Arylamine-nucleoside adduct formation: evidence for arylnitrene involvement in the reactions of an N-acetoxyarylamine.
N-Acetoxyarylamines are reactive metabolites that are produced from N-arylhydroxamic acids by N-arylhydroxamic acid N,O-acyltransferase and by the acetyl coenzyme A-dependent O-acetylation of N-arylhydroxylamines. Solvolytic decomposition of 7-acetyl-2-(N-acetoxyamino)fluorene (3) afforded 7-acetyl-2-aminofluorene (4) and 7,7'-diacetyl-2,2'-azofluorene (5). Solvolysis of 3 in the presence of 2'-deoxyguanosine resulted in formation of N-(deoxyguanosin-8-yl)-7-acetyl-2-aminofluorene (2), along with smaller yields of 4 and 5 than were obtained in the absence of 2'-deoxyguanosine. The inclusion of nitrene trapping agents, such as piperylene, triethyl phosphite, 1-chloro-4-nitrosobenzene, and oxygen, in the reaction medium with 3 and 2'-deoxyguanosine caused a reduction in the yields of 2, 4, and 5. Additionally, products that would be expected to be formed through reaction with an arylnitrene intermediate were obtained when triethyl phosphite, 1-chloro-4-nitrosobenzene, and oxygen were included in the incubations with 3 and 2'-deoxyguanosine. The results support the proposal that a nitrene intermediate is involved in the formation of 2, 4, and 5 from 3.
Department of Medicinal Chemistry, University of Minnesota, Minneapolis 55455.
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D000588:Amines / Q000737:chemistry*; D001391:Azo Compounds / Q000737:chemistry*; D018736:DNA Adducts / Q000737:chemistry*; D003849:Deoxyguanosine / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry*; D009705:Nucleosides / Q000737:chemistry*
C091862:7-acetyl-N-acetoxy-2-aminofluorene; D000588:Amines; D001391:Azo Compounds; D018736:DNA Adducts; D005449:Fluorenes; D009705:Nucleosides; D003849:Deoxyguanosine