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手性拆分酮洛芬对映体为右旋酮洛芬的动力学拆分相关性及生物催化策略。

Relevance and bio-catalytic strategies for the kinetic resolution of ketoprofen towards dexketoprofen.

机构信息

a Centro de Investigación y Desarrollo en Ciencias Aplicadas-Dr. Jorge J. Ronco (CINDECA) , Universidad Nacional de La Plata, CONICET , La Plata , Buenos Aires , Argentina.

出版信息

Crit Rev Biotechnol. 2018 Aug;38(5):778-800. doi: 10.1080/07388551.2017.1399249. Epub 2017 Nov 10.

Abstract

This review presents the most relevant investigations concerning the biocatalytic kinetic resolution of racemic ketoprofen to dexketoprofen for the last 22 years. The advantages related to the administration of the dex-enantiomer in terms of human health, the so called "chiral switch" in the pharmaceutical industry and the sustainability of biotransformations have been the driving forces to develop innovative technology to obtain dexketoprofen. In particular, the kinetic resolution of racemic ketoprofen through enantiomeric esterification and hydrolysis using lipases as biocatalysts are thoroughly revised and commented upon. In this context, the biocatalysts, acyl-acceptors (alcohols), reaction conditions, conversion, enantiomeric excess, and enantiomeric ratio among others are discussed. Moreover, the investigations concerning scaling up processes in order to obtain an optically pure enantiomer of the profen are presented. Finally, some guidelines about perspectives of the technology and research opportunities are given.

摘要

这篇综述介绍了过去 22 年来,关于将外消旋酮洛芬通过生物催化动力学拆分转化为右旋酮洛芬的最相关研究。将右旋异构体用于医疗的优势,即所谓的“手性转换”在制药行业以及生物转化的可持续性,是推动开发创新技术以获得右旋酮洛芬的动力。特别是,使用脂肪酶作为生物催化剂通过对映体酯化和水解来动力学拆分外消旋酮洛芬的方法得到了深入的综述和评论。在这种情况下,讨论了生物催化剂、酰基受体(醇)、反应条件、转化率、对映体过量和对映体比等。此外,还介绍了为获得光学纯对映体而进行的扩大生产过程的研究。最后,给出了关于该技术的前景和研究机会的一些指导方针。

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