Christiane Wuensch

Regioselective Enzymatic Carboxylation of Phenols and Hydroxystyrene Derivatives

The enzymatic carboxylation of phenol and styrene derivatives using (de)carboxylases in carbonate buffer proceeded in a highly regioselective fashion: Benzoic acid (de)carboxylases selectively formed o-hydroxybenzoic acid derivatives, phenolic acid (de)carboxylases selectively acted at the β-carbon atom of styrenes forming (E)-cinnamic acids.

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

Abstract We report on a ‘green’ method for the utilization of carbon dioxide as C1 unit for the regioselective synthesis of (E)‐cinnamic acids via regioselective enzymatic carboxylation of para‐hydroxystyrenes. Phenolic acid decarboxylases from bacterial sources catalyzed the β‐carboxylation of para‐hydroxystyrene derivatives with excellent regio‐ and (E/Z)‐stereoselectivity by exclusively acting at the β‐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. WILEY-VCH

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

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.

Asymmetric Biocatalytic Cannizzaro‐Type Reaction

Typically, disproportionation reactions furnish 1:1 mixtures of products and are often plagued by unfavorable equilibria; thus, they are commonly considered to be inefficient and are rarely used in organic synthesis. Prominent disproportionation reactions are the Kornblum–DeLaMare rearrangement, the Meerwein–Ponndorf–Verley/Oppenauer reduction/oxidation, the Boudouard reaction, and the catalytic disproportionation of toluene. Among the various disproportionation procedures, the Cannizzaro reaction (CR), which is catalyzed by a strong base (e.g. , KOH), is of special interest, because it allows the transformation of an easily accessible—but somewhat unstable—starting material (an aldehyde) into equimolar amounts of an alcohol and a carboxylic acid, both of which are considerably more stable. In view of its preparative applicability, it is notable that the overall DG value of the CR is negative, which provides a strong driving force in favor of the product formation (see the Supporting Information), as shown in Equation (1).

Regioselective para-Carboxylation of Catechols with a Prenylated Flavin Dependent Decarboxylase

Abstract The utilization of CO2 as a carbon source for organic synthesis meets the urgent demand for more sustainability in the production of chemicals. Herein, we report on the enzyme‐catalyzed para‐carboxylation of catechols, employing 3,4‐dihydroxybenzoic acid decarboxylases (AroY) that belong to the UbiD enzyme family. Crystal structures and accompanying solution data confirmed that AroY utilizes the recently discovered prenylated FMN (prFMN) cofactor, and requires oxidative maturation to form the catalytically competent prFMNiminium species. This study reports on the in vitro reconstitution and activation of a prFMN‐dependent enzyme that is capable of directly carboxylating aromatic catechol substrates under ambient conditions. A reaction mechanism for the reversible decarboxylation involving an intermediate with a single covalent bond between a quinoid adduct and cofactor is proposed, which is distinct from the mechanism of prFMN‐associated 1,3‐dipolar cycloadditions in related enzymes.

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 Enterobacter sp. (FDC_Es) 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% ee. 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 (S)‐selective addition of cyanide is proposed.