Miwon Co., Ltd.

Dae K Joo

Min S Han

Bun Sam Lim

E Nam Hwang

Hong K Choi

Kyung Soon Choi

Il Hyun

Kwang H Kim

This invention relates to an improvement in a method for manufacturing dipeptides by coupling N-blocked aspartic acid and a phenylalanine lower alkyl ester in a medium containing a water-miscible organic solvent mixture in the presence of an immobilized metallo-protease so that a continuous reaction is established with stable enzyme activity.

Process for preparing dipeptides

A process for the preparation of .alpha.-L-aspartyl-L-phenylalanine methyl ester in high yield, which comprises the steps of esterifying L-phenylalanine with methanol while undergoing continuous evaporation to remove the water formed during esterification, coupling the produced L-phenylalanine methyl ester with N-formyl-L-aspartic anhydride, deformylating the produced N-formyl-L-aspartyl-L-phenylalanine methyl ester, crystallizing the formed .alpha.-L-aspartyl-L-phenylalanine methyl ester as .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloric acid salt, recovering the first .alpha.-L-aspartyl-L-phenylalanine methyl ester hydrochloric acid salt, esterifying .alpha.-L-aspartyl-L-phenylalanine in the filtrate to produce the second .alpha.-L-aspartyl-L-phenylalanine methyl ester, and combining the first and second .alpha.-L-aspartyl-L-phenylalanine methyl ester product.

Process for producing .alpha.-L-aspartyl-L-phenylalanine methyl ester

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Seoul, South Korea

Dae K Joo