Arylamination and arylation of 4,4,4-trifluoro-1-phenyl-1,3-butanedione with N-acetoxy derivatives of 2-aminofluorene.
The present study investigated the reaction of carcinogenic electrophiles with beta-diketones which possess an active methylene group. N-Acetoxy-2-(acetylamino)fluorene bound to tRNA at 37 degrees C, pH 7.0, and this reaction was inhibited by 4,4,4-trifluoro-1-phenyl-1,3-butanedione or 2-thenoyltrifluoroacetone. N-Acetoxy-2-(acetylamino)fluorene reacted with these active methylene compounds to form transitory 3-substituted 2-(acetylamino)fluorene intermediates, which, following cleavage of the trifluoroacetyl group, yielded 3-phenacyl-2-(acetylamino)fluorene or 3-(2-thenoylmethyl)-2-(acetylamino)fluorene. N-Acetoxy-2-[(trifluoroacetyl)amino]fluorene reacted with 4,4,4-trifluoro-1-phenyl-1,3-butanedione to yield two products, N-phenacyl-1-(trifluoroacetyl)-2-aminofluorene and N-phenacyl-3-(trifluoroacetyl)-2-aminofluorene. The ratio of these two products was approximately 1:2. The same N-phenacyl products were produced by incubation of the beta-diketone, N-hydroxy-2-(acetylamino)fluorene, and rat liver cytosol which catalyzed the formation of N-acetoxy-2-aminofluorene. Thus, the inhibitions by beta-diketones of nucleic acid-binding and bacterial mutagenesis of carcinogens are likely due to their trapping of the carcinogens.
Wang
C Y
CY
Department of Chemical Carcinogenesis, Michigan Cancer Foundation, Detroit 48201.
Nagase
H
H
Lee
M S
MS
Ksebati
M B
MB
D000099:Acetoxyacetylaminofluorene / Q000737:chemistry*; D002074:Butanones / Q000737:chemistry*; D002273:Carcinogens; D002851:Chromatography, High Pressure Liquid; D013804:Thenoyltrifluoroacetone / Q000737:chemistry
D002074:Butanones; D002273:Carcinogens; C075953:4,4,4-trifluoro-1-phenyl-1,3-butanedione; D013804:Thenoyltrifluoroacetone; D000099:Acetoxyacetylaminofluorene