ENZYMATIC RESOLUTION OF 1-PHENYL-1,2-ETHANEDIOL BY ENANTIOSELECTIVE OXIDATION - OVERCOMING PRODUCT INHIBITION BY CONTINUOUS EXTRACTION

Oxidations of alcohols by alcohol dehydrogenases often suffer from low conversions and slow reaction rates due to severe product inhibition. This can be overcome by continuous product extraction, because only t he concentrations, but not the kinetic parameters, can be changed. As a consequence, it is favorable to apply a differential circulation rea ctor with continuous product extraction, where only a small amount of product is formed per cycle. The product is then directly extracted us ing a microporous hydrophobic hollow fiber membrane. This results in a n increase of the relative activity of the dehydrogenase at a given co nversion. The reaction investigated is the kinetic resolution of racem ic 1-phenyl-1,2-ethanediol by glycerol dehydrogenase (GDH). The result ing oxidation product, 2-hydroxyacetophenone, causes a strong product inhibition. Additionally, it reacts in a chemical reaction with the co factor lowering its active concentration. Because the GDH needs beta-n icotinamide adenine dinucleotide (NAD(+)) as a cofactor, lactate dehyd rogenase is used to regenerate NAD(+) from NADH by reducing pyruvate t o (L)-lactate. A conversion of 50% with respect to the racemate and an enantiomeric excess >99% of the (S)-enantiomer was reached. (C) 1996 John Wiley & Sons, Inc.