膜反应器中萘普生甲酯的动态拆分

在碱催化连续原位消旋条件下，利用CRL脂肪酶（Candida rugosa lipase）催化的萘普生甲酯立体选择性水解反应。动态拆分制备（S）－普生。使用硫水硅橡胶膜隔离生物催化拆分反应和碱催化消旋反应，解决了常规动态拆分反应中生物催化剂难以承受原位化学消旋苛刻反应条件的难题。为了利于从水－有机溶剂乳化体系中分离产物和克服产物抑制，将亲水半透膜引入搅拌罐反应器，在该膜反应器中进行动态拆分反应。当转化率超过60％时，产物（S）－萘普生的对映体过量值（eep)仍在96％以上，在反应过程中还发现CRL脂肪酶同工酶的转化。

Dynamic Enzymatic Resolution of Naproxen Methyl Ester in a Membrane Bioreactor

A lipase catalyzed enantioselective hydrolysis process under continuous in situ racemization of substrate by using sodium hydroxide as catalyst was developed for the production of ( S ) naproxen from racemic naproxen methyl ester in an aqueous organic biphase system. By using a tubular silicone rubber membrane in a stirring tank reactor to separate the chemical catalytic racemization and biocatalytic resolution processes, the key problem often associated with conventional dynamic resolution, especially, with chemical in situ racemization incompatibility with the presence of a biocatalyst, has been avoided. In order to overcome the product inhibition and to facilitate the product recovery from the aqueous organic emulsion containing substrate and lipase, a hydrophilic porous semipermeable membrane has been applied in the stirring tank reactor. More than 60% conversion of the racemate with enantiomeric excess of product (ee p) higher than 96% was obtained. In addition, conversion of CRL isoenzymes was found in the process of reaction.