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Enzymatic Enantioselective Decarboxylative Protonation of Heteroaryl Malonates
Author(s) -
Lewin Ross,
Goodall Mark,
Thompson Mark L.,
Leigh James,
Breuer Michael,
Baldenius Kai,
Micklefield Jason
Publication year - 2015
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.201406014
Subject(s) - enantioselective synthesis , malonate , decarboxylation , protonation , chemistry , enzyme , enzyme catalysis , organic chemistry , malonic acid , aryl , combinatorial chemistry , catalysis , stereochemistry , ion , alkyl
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.