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[低水-有机双相体系中消旋萘普生的酶法拆分]

[Enzymatic resolution of racemic naproxen in a low aqueous-organic biphase system].

作者信息

Xin J Y, Li S B, Xu Y, Wang L L, Shen R N

机构信息

OSSO, Lanzhou Institute of Chemical Physics, Chinese Academy of Sciences.

出版信息

Sheng Wu Gong Cheng Xue Bao. 2000 Jan;16(1):55-9.

Abstract

A stereoselective hydrolysis of the racemic naproxen methyl ester by immobilized lipase from Candida rugosa in a low aqueous-organic biphase system was studied. Support polar, water content, the logP value of organic phase and product inhibition effected the activity of immobilized enzyme. According to these reaction conditions, a low aqueous-organic biphase system for the continuous production of (S)-(+)-Naproxen was developed. The reaction was carried out in a continuous-flow closed-loop 50 mL stirred bioreactor packed with YWG-C6H5, a poorly polar synthetic support on which the lipase had been immobilized by adsorption. The aqueous phase was permanently remained in the reactor associated with the immobilized enzyme particles; the organic phase containing substrate was pumped through this reactor and emerged with the products. The continous-flow stirred bioreactor containing 75 mg lipase was allowed to operate continuously for 60 days at 30 degrees C with a 25% loss of activity, 900 mg of (S)-(+)-Naproxen (eep 95%) were producted.

摘要

研究了在低水-有机双相体系中,皱褶假丝酵母固定化脂肪酶对外消旋萘普生甲酯的立体选择性水解。载体极性、含水量、有机相的logP值和产物抑制作用影响固定化酶的活性。根据这些反应条件,开发了一种用于连续生产(S)-(+)-萘普生的低水-有机双相体系。反应在装有YWG-C6H5的50 mL连续流闭环搅拌生物反应器中进行,YWG-C6H5是一种极性较弱的合成载体,脂肪酶通过吸附固定在其上。水相永久保留在与固定化酶颗粒相关的反应器中;含有底物的有机相被泵入该反应器,并与产物一起流出。含有75 mg脂肪酶的连续流搅拌生物反应器在30℃下连续运行60天,活性损失25%,生产出900 mg (S)-(+)-萘普生(ee p 95%)。

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