Optimization of a process for the production of (R)-2-hydroxy-4-phenylbutyric acid--an intermediate for inhibitors of angiotensin converting enzyme.

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作者：

E Schmidt，O Ghisalba，D Gygax，G Sedelmeier

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摘要：

(R)-2-Hydroxy-4-phenylbutyric acid, an intermediate in the manufacture of inhibitors of angiotensin converting enzyme, can be produced continuously in an enzyme membrane reactor by enzymatic reduction of its corresponding α-keto acid. d -Lactate dehydrogenase ( d -LDH) from Staphylococcus epidermidis was chosen as the most appropriate enzyme to carry out the NADH-dependent reduction. Formate dehydrogenase (FDH) was used for NADH regeneration. Detailed kinetic measurements and a mathematical model for the coupled enzyme reactions were applied to calculate the optimal conditions for continuous production of the α-hydroxy acid. A mass of 3.1 kg (R)-2-hydroxy-4-phenylbutyric acid was synthesized in a 220 ml enzyme membrane reactor over a period of 4 weeks. A mean space-time-yield of 165 g l 1 d 1 was achieved at low enzyme consumptions of 150 U kg 1 α-hydroxy acid for FDH and d -LDH.

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关键词：

R)-2-HYDROXY-4-PHENYLBUTYRIC ACID ENZYME MEMBRANE REACTOR COENZYME REGENERATION STAPHYLOCOCCUS-EPIDERMIDIS

DOI：

10.1016/0168-1656(92)90040-G

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年份：

1992