Stereospecific metabolic reduction of ketones

The stereospecificity of the metabolic reduction of arylalkylketones was investigated. The ketones, propiophenone (I), phenyl-acetone (III), and 1-phenyl-1,2-propanedione (V) were reduced in vitro and in vivo in rats and rabbits to the corresponding alcohols, 1-phenyl-1-propanol (II), 1-phenyl-2-propanol (IV), and 1-phenyl-1,2-propanediol (VIII), respectively. For the analysis, a capillary GLC method employing chiral derivatizing reagents for the resolution of these optically active alcohols was utilized. This study revealed that the metabolic reduction of each ketone produced the corresponding alcohol as a mixture of its enantiomers. With one exception, the mixtures obtained from all in vivo and in vitro reactions were shown to contain at least 70% of one isomer [S(-)-II, S(+)-IV, and erythro-VIII, respectively], with in vitro reduction showing the highest degree of stereospecificity (90-98%). The in vivo reduction of I by the rat was exceptional in that both optical isomers of II were recovered in equal proportions.