Lewin Ross, Goodall Mark, Thompson Mark L, Leigh James, Breuer Michael, Baldenius Kai, Micklefield Jason
School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7ND (UK).
Chemistry. 2015 Apr 20;21(17):6557-63. doi: 10.1002/chem.201406014. Epub 2015 Mar 12.
The enzyme aryl/alkenyl malonate decarboxylase (AMDase) catalyses the enantioselective decarboxylative protonation (EDP) of a range of disubstituted malonic acids to give homochiral carboxylic acids that are valuable synthetic intermediates. AMDase exhibits a number of advantages over the non-enzymatic EDP methods developed to date including higher enantioselectivity and more environmentally benign reaction conditions. In this report, AMDase and engineered variants have been used to produce a range of enantioenriched heteroaromatic α-hydroxycarboxylic acids, including pharmaceutical precursors, from readily accessible α-hydroxymalonates. The enzymatic method described here represents an improvement upon existing synthetic chemistry methods that have been used to produce similar compounds. The relationship between the structural features of these new substrates and the kinetics associated with their enzymatic decarboxylation is explored, which offers further insight into the mechanism of AMDase.
芳基/烯基丙二酸脱羧酶（AMDase）可催化一系列二取代丙二酸的对映选择性脱羧质子化反应（EDP），生成手性纯的羧酸，这些羧酸是有价值的合成中间体。与迄今已开发的非酶促EDP方法相比，AMDase具有许多优势，包括更高的对映选择性和更环保的反应条件。在本报告中，AMDase及其工程变体已被用于从易于获得的α-羟基丙二酸酯制备一系列对映体富集的杂芳族α-羟基羧酸，包括药物前体。本文所述的酶法是对用于生产类似化合物的现有合成化学方法的改进。研究了这些新底物的结构特征与其酶促脱羧动力学之间的关系，这为深入了解AMDase的作用机制提供了进一步的见解。
