Synthesis of suspected carcinogenic metabolites of 7H-benzo[c]fluorene, a coal tar component implicated in causation of lung tumors.
High incidences of lung tumors were observed in mice fed coal tar in their diet. The principal component of tar that gives rise to DNA-bound adducts in mouse lung was identified as 7H-benzo[c]fluorene (BcF). We now report the synthesis of suspected active metabolites of BcF, specifically the trans-3,4-dihydrodiol of BcF (2), its likely proximate carcinogenic metabolite, and the corresponding anti- and syn-diol epoxides of BcF (3 and 4) in which the epoxide ring resides in the pseudobay region. The diol epoxide derivatives (3 and 4) are postulated to be ultimate carcinogenic metabolites of BcF that bind to DNA in mouse lung.
Ben May Institute for Cancer Research, University of Chicago, Chicago, Illinois 60637, USA.
Ji-Quan
JQ
Wang
Eric H
EH
Weyand
Ronald G
RG
Harvey
D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D003033:Coal Tar / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D018736:DNA Adducts / Q000032:analysis / Q000096:biosynthesis*; D005449:Fluorenes / Q000138:chemical synthesis* / Q000633:toxicity*; D008175:Lung Neoplasms / Q000139:chemically induced*; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D015394:Molecular Structure; D013237:Stereoisomerism
D002273:Carcinogens; D018736:DNA Adducts; D005449:Fluorenes; C041513:benzo(c)fluorene; D003033:Coal Tar; D004247:DNA