Abstract
p-Cymene (1) was metabolized in rabbits and the following four optically active metabolites, 2-(p-tolyl)-1-propanol (3' : R/S=65 : 35), 2-(p-tolyl)propanoic acid (5' : R/S=0 : 100), p-(2-hydroxy-1-methylethyl)benzoic acid (6' : R/S=91 : 9) and p-(1-carboxyethyl)benzoic acid (8' : R/S=30 : 70), were isolated in addition to three optically inactive metabolites, 2-(p-tolyl)-2-propanol (2), p-isopropylbenzoic acid (4'), and p-(1-hydroxy-1-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 ω-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 and derivatives, but the R-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 derivative were also synthesized as standard compounds.
