Diversity of ThDP‐Dependent Enzymes Forming Chiral Tertiary Alcohols

Thiamine diphosphate (ThDP)‐dependent enzymes are well known biocatalysts for CC bond–forming reactions. While this enzyme class is mainly investigated for the formation of acyloins of secondary alcohols, recent studies have expanded its scope to utilize ketones as electrophiles in asymmetric carboligation reactions for the formation of tertiary alcohols. Chiral tertiary alcohols are ubiquitous motifs in natural products and important building blocks for the synthesis of bioactive compounds. ThDP‐dependent enzymes are emerging as one of the most promising classes of biocatalysts for synthesizing a wide range of products due to the variety of possible substrate combinations, accessible starting materials, high enantioselectivity, and advantageous self‐regeneration of the catalytic ThDP cofactor. This review provides an overview of the ThDP‐dependent enzymes (e.g., decarboxylase, DC; transketolase, TK; α‐keto acid dehydrogenase 2, αKADH2) that form tertiary alcohols, focusing on the substrate scope and diversity of physiological functions. The available toolbox and the characterized reactions shall serve as a starting point for future studies. Inspired by nature, an even broader diversity of classes and substrate specificities is expected in this field.