a reaction to Trt-Gly-OH with N-hydroxysuccinimide to generate Trt-Gly-OSu; 2) performing a reaction with H-His(Trt)-OH to generate Trt-Gly-His(Trt)-OH; 3) performing a reaction with N-hydroxysuccinimide to generate Trt-Gly-His(Trt)-OSu; 4) performing a reaction with Lys(Trt)-OH togenerate Trt-Gly-His(Trt)-Lys(Trt)-OH, and removing protective groups from the Trt-Gly-His(Trt)-Lys(Trt)-OH in acetic acid to generate the GHK acetate. In the method, all the protective groups are triphenylmethyl group, so that optical purity is guaranteed well; deprotection can be directly carried in acetic acid, so that byproducts generated during deprotection of trifluoroacetic acid can be avoided. The GHK acetate is free of reverse phase chromatograph for purification and ion exchange chromatography for remove trifluoroacetic acid, so that production cost is reduced largely and the methodcan be used in large-scale production.

Description

technical field [0001] The invention belongs to the technical field of polypeptide synthesis, and in particular relates to a synthesis method of GHK acetate. Background technique [0002] GHK tripeptide is an active polypeptide containing three amino acids. The amino acid sequence is H-Gly-His-Lys-OH. After years of skin anti-wrinkle research, GHK tripeptide has the functions of tissue repair, anti-aging, and wrinkle removal. The complex GHK-Cu formed with copper was first used in medicine to heal wounds and increase skin elasticity. Therefore, it is recommended by dermatologists and plastic surgeons as the most non-irritating anti-aging and anti-wrinkle product in the 21st century. [0003] The Chinese invention patent application with the application number 201310751827.1 discloses a method for preparing GHK, which specifically uses Boc-protected glycine, imidazole group protected by Boc-protected histidine and acetyl-protected side chain amino lysine as Raw materials, s...

Claims

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Application Information

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IPC IPC(8): C07K5/083C07K1/107
CPCC07K5/0806Y02P20/55
Inventor 王惠嘉李晨陈科张忠旗郭添王慧杨小琳赵金礼
Owner SHAANXI HUIKANG BIO TECH CO LTD
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