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黑曲霉天然脂肪酶对消旋布洛芬对映体拆分的优化

Optimization of enantioselective resolution of racemic ibuprofen by native lipase from Aspergillus niger.

作者信息

de O Carvalho Patrícia, Contesini Fabiano J, Bizaco Renato, Calafatti Silvana Ap, Macedo Gabriela A

机构信息

Curso de Farmácia, Universidade São Francisco, Av. São Francisco de Assis, 218, 12916-900, Bragança Paulista, São Paulo, Brazil.

出版信息

J Ind Microbiol Biotechnol. 2006 Aug;33(8):713-8. doi: 10.1007/s10295-006-0138-8. Epub 2006 May 6.

Abstract

Resolution of (R,S)-ibuprofen (2-(4-isobutylphenyl)propionic acid) enantiomers by esterification reaction with 1-propanol in different organic solvents was studied using native Aspergillus niger lipase. The main variables controlling the process (enzyme concentration and 1-propanol:ibuprofen molar ratio) have been optimized using response surface methodology based on a five-level, two-variable central composite rotatable design, in which the selected objective function was enantioselectivity. This enzyme preparation showed preferentially catalyzes the esterification of R(-)-ibuprofen, and under optimum conditions (7% w/v of enzyme and molar ratio of 2.41:1) the enantiomeric excess of active S(+)-ibuprofen and total conversion values were 79.1 and 48.0%, respectively, and the E-value was 32, after 168 h of reaction in isooctane.

摘要

使用天然黑曲霉脂肪酶研究了在不同有机溶剂中通过与1-丙醇的酯化反应拆分(R,S)-布洛芬(2-(4-异丁基苯基)丙酸)对映体。基于五水平、双变量中心复合旋转设计,采用响应面法优化了控制该过程的主要变量(酶浓度和1-丙醇:布洛芬摩尔比),其中选定的目标函数是对映选择性。这种酶制剂优先催化R(-)-布洛芬的酯化反应,在最佳条件下(酶浓度为7%w/v,摩尔比为2.41:1),在异辛烷中反应168小时后,活性S(+)-布洛芬的对映体过量值和总转化率分别为79.1%和48.0%,E值为32。

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