ASYMMETRIC SYNTHESIS OF PHENYL-RING-CONTAINING ALCOHOLS USING THERMOANAEROBACTER ETHANOLICUS W110A SECONDARY ALCOHOL DEHYDROGENASE by MUSA

An enantioselective asymmetric reduction of phenyl ring-containing prochiral ketones toyield the corresponding optically active secondary alcohols was achieved with W110Asecondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (W110A TeSADH) inTris-HCl buffer using 2-propanol (30%, v/v) as cosolvent and cosubstrate. This concentration of2-propanol was crucial not only to enhance the solubility of hydrophobic phenyl ring-containingsubstrates in the aqueous reaction medium, but also to shift the equilibrium in the reductiondirection. The resulting alcohols have S-configuration, in agreement with Prelog’s rule, in whichthe nicotinamide-adenine dinucleotide phosphate (NADPH) cofactor transfers its pro-R hydrideto the re face of the ketone. A series of phenyl ring-containing ketones, such as 4-phenyl-2-butanone (1a) and 1-phenyl-1,3-butadione (2a), were reduced with good to excellent yields andhigh enantioselectivities. On the other hand, 1-phenyl-2-propanone (7a) was reduced with loweree than 2-butanone derivatives. (R)-Alcohols, the anti-Prelog products, were obtained byenantiospecific oxidation of (S)-alcohols through oxidative kinetic resolution of the rac-alcoholsusing W110A TeSADH in Tris-HCl buffer/acetone (90:10, v/v).