The enantiomeric purity of alcohols formed by enzymatic reduction of ketones can be improved by optimisation of the temperature and by using a high co-substrate concentration

Abstract

The stereoselective reduction of ketones by alcohol dehydrogenase from Thermoanaerobium brockii was studied in organic reaction media. 2-Propanol was used as co-substrate to regenerate the coenzyme NADPH. The enantiomeric excess of the alcohol formed from the ketone decreased during the course of the reaction (from 53 to 0% e.e. in the formation of ( R)-2-butanol). This was interpreted as being due to the reversibility of all the reactions involved. By using a large excess of 2-propanol this effect was suppressed. In the reduction of 2-butanone to ( R)-2-butanol, the enantiomeric excess increased with increasing temperature, but in the reduction of 2-pentanone to ( S)-2-pentanol the enantiomeric excess decreased with increasing temperature. The data were evaluated in terms of free energy of activation of the reaction pathways leading to the different possible products.