Regioselective Enzymatic β-Carboxylation of para-Hydroxystyrene Derivatives Catalyzed by Phenolic Acid Decarboxylases

We report on a 'green' method for the utilization of carbon dioxide as C-1 unit for the regioselective synthesis of (E)-cinnamic acids via regioselective enzymatic carboxylation of para-hydroxystyrenes. Phenolic acid decarboxylases from bacterial sources catalyzed the beta-carboxylation of para-hydroxystyrene derivatives with excellent regio- and (E/Z)-stereoselectivity by exclusively acting at the beta-carbon atom of the C=C side chain to furnish the corresponding (E)-cinnamic acid derivatives in up to 40% conversion at the expense of bicarbonate as carbon dioxide source. Studies on the substrate scope of this strategy are presented and a catalytic mechanism is proposed based on molecular modelling studies supported by mutagenesis of amino acid residues in the active site.