Thiamin-Diphosphate-Dependent Enzymes: New Aspects of Asymmetric CC Bond Formation

Starting from a thorough investigation of mechanistic aspects of ThDP-dependent (ThDP=thiamin diphosphate) enzymes in combination with mutagenesis studies and a detailed substrate screening, new general synthetic methods have been developed based on Umpolung reactions by thiamin catalysis. A selective donor–acceptor concept was established leading to the first asymmetric cross-benzoin condensation, and a kinetic racemic resolution through CC bond cleavage was developed. With these tools and in combination with protein engineering, we approached the synthesis of new chiral building blocks on a preparative scale. An outlook is given with respect to the potential of other ThDP-dependent enzymes as catalysts in asymmetric synthesis.