Synthesis and carcinogenic activity of 5-fluoro-7-(oxygenated methyl)-12-methylvenz[a]anthracenes.
Treatment of 7,12-benz[a]anthraquinone (2) with methylmagnesium iodide or methyllithium yields mixtures of cis- and trans-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (3a,b), in which the ratio of cis to trans lies in the 3--4:1 region. Each isomer afforded high yields of 7-chloromethyl-12-methylbenz[a]anthracene (5) on treatment with hydrogen chloride in ethyl acetate. Similarly, 5-fluoro-7,12-benz[a]anthraquinone (8) afforded a mixture of cis- and trans-5-fluoro-7,12-dihydro-7,12-dihydroxy-7,12-dimethylbenz[a]anthracenes (9) which yielded 7-chloromethyl-5-fluoro-12-methylbenz[a]anthracene (10) on treatment with HCl. The chloromethyl compounds, 5 and 10, yielded 7-acetoxymethyl-12-methylbenz[a]anthracene (6) and 7-acetoxymethyl-5-fluoro-12-methylbenz[a]anthracene (11) on treatment with acetate ion. Hydrolysis of 6 and 11 yielded 7-hydroxymethyl-12-methylbenz[a]anthracene (7) and 5-fluoro-7-hydroxymethyl-12-methylbenz[a]anthracene (12), respectively. Since neither 11 nor 12 is appreciably carcinogenic, the carcinogenic metabolism of 7,12-dimethylbenz[a]anthracene (DMBA) probably does not involve attack at the 7-methyl group.
D015127:9,10-Dimethyl-1,2-benzanthracene / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D001551:Benz(a)Anthracenes / Q000138:chemical synthesis*; D002273:Carcinogens / Q000138:chemical synthesis*; D007279:Injections, Subcutaneous; D008297:Male; D051381:Rats; D012513:Sarcoma, Experimental / Q000139:chemically induced; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013997:Time Factors
D001551:Benz(a)Anthracenes; D002273:Carcinogens; D015127:9,10-Dimethyl-1,2-benzanthracene