Department of Chemistry, Organic & Bioorganic Chemistry, University of Graz, Heinrichstrasse 28, A-8010 Graz, Austria.
J Org Chem. 2013 Feb 15;78(4):1525-33. doi: 10.1021/jo302484p. Epub 2013 Jan 28.
The asymmetric bioreduction of a library of β-cyanoacrylate esters using ene-reductases was studied with the aim to provide a biocatalytic route to precursors for GABA analogues, such as pregabalin. The stereochemical outcome could be controlled by substrate-engineering through size-variation of the ester moiety and by employing stereochemically pure (E)- or (Z)-isomers, which allowed to access both enantiomers of each product in up to quantitative conversion in enantiomerically pure form. In addition, stereoselectivities and conversions could be improved by mutant variants of OPR1, and the utility of the system was demonstrated by preparative-scale applications.
使用烯还原酶对β-氰基丙烯酸酯库进行不对称生物还原的研究，旨在为 GABA 类似物（如普瑞巴林）的前体提供一种生物催化途径。通过对酯基部分的大小变化和使用立体纯的（E）-或（Z）异构体进行底物工程，可以控制立体化学结果，从而以对映体纯的形式获得每种产物的两种对映异构体，转化率高达定量。此外，通过 OPR1 的突变变体可以提高立体选择性和转化率，该系统的实用性通过制备规模的应用得到了证明。
