Method of synthesizing GHK acetate at low cost

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...

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) Since the Boc and acetyl groups have no UV absorption, the intermediates in each step cannot be detected by thin-layer chromatography, and liquid phase tracking detection is required, resulting in cumbersome operations (4) after the final deprotection is the trifluoroacetate of GHK, it needs to be purified by reverse chromatography, and further removes trifluoroacetic acid, and can become acetate through ion exchange chromatography, and the cost is too high to be mass-produced

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