Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: a biocatalytic equivalent to the Kolbe–Schmitt reaction?

RSC Advances Pub Date: 2014-01-27 DOI: 10.1039/C3RA47719C

Abstract

The enzyme catalyzed carboxylation of electron-rich phenol derivatives employing recombinant benzoic acid decarboxylases at the expense of bicarbonate as CO2 source is reported. In contrast to the classic Kolbe–Schmitt reaction, the biocatalytic equivalent proceeded in a highly regioselective fashion exclusively at the ortho-position of the phenolic directing group in up to 80% conversion. Several enzymes were identified, which displayed a remarkably broad substrate scope encompassing alkyl, alkoxy, halo and amino-functionalities. Based on the crystal structure and molecular docking simulations, a mechanistic proposal for 2,6-dihydroxybenzoic acid decarboxylase is presented.

Graphical abstract: Regioselective ortho-carboxylation of phenols catalyzed by benzoic acid decarboxylases: a biocatalytic equivalent to the Kolbe–Schmitt reaction
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