Structure-Guided Directed Evolution of Alkenyl and Arylmalonate Decarboxylases

摘要

The asymmetric decarboxylation of prochiral α-disubstituted malonic acids is an attractive route to produce homochiral α-substituted carboxylic acids. Various metal-catalysed and organocatalytic methods have been explored for related enantioselective decarboxylative protonation (EDP) reactions. However, the synthetic EDP methods can only deliver chiral carboxylic acids or esters with moderate enantioselec-tivities (ee). On the other hand, enzymatic decarboxylation offers a cleaner, more sustainable and more efficient approach to deliver carboxylic acids of very high ee. Notably, the arylmalonate decarboxylase (AMDase) isolated from Bordetella bronchiseptica has been shown to be highly effective in the decarboxylation of α-arylmalonates to give enantiomerically pure α-arylcarboxylic acids (Scheme 1).