基于微生物法甾体羟基化反应

Steroidal Hydroxylation Based on Microbial Method

甾体化合物又称类固醇,是重要的药物活性成分和药物合成中间体,因其具有环戊烷多氢菲的基本骨架,反应类型丰富,其中羟基化反应因产品具有广阔的市场应用前景而受到广泛关注。羟基化反应有化学法和生物法两种,生物法具有区域和立体专一性、对映体专一性等特点而成为目前主要的生产方法。首先从反应原理、类型及机制3个方面介绍了甾体微生物羟基化过程;其次,基于文献及自身研究工作,从甾体羟基化反应的发酵条件、底物溶解性、跨膜运输及反应器内流体力学特性4个角度对羟基化过程的影响进行了综述;最后,基于甾体羟基化反应特性及当前研究进展,对该反应过程后续研究提出展望,旨在为后期甾体羟基化反应的相关研究提供一定参考依据。

Steroids are important active components of drugs and intermediates in drug synthesis.There existed various transformations of steroids because of the basic skeleton of cyclopentane dihydrophenanthrene.Hydroxylation has attracted extensive attention on account of its broad market application prospect.There are two methods to accomplish hydroxylation:chemical method and biological method.Biological method has become the main production method due to its regio specificity,stereos-pecificity and enantiomeric specificity.In this article,firstly,the microbial hydroxylation process of steroids was introduced from three aspects:reaction principle,reaction type and reaction mechanism;secondly,the effect of fermentation conditions,substrate solubility,transmembrane transport and hydrodynamics in the reactor on the hydroxylation process were reviewed based on the research results of the literature and our own work;finally,the prospect was put forward based on the characteristics of the hydroxylation process and the present progress,aiming to provide some reference for the related research on the steroid hydroxylation in the future.