生物催化不对称还原制备氟代手性醇

由于氟原子的特殊性质,化合物中引入氟原子可显著改变其物理化学性质。因此,氟原子在药物中的应用越来越广。此外,80%药物分子结构属于手性分子。其中,氟代手性醇常见于手性药物结构中,该类结构的合成方法研究具有重要的意义。不对称还原含氟酮是合成此结构的常见方法。与化学还原方法相比,生物催化还原具有对映选择性强、产率高和易于分离纯化等优点。生物催化,特别是酶催化还原含氟酮类化合物成为手性药物合成领域的研究热点。本文从纯化酶催化和全细胞催化两个方面,综述了近年来含氟酮生物催化还原合成氟代手性醇的研究进展,并分析总结了氟代对酮生物催化还原的影响,最后对生物催化还原法未来的发展进行了展望。

Preparation of Chiral Fluorinated Alcohols by Biocatalytic Asymmetric Reduction

Due to the remarkable properties of fluorine atoms, the physicochemical properties of many molecules can be significantly improved after introducing the fluorine atoms. Therefore, fluorine atom is more and more widely used in pharmaceutical field. In addition, 80% of pharmaceutical compounds are chiral molecules. It should be mentioned that chiral fluorinated alcohols are commonly uslized to bulid chiral pharmacecutical ingredients. Hence, the research exploring the synthesis methods of such structures is of great importance. Asymmetric reduction of fluorinated ketones is a common method for obtaining this structure. Compared with chemical reduction, biocatalytic reduction shows many advantages, such as high enantioselectivity and yield, easy separation and purification. Biocatalysis, especially enzyme-catalyzed reduction of fluorinated ketones, has grown a research hotspot in the field of preparing chiral compounds. At present, biocatalysis methods have some disadvantages. The reaction time is relatively long and the price of biological enzymes and coenzymes is expensive. Accordingly, the scientists should work on shortening the reaction time, recycling biological enzymes and developing more efficient and economical coenzyme regeneration systems. In this paper, the recent development of biocatalytic reduction of fluorine-substituted ketones to fluorinated chiral alcohols is reviewed from the aspects of purified enzyme catalysis and whole-cell catalysis. Moreover, the effect of fluorination on the biocatalytic reduction of ketones is highlighted and the prospect of catalytic reduction method is also put forward in this review.