Enzymatic Routes to Enantiomerically Pure Aromatic α-Hydroxy Carboxylic Acids: A Further Example for the Diversity of Biocatalysis

Abstract

An important class of compounds which can be produced by means of enzymatic routes are enantiomerically pure aromatic α-hydroxy carboxylic acids, in particular mandelic acid and derivatives thereof. Numerous different types of enantioselective biocatalytic approaches to these target molecules have been developed. Among them are chiral enzymatic resolution processes using racemic precursors as well as asymmetric catalytic methods starting from prochiral compounds. Regarding the resolution processes, nitrilase-catalyzed hydrolysis and dehydrocyanation of racemic cyanohydrins as well as stereocontrolled ester cleavage of O-acetylcyanohydrins and α-hydroxy carboxylic acid esters, respectively, have been developed. Main contributions in the field of asymmetric catalytic concepts are the asymmetric reduction of α-keto acids as well as the asymmetric hydrocyanation of aldehydes. In the latter case, a subsequent chemical hydrolysis gives the desired products. In the following, these different concepts for the biocatalytic preparation of aromatic α-hydroxy carboxylic acid are discussed showing that biocatalysis can provide the organic chemist with many versatile synthetic pathways to obtain chiral aromatic α-hydroxy carboxylic acids. 1 Introduction 2 Overview: Biocatalytic Routes to Aromatic α-Hydroxy Carboxylic Acids 3 Route A: Enzymatic Hydrolysis of an Ester Group 4 Route B: Biocatalytic Transesterification − Enzymatic Hydrolysis of the O-Acetyl Group 5 Route C: Enzymatic Hydrolysis of the Cyano Group 6 Route D: Enzymatic Cleavage of rac-Cyanohydrins 7 Route E: Enantioselective Biocatalytic Hydrocyanation of Aromatic Aldehydes 7.1 Enzymatic Enantioselective Hydrocyanation in Organic Media 7.2 Enzymatic Enantioselective Hydrocyanation in Aqueous Media 7.3 Enzymatic Enantioselective Hydrocyanation in Biphasic Solvent Systems 7.4 Chemical Hydrolysis of Enantiomerically Enriched Cyanohydrins 8 Route F: Enantioselective Reduction of α-Keto Acids and Esters Thereof 9 Summary and Outlook