Asymmetric reduction and oxidation of aromatic ketones and alcohols using W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus.
An enantioselective asymmetric reduction of phenyl ring-containing prochiral ketones to yield the corresponding optically active secondary alcohols was achieved with W110A secondary alcohol dehydrogenase from Thermoanaerobacter ethanolicus (W110A TESADH) in Tris buffer using 2-propanol (30%, v/v) as cosolvent and cosubstrate. This concentration of 2-propanol was crucial not only to enhance the solubility of hydrophobic phenyl ring-containing substrates in the aqueous reaction medium, but also to shift the equilibrium in the reduction direction. The resulting alcohols have S-configuration, in agreement with Prelog's rule, in which the nicotinamide-adenine dinucleotide phosphate (NADPH) cofactor transfers its pro-R hydride to 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 and high enantioselectivities. On the other hand, 1-phenyl-2-propanone (7a) was reduced with lower ee than 2-butanone derivatives. (R)-Alcohols, the anti-Prelog products, were obtained by enantiospecific oxidation of (S)-alcohols through oxidative kinetic resolution of the rac-alcohols using W110A TESADH in Tris buffer/acetone (90:10, v/v).
Musa
Musa M
MM
Department of Chemistry, University of Georgia, Athens, Georgia 30602, USA.
Ziegelmann-Fjeld
Karla I
KI
Vieille
Claire
C
Zeikus
J Gregory
JG
Phillips
Robert S
RS
D000426:Alcohol Dehydrogenase / Q000235:genetics / Q000378:metabolism*; D000438:Alcohols / Q000737:chemistry* / Q000378:metabolism*; D002849:Chromatography, Gas; D007659:Ketones / Q000737:chemistry* / Q000378:metabolism*; D015394:Molecular Structure; D010084:Oxidation-Reduction; D013379:Substrate Specificity; D046968:Thermoanaerobacter / Q000201:enzymology; D014364:Tryptophan / Q000235:genetics / Q000378:metabolism*
D000438:Alcohols; D007659:Ketones; D014364:Tryptophan; D000426:Alcohol Dehydrogenase