Enzyme Mediated Baeyer-Villiger Oxidations

Abstract

Oxygenation reactions of ketones to esters are referred to as Baeyer-Villiger oxidations and represent a powerful methodology in synthesis to break carbon-carbon bonds in an oxygen insertion process. Since the seminal work by Adolf Baeyer and Victor Villiger in 1899 substantial progress has been made to understand the mechanism, to predict migratory preference, and to apply this conversion in preparative chemistry. Stereoselective Baeyer-Villiger oxidation of cyclic ketones allows rapid access to chiral lactones as valuable intermediates in enantioselective synthesis. Together with organometal catalysts, biocatalysis offers a "green chemistry" methodology for this transformation. Several organisms have been identified to catalyze this reaction in the course of their metabolic pathways and an increasing number of flavin dependent monooxygenases is reported to accept a multitude of non-natural substrates. Such biocatalysts are used in synthetic chemistry either as isolated enzymes in combination with appropriate cofactor recycling systems or as living whole-cells in native or recombinant form. This review gives an overview of the most abundantly utilized enzymes and the corresponding substrate profiles together with applications in natural product and bioactive compound synthesis. The article focuses on recent developments in biocatalytic Baeyer-Villiger oxidation with promising applications in synthetic chemistry. Complementing these aspects, recent advances in characterizing the biochemistry of Baeyer-Villiger monooxygenases and novel approaches to modify and predict the catalytic performance of these enzymes, which have an impact on the potential as stereoselective catalytic entities, are discussed. Keywords: Oxygenases, cyclopentanone monooxygenase, Biotransformations, Desymmetrization reactions, prochiral substrates, kinetic resolution