Synthesis and biological activity of bay-region metabolites of a cyclopenta-fused polycyclic aromatic hydrocarbon: benz[j]aceanthrylene.
Synthesis and biological activity of bay-region metabolites of a cyclopenta-fused polycyclic aromatic hydrocarbon: benz[j]aceanthrylene.
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环五稠合多环芳烃湾区代谢物的合成和生物活性：苯并[j]苊。
DOI：
10.1021/jm00106a010
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发表时间：
1991
影响因子：
7.3
通讯作者：
Ball,LM
中科院分区：
文献类型：
--
作者：
Sangaiah,R;Gold,A;Newcomb,KO;Ball,LM
海湾地区的可能性的激活cyclopenta多环芳烃(多环芳烃与周边地融合cyclopenta环)奔驰[/Ąaceanthrylene(1)的合成和生物测定了海湾地区代谢物frarcs-9, 10-dihydroxy-9, 10-dihydrobenz aceanthrylene (/) (4), trans-9, 10-dihydroxy-antz-7, 8-epoxy-7, 8, 9, 10-tetra-hydrobenz aceanthrylene (/) (2), and9, 10-dihydrobenz (/) aceanthrylene 9日10-oxide(3)。已知的1,2 -二氢苯[/]乙炔- 9,10 -二酮(5)通过已发表的方法得到；然而，直接得到目标二氢二醇4的途径是将5的饱和五元环脱氢，然后进行NaBH4还原，这使得4的产率很低，并被四氢化产物污染。通过将5还原为相应的四氢二醇，二醇的二乙酰化，五元环脱氢，然后碱催化脱乙酰化为4，得到了可接受的4的产率。用间氯过氧苯甲酸氧化4生成环氧二醇2。用氢氧化钠在单胺中处理4的单磺酸盐，合成了氧化物3。环氧二醇2在没有代谢激活的情况下对鼠伤寒沙门菌TA98具有活性诱变剂，3具有边际活性，而3和4具有代谢激活的诱变剂。这些结果与先前的研究相结合，支持通过2环和环五环环氧化活化苯并[/']乙炔。
The possibility of bay-region activation of the cyclopenta PAH (polycyclic aromatic hydrocarbon with a peripherally fused cyclopenta ring) benz [/Ąaceanthrylene (1) was investigated by synthesis and bioassay of the bay-region metabolites frarcs-9, 10-dihydroxy-9, 10-dihydrobenz [/] aceanthrylene (4), trans-9, 10-dihydroxy-antz-7, 8-epoxy-7, 8, 9, 10-tetra-hydrobenz [/] aceanthrylene (2), and9, 10-dihydrobenz [/] aceanthrylene 9, 10-oxide (3). The known 1, 2-dihydrobenz [/] 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, diacetylationof the diol, and dehydrogenation of the five-membered ring followed by base-catalyzed deacetylation to 4. arzfz'-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 [/'] aceanthrylene via both 2 and cyclopenta ring epoxidation.