Enzymatic Methods

Abstract

This chapter deals with the use of biocatalysts for achieving DKR. In view of the particularly mild conditions associated with enzyme-catalysed DKR processes, combined to the fact that these reactions are often remarkably enantio- and regioselective, the use of biocatalysts for achieving DKR has become an increasingly attractive alternative to conventional chemical methods. In recent years, impressive examples using new enzymes and major progress in DKR have taken place, demonstrating that biocatalysis is rapidly developing and is still a growing field, allowing a number of key intermediates for pharmaceutical synthesis to be reached. As an example, a number of various activated ketones, such as β-ketoesters, β-ketoaldehydes, β-ketoamides, β-ketosulfones, β-ketonitriles, and α-ketolactones have been highly efficiently reduced under enzymatic conditions. Moreover, 2-phenylpropanaldehyde and derivatives could be reduced with excellent yields and enantioselectivities by using HLADH to give access to chiral pharmaceutical products of the Profen class. An even greater number of efficient esterification and hydrolysis enzymatic reactions have also been developed, providing an impressive collection of variously functionalised chiral products. In addition, DKRs of amines have been recently successfully developed. For example, the DKR of a series of amines compatible with remote functionalities was achieved through a highly efficient one-pot sequential DKR process, involving an in situ free radical-mediated racemisation and an enzymatic resolution.