Exploring the Catalytic Promiscuity of Phenolic Acid Decarboxylases: Asymmetric, 1,6‐Conjugate Addition of Nucleophiles Across 4‐Hydroxystyrene

Abstract

The catalytic promiscuity of a ferulic acid decarboxylase from <i>Enterobacter</i> sp. (FDC_<i>E</i>s) and phenolic acid decarboxylases (PADs) for the asymmetric conjugate addition of water across the C=C bond of hydroxystyrenes was extended to the N-, C- and S-nucleophiles methoxyamine, cyanide and propanethiol to furnish the corresponding addition products in up to 91% <i>ee</i>. The products obtained from the biotransformation employing the most suitable enzyme/nucleophile pairs were isolated and characterized after optimizing the reaction conditions. Finally, a mechanistic rationale supported by quantum mechanical calculations for the highly (<i>S</i>)-selective addition of cyanide is proposed.