Synthesis and mutagenicity of A-ring reduced analogs of 7,12-dimethylbenz[a]anthracene
作者:Muthiah N. Inbasekaran、Donald T. Witiak、Karen Barone、John C. Loper
DOI:10.1021/jm00177a013
日期:1980.3
The synthesis and mutagenicity of two derivatives of 7,12-dimethylbenz[a]anthracene (DMBA; 1), i.e., 1,2-H2DMBA (4) and 1,2,3,4-H4DMBA (5), are reported. These analogues (4 and 5) represent dihydro and tetrahydro A-ring reduced forms of DMBA, a region in the parent hydrocarbon (1) proposed to be involved in metabolism to the ultimate carcinogen. The synthesis for 4 without isolation of intermediates
报道了7,12-二甲基苯并[a]蒽(DMBA; 1)的两种衍生物,即1,2-H2DMBA(4)和1,2,3,4-H4DMBA(5)的合成和致突变性。这些类似物(4和5)代表DMBA的二氢和四氢A环还原形式,DMBA是母体烃(1)中提议参与最终致癌物代谢的区域。通过与8摩尔当量的CH3Li,HI和NaBH4连续反应,合成4,而无需从1,2,3,4-四氢苯并[a]蒽-4,7,12-三酮(10)的甲苯磺酰isolation中分离中间体代表了这种烃的新颖方法,目前已有足够数量的生物研究用。有趣的是,在存在或不存在针对菌株TA98和TA100的微粒体激活的情况下,这些还原的类似物4和5在Ames测定中均表现出诱变活性。在这些菌株中 DMBA仅在存在S-9馏分时才有活性。在缺乏质粒的菌株TA1537中,在不存在和存在S-9级分的情况下,仅四氢类似物5显示出诱变活性。