Premercapturic acid metabolites of bromobenzene derived via its 2,3- and 3,4-oxide metabolites.
1. A new premercapturic acid metabolite of bromobenzene was isolated from the urine of beta-naphthoflavone-induced rats; using 1H-n.m.r., FAB mass spectrometry and chemical degradation it was identified as S-(2-hydroxy-3-bromocyclohexa-3,5-dienyl)-N-acetylcysteine. 2. Two regioisomeric premercapturic acids apparently derived from bromobenzene-3,4-oxide were isolated as an inseparable 1:1 mixture from the urine of phenobarbital-induced rats and characterized by similar means. 3. Acid dehydration of bromobenzene 3,4- and 4,3-premercapturic acids (mixture) afforded only p-bromophenylmercapturic acid, whereas acid dehydration of 3,2-premercapturic acid gave both o- and m-bromophenylmercapturic acids. This implies a shift of sulphur in acid dehydration of the 3,4- and 3,2- but not the 4,3-premercapturic acids. 4. Base dehydration of the 3,4- and 4,3-premercapturic acid mixture gave a mixture of p- and m-bromophenylmercapturic acids, whereas base dehydration of the 3,2-premercapturic acid gave only m-bromophenylmercapturic acid. This indicates these premercapturic acids dehydrate by direct elimination without rearrangment. 5. The 3,2-premercapturic acid was detected only in the urine of BNF-induced animals, whereas the 3,4- and 4,3-premercapturic acids were detected in the urines of untreated as well as PB- and BNF-induced animals. 6. Together with earlier reports of the isolation of the 2,3-dihydrodiol, the isolation of the 3,2-premercapturic acid as a urinary metabolite of bromobenzene implies that bromobenzene-2,3-oxide is a discrete metabolite of bromobenzene and not merely a hypothetical intermediate.
Zheng
J
J
Department of Medicinal Chemistry, School of Pharmacy, University of Kansas, Lawrence 66045-2506.
Hanzlik
R P
RP
D000111:Acetylcysteine / Q000031:analogs & derivatives / Q000378:metabolism / Q000652:urine*; D000818:Animals; D001969:Bromobenzenes / Q000378:metabolism*; D002851:Chromatography, High Pressure Liquid; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D051381:Rats; D014867:Water / Q000737:chemistry
D001969:Bromobenzenes; D014867:Water; C070956:3,4-premercapturic acid; C070957:3,2-premercapturic acid; C070955:4,3-premercapturic acid; C032036:bromobenzene; D000111:Acetylcysteine