The Enantioselective Metabolism of p-Cmene in Rabbits

Abstract

p-Cymene (1) was metabolized in rabbits and the following four optically active metabolites, 2-(p-tolyl)-l-propanol (3': R/S=65:35), 2-(p-tolyl)propanoic acid (5': R/S=0:100), p-(2-hydroxy-l-methylethyl)benzoic acid (6': R/S=91:9) and p-(l-carboxyethyl)benzoic acid (8': R/S=30:10), were isolated in addition to three optically inactive metabolites, 2-(p-tolyl)-2-propanol (2),Msopropylbenzoic acid (4'), and p-(l-hydroxy-l-methylethyl)benzoic acid (7'). The presumed metabolic pathways of p-cymene in rabbits were confirmed by the administration of the intermediate metabolites (2, 3’, 4’, and 5’). The enantiomeric ratios of the metabolites, 3’ and 6’, suggested that eo-hydroxylations of the isopropyl group in 1 and 4’ occurred preferentially at the pro-S methyl group. In the metabolism of 1, the S-isomers are predominant in the propanoic acid derivatives, but the β-isomers are rich in the propanol derivatives. It is of interest that the metabolism of 4’, however, produced predominantly the corresponding propanol derivative (6'; R/S= 91:9) and propanoic acid derivative (8'; R/S= 80:20) possessing the same R-configuration. Some optically active p-cymene derivatives were also synthesized as standard compounds. © 1992, The Pharmaceutical Society of Japan. All rights reserved.