SYNTHESIS AND MUTAGENICITY OF TRANS-DIHYDRODIOL METABOLITES OF BENZO[B]NAPHTHO[2,1-D]THIOPHENE

The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)—trans-1,2-dihydroxy-1,2-dihydrobenzo[6]naphtho[2,1-d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[6]naphtho[2,1-d]thiophene ([2,1]BNT-3,4-diol)—are described. The syntheses involved preparation of the appropriate 1-(3-benzo[b]-thiopheneyl)-2-(methoxyphenyl)ethylenes followed by photocyclization to methoxy-[2,1]BNTs, hydrolysis to hydroxy-[2,1]BNTs, oxidation to [2,1]BNT-diones, and NaBH4 reduction. The dihydrodiols were tested for mutagenicity in Salmonella typhimurium TA 100 with activation; [2,1]BNT-3,4-diol, which can form a bay region diol epoxide, was as mutagenic as [2,1]BNT whereas [2,1]BNT-1,2-diol was inactive. These results suggest that the metabolic activation of [2,1]BNT proceeds partially via formation of a bay region diol epoxide. © 1990, American Chemical Society. All rights reserved.