Enzymatic enantioselective decarboxylative protonation of heteroaryl malonates.

Chemistry : a European Journal
Ross LewinJason Micklefield

Abstract

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.

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Citations

Aug 28, 2016·Applied Microbiology and Biotechnology·Kenji Miyamoto, Robert Kourist
Jan 26, 2016·Angewandte Chemie·Raffael C WendePeter R Schreiner
Apr 21, 2018·ACS Chemical Biology·Qi ZhangEvripidis Gavathiotis
Nov 13, 2020·Journal of the American Chemical Society·Michal BilerShina Caroline Lynn Kamerlin

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