Highly enantioselective biomimetic intramolecular dehydration: kinetic resolution of β-hydroxy ketones catalyzed by β-turn tetrapeptides

Racemic beta-hydroxy ketones were kinetically resoluted into the enantiopure isomers and (E)-alpha,beta-unsaturated ketones using catalytic asymmetric intramolecular dehydration for the first time. Synthetic tetrapeptides were used to imitate fatty acid dehydratases to efficiently discriminate racemic beta-hydroxy ketones, enantioselectively catalyze the intramolecular dehydration, and result in highly enantioenriched beta-hydroxy and (E)-alpha,beta-unsaturated ketones in the environmentally benign process. Mechanistically, the high discrimination of the racemic substrates and successive enantioselective dehydration are highly dependent on the cooperative catalysis of the NH2 and COOH groups of the peptide. (C) 2013 Elsevier Ltd. All rights reserved.