Stereochemical aspects of the metabolism of 5-(4'-fluorophenyl)-5-phenylhydantoin in the rat.
Racemic 5-(4'-fluorophenyl)-5-phenylhydantoin was synthesized to examine its metabolism in rat. This compound differs from the antiepileptic agent 5,5-diphenylhydantoin in that the normal site of hydroxylation in 5,5-diphenylhydantoin is blocked on one of the phenyl groups by a fluorine atom. The 4'-fluoro analogue gives a major metabolite, which was isolated and identified as (R)-(-)-5-(4'-fluorophenyl)-5-(4'-hydroxyphenyl)hydantoin of 37% enantiomeric purity. The absolute configuration and enantiomeric purity of the metabolite was determined by chemical conversion to (S)-(-)-5-(4'-hydroxyphenyl)-5-phenylhydantoin. A second metabolite of the catechol type, possibly as a mixture of 5-(3',4'-dihydroxyphenyl)-5-(4'-fluorophenyl)hydantoin, and the corresponding O-3'-methyl derivative was detected by gas chromatography-mass spectrometry after methylation.
D000818:Animals; D001711:Biotransformation; D002849:Chromatography, Gas; D013058:Mass Spectrometry; D010672:Phenytoin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000378:metabolism; D051381:Rats; D013237:Stereoisomerism
C021193:5-(4'-fluorophenyl)-5-phenylhydantoin; D010672:Phenytoin