Thiamine-Diphosphate-Dependent Enzymes as Catalytic Tools for the Asymmetric Benzoin-Type Reaction

Benzoin-type reactions allow the generation of α- hydroxy ketones through the (formal) carboligation of two alde- hyde reactants. The synthetic relevance of the products and the wide distribution of the α-hydroxy ketone functionality in bioactive natural compounds have provided the motivation for intensive research efforts directed towards the development of ever more efficient and selective catalysts for reactions of this class. As in many other areas of study, the solution developed in nature – that is, the utilization of thiamine-diphosphate-dependent (ThDP-dependent) enzymes – also in this case allows levels of chemo- and stereoselectivity currently unattainable by biomimetic organocatalysts to be achieved. Here we present an overview of the structural diversity of the α-hydroxy ketone motif achievable through ThDP-dependent enzyme catalysis. Details relating to structure–activity relationships and to ra- tional mutagenesis approaches for improving the catalytic per- formances of wild-type enzymes are also illustrated.