Synthesis method of glycyl-L-tyrosine

Abstract

The invention discloses a synthesis method of glycyl-L-tyrosine, and belongs to the technical field of organic synthesis. The method comprises the following steps of by taking glycine as an initial raw material, carrying out amino protection, acylating chlorination, peptide grafting, deprotection and refining to finally obtain high-purity glycyl-L-tyrosine. The method has the advantages of cheap and easily available initial raw materials, mild conditions, high kettle efficiency, simple and controllable impurities and the like, and provides a feasible scheme for process research of the glycyl-L-tyrosine.

Description

technical field [0001] The invention belongs to the technical field of organic synthesis, and specifically discloses a synthesis method of glycyl-L-tyrosine. Background technique [0002] As one of the main components of parenteral nutrition preparation compound amino acid (15) dipeptide (2) injection, glycyl-L-tyrosine is a kind of artificially synthesized dipeptide amino acid, which mainly provides patients with L-tyrosine amino acid, to ensure hyperthyroidism, to promote protein synthesis. Therefore, glycyl-L-tyrosine has a broad development space in the medical field. [0003] The synthetic method of disclosed glycyl-L-tyrosine mainly contains following several kinds at present: [0004] Method 1: U.S. Patent US6197998B1 reports a synthesis scheme using chloroacetyl chloride and L-tyrosine as starting materials, and undergoes acylation, ammonolysis, and purification to obtain glycyl-L-tyrosine. Although the steps of this scheme are relatively short, the price of the s...

AI Technical Summary

Problems solved by technology

Although the steps of this scheme are relatively short, the price of the starting material chloroacetyl chloride is relatively high, a large amount of ammonia water and ammonium carbonate need to be used, the kettle efficiency is very low, the reaction time is too long, and the three industrial wastes are relatively high

[0005] Method 2: European patent EP311057 (1998) reported a method of first making N-succinimide and benzyloxycarbonylglycine into an active ester, then condensing with tyrosine ethyl ester through a condensing agent to form a peptide, and then hydrolyzing to obtain glycine The synthetic scheme of acyltyrosine, the raw material of this scheme is expensive, and the yield is on the low side, unsuitable for industrial production

[0006] Scheme 3: Chinese patent CN103172695B reports a synthesis scheme using glycine and L-tyrosine as starting materials. Glycine is directly reacted with thionyl chloride to prepare glycyl chloride hydrochloride, and then under alkaline conditions Condensation with tyrosine to generate glycyl tyrosine. In this scheme, the amino group of glycine is not protected and the acid chloride is directly prepared. The reaction product is very complicated, resulting in a very low yield of the target product and difficult purification, which cannot be industrialized.

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