A tailor-made chimeric thiamine diphosphate dependent enzyme for the direct asymmetric synthesis of (S)-benzoins

Article abstract of DOI:10.1002/anie.201405069

Thiamine diphosphate dependent enzymes are well known for catalyzing the asymmetric synthesis of chiral α-hydroxy ketones from simple prochiral substrates. The steric and chemical properties of the enzyme active site define the product spectrum. Enzymes catalyzing the carboligation of aromatic aldehydes to (S)-benzoins have not so far been identified. We were able to close this gap by constructing a chimeric enzyme, which catalyzes the synthesis of various (S)-benzoins with excellent enantiomeric excess (>99) and very good conversion. Hybrid vigor: Combining the active-site characteristics of two thiamine diphosphate (ThDP) dependent enzymes solved the long-standing problem of enzymatic asymmetric (S)-benzoin synthesis starting from commercially available benzaldehydes. The resulting rationally designed hybrid enzyme provides access to various (S)-benzoins with excellent enantiomeric excess and good conversion.