New preparation method of L-alanyl-L-glutamine

Abstract

The invention provides a new preparation method of L-alanyl-L-glutamine. The new preparation method comprises the following steps of: reacting phthalic anhydride with L-alanyl so as to prepare phthalic anhydride-L-alanyl, and acylating and halogenating the phthalic anhydride-L-alanyl with a halogenated reagent so as to synthesize phthalic anhydride-L-alanyl halogen; carrying out esterification reaction on L-glutamic acid and alcohol under the action of acid catalysis to obtain L-glutamic acid monoester; condensing the L-glutamic acid monoester and the phthalic anhydride-L-alanyl halogen under the action of alkali to obtain phthalic anhydride-L-alanyl-L-glutamic acid monoester which is an important intermediate for synthesizing the L-alanyl-L-glutamine; adding the phthalic anhydride-L-alanyl-L-glutamic acid monoester to ammonium hydroxide for ammonolysis and deprotection, and finally crystallizing in alcohol to obtain L-alanyl-L-glutamine. The new preparation method has the advantages that reaction raw materials are easily available, L-glutamic acid and L-alanyl are low in price, the product purity and the product yield are high, the production cost can be effectively reduced, and large-scale production is realized.

Description

technical field [0001] The invention relates to a preparation method of dipeptide, in particular to a preparation method of L-alanyl-L-glutamine. Background technique [0002] L-alanyl-L-glutamine, referred to as proglutide, was developed by Fresenius AG of Germany. It was launched in Germany in 1995 and in China in 1999 under the trade name Lipeptide. Lipeptide has the functions of promoting positive nitrogen balance and regulating muscle protein synthesis. As an important component of parenteral nutrition, it can prevent the increase and atrophy of small intestinal mucosal permeability caused by long-term application of parenteral nutrition, and can enhance immune function and Prevention of bacteremia in patients requiring glutamine supplementation, including those in catabolic and hypermetabolic conditions. In the existing preparation method of L-alanyl-L-glutamine, such as European patent (EP NO 311.057), benzyloxycarboalanine is used to generate active ester in the pre...

AI Technical Summary

Problems solved by technology

As can be seen from the above routes, the various methods for preparing L-alanyl-L-glutamine that have been industrialized at present all use expensive glutamine, resulting in the production of L-alanyl-L-glutamine. -The price of glutamine remains high, so it is inevitable to find cheap new raw materials to replace expensive glutamine

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