Invention Application
WO2002098905A2 ENZYMATIC COUPLING OF L-PHENYLALANINE METHYL ESTER AND N-BENZYLOXYCARBONYL-L-ASPARTIC ACID IN A CONTINUOUS OR FED-BATCH PROCESS
审中-公开
连续或FED-BATCH方法中L-苯乙胺甲酯和N-苄氧羰基-L-十六烷酸的酶联
- Patent Title: ENZYMATIC COUPLING OF L-PHENYLALANINE METHYL ESTER AND N-BENZYLOXYCARBONYL-L-ASPARTIC ACID IN A CONTINUOUS OR FED-BATCH PROCESS
- Patent Title (中): 连续或FED-BATCH方法中L-苯乙胺甲酯和N-苄氧羰基-L-十六烷酸的酶联
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Application No.: PCT/NL2002/000364Application Date: 2002-06-04
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Publication No.: WO2002098905A2Publication Date: 2002-12-12
- Inventor: TOKUDA, Akira , YAMAMOTO, Norihiro , NAKAMURA, Shiichiro , QUAEDFLIEG, Peter, Jan, Leonard, Mario
- Applicant: HOLLAND SWEETENER COMPANY V.O.F. , TOKUDA, Akira , YAMAMOTO, Norihiro , NAKAMURA, Shiichiro , QUAEDFLIEG, Peter, Jan, Leonard, Mario
- Applicant Address: Koestraat 1, NL-6167 RA Geleen NL
- Assignee: HOLLAND SWEETENER COMPANY V.O.F.,TOKUDA, Akira,YAMAMOTO, Norihiro,NAKAMURA, Shiichiro,QUAEDFLIEG, Peter, Jan, Leonard, Mario
- Current Assignee: HOLLAND SWEETENER COMPANY V.O.F.,TOKUDA, Akira,YAMAMOTO, Norihiro,NAKAMURA, Shiichiro,QUAEDFLIEG, Peter, Jan, Leonard, Mario
- Current Assignee Address: Koestraat 1, NL-6167 RA Geleen NL
- Agency: DAUTZENBERG, Jozef, Marie, Andreas
- Priority: EP01202172.1 20010607
- Main IPC: C07K5/06
- IPC: C07K5/06
Abstract:
The invention relates to a process for the preparation of N-benzyloxycarbonyl-α-L-aspartyl-L-phenylalanine methyl ester (Z-APM) by high-conversion enzymatic coupling of N-benzyloxycarbonyl-L-aspartic acid (Z-Asp) and L-phenylalanine methyl ester (L-PM) in a reaction mixture comprising an aqueous medium, a neutral protease as enzyme and an alkali metal salt, alkaline earth metal salt or ammonium salt, with formation of a precipitate. The enzymatic coupling of Z-Asp and L-PM is carried out in a continuous or fed-batch process at a pH of from 5.0 to 6.5 and an average charged molar ratio of Z-Asp and L-PM between 1:1 and 2:1 and wherein the actual molar ratio of Z-Asp and L-PM is higher than the average charge molar ratio. Preferably the alkali metal salt, alkaline earth metal salt or ammonium salt is present in an amount of from 3 to 25 %, calculated as % by weight based on the total reaction mixture.
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