Enantioselective ring opening of epoxides with cyanide catalysed by halohydrin dehalogenases:: A new approach to non-racemic β-hydroxy nitriles

Halohydrin dehalogenases (HheA, HheB and HheC) were found to efficiently catalyse a carbon-carbon bond forming reaction between terminal aliphatic epoxides and cyanide, yielding beta-hydroxy nitriles. With all three enzymes nucleophilic ring opening of epoxides proceeds with high regioselectivity to the beta-carbon atom. Activity, enantioselectivity and enantiopreference depend on the type of enzyme and the substrate structure. HheC was found to be the most selective among the tested enzymes. The enantioselectivity toward monosubstituted epoxides varies from moderate to high (E = 5-106), while resolution of 2,2-disubstituted epoxides proceeds with very high enantioselectivity (E = 141 and 200). The results show that halohydrin dehalogenases may become attractive catalysts for the facile preparation of enantiopure beta-hydroxy nitriles from racemic epoxides.