Sangaiah R, Gold A, Newcomb K O, Ball L M
University of North Carolina-Chapel Hill 27599-7400.
J Med Chem. 1991 Feb;34(2):546-9. doi: 10.1021/jm00106a010.
The possibility of bay-region activation of the cyclopenta PAH (polycyclic aromatic hydrocarbon with a peripherally fused cyclopenta ring) benz[j]aceanthrylene (1) was investigated by synthesis and bioassay of the bay-region metabolites trans-9,10-dihydroxy-9,10-dihydrobenz[j]aceanthrylene (4), trans-9,10-dihydroxy-anti-7,8-epoxy-7,8,9,10-tetrahydrobenz[j]a ceanthrylene (2), and 9,10-dihydrobenz[j]aceanthrylene 9,10-oxide (3). The known 1,2-dihydrobenz[j]aceanthrylene-9,10-dione (5) was obtained by published methods; however, the direct route to target dihydrodiol 4, dehydrogenation of the saturated five-membered ring of 5 followed by NaBH4 reduction, gave a poor yield of 4 contaminated with tetrahydrogenated products. Acceptable yields of 4 were obtained by reduction of 5 to the corresponding tetrahydro diol, diacetylation of the diol, and dehydrogenation of the five-membered ring followed by base-catalyzed deacetylation to 4. anti-Diol epoxide 2 was generated by m-chloroperoxybenzoic acid oxidation of 4. Oxide 3 was synthesized by treatment of the monotosylate of 4 with NaOH in monoglyme. Diol epoxide 2 was an active mutagen in Salmonella typhimurium strain TA98 in the absence of metabolic activation, 3 showed marginal activity, while 3 and 4 were mutagenic with metabolic activation. These results coupled with previous studies support activation of benz[j]aceanthrylene via both 2 and cyclopenta ring epoxidation.
通过合成并对湾区代谢产物反式-9,10-二羟基-9,10-二氢苯并[j]并四苯（4）、反式-9,10-二羟基-反式-7,8-环氧-7,8,9,10-四氢苯并[j]并四苯（2）和9,10-二氢苯并[j]并四苯9,10-氧化物（3）进行生物测定，研究了环戊并多环芳烃（具有外围稠合环戊环的多环芳烃）苯并[j]并四苯（1）的湾区活化可能性。已知的1,2-二氢苯并[j]并四苯-9,10-二酮（5）通过已发表的方法获得；然而，制备目标二氢二醇4的直接路线，即5的饱和五元环脱氢后用硼氢化钠还原，产率很低且被四氢化产物污染。通过将5还原为相应的四氢二醇、二醇二乙酰化、五元环脱氢，然后碱催化脱乙酰化得到4，从而获得了可接受产率的4。反式二醇环氧化物2通过间氯过氧苯甲酸氧化4生成。氧化物3通过在单甘醇中用氢氧化钠处理4的单对甲苯磺酸酯合成。二醇环氧化物2在没有代谢活化的情况下对鼠伤寒沙门氏菌TA98菌株是一种活性诱变剂，3表现出微弱活性，而3和4在有代谢活化时具有诱变性。这些结果与先前的研究相结合，支持苯并[j]并四苯通过2和环戊环环氧化的活化作用。
