title: Enzymatic enantioselective decarboxylative protonation of heteroaryl malonates.
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.
authors.affiliation: School of Chemistry and Manchester Institute of Biotechnology, The University of Manchester, 131 Princess Street, Manchester M1 7ND (UK).
authors.forename: Ross
authors.initials: R
authors.lastname: Lewin
authors.forename: Mark
authors.initials: M
authors.lastname: Goodall
authors.forename: Mark L
authors.initials: ML
authors.lastname: Thompson
authors.forename: James
authors.initials: J
authors.lastname: Leigh
authors.forename: Michael
authors.initials: M
authors.lastname: Breuer
authors.forename: Kai
authors.initials: K
authors.lastname: Baldenius
authors.forename: Jason
authors.initials: J
authors.lastname: Micklefield
mesh_terms: D002262:Carboxy-Lyases / Q000378:metabolism*; D002264:Carboxylic Acids / Q000737:chemistry*; D002384:Catalysis; D003653:Decarboxylation; D008314:Malonates / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D002264:Carboxylic Acids; D008314:Malonates; C030290:malonic acid; D002262:Carboxy-Lyases; C071852:malonate decarboxylase
keywords: biocatalysis; decarboxylase; enzyme mechanism; hydroxycarboxylic acids; synthesis