The enantioselective metabolism of p-cymene in rabbits.
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 omega-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 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 derivatives were also synthesized as standard compounds.
Matsumoto
T
T
Department of Applied Material Science, Faculty of Integrated Arts and Sciences, University of Tokushima, Japan.
Ishida
T
T
Yoshida
T
T
Terao
H
H
Takeda
Y
Y
Asakawa
Y
Y
D000818:Animals; D001711:Biotransformation; D000081007:Cymenes; D005260:Female; D008297:Male; D039821:Monoterpenes; D011817:Rabbits; D013237:Stereoisomerism; D013729:Terpenes / Q000302:isolation & purification* / Q000493:pharmacokinetics
D000081007:Cymenes; D039821:Monoterpenes; D013729:Terpenes; C007210:4-cymene