苯并[b]萘并[2,1-d]噻吩反式二氢二醇代谢物的合成与致突变性

Synthesis and mutagenicity of trans-dihydrodiol metabolites of benzo[b]naphtho[2,1-d]thiophene.

作者信息

Misra B, Amin S

机构信息

Division of Chemical Carcinogenesis, Naylor Dana Institute for Disease Prevention, American Health Foundation, Valhalla, New York 10595.

出版信息

Chem Res Toxicol. 1990 Mar-Apr;3(2):93-7. doi: 10.1021/tx00014a002.

DOI:10.1021/tx00014a002

PMID:1718470

Abstract

The syntheses of potentially important metabolites of benzo[b]naphtho[2,1-d]thiophene ([2,1]BNT)--trans-1,2-dihydroxy-1,2-dihydrobenzo[b]naphtho[2,1- d]thiophene ([2,1]BNT-1,2-diol) and trans-3,4-dihydroxy-3,4-dihydrobenzo[b]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.

摘要

描述了苯并[b]萘并[2,1-d]噻吩（[2,1]BNT）潜在重要代谢物——反式-1,2-二羟基-1,2-二氢苯并[b]萘并[2,1-d]噻吩（[2,1]BNT-1,2-二醇）和反式-3,4-二羟基-3,4-二氢苯并[b]萘并[2,1-d]噻吩（[2,1]BNT-3,4-二醇）的合成。合成过程包括制备合适的1-(3-苯并[b]噻吩基)-2-(甲氧基苯基)乙烯，然后光环化生成甲氧基-[2,1]BNT，水解生成羟基-[2,1]BNT，氧化生成[2,1]BNT-二酮，以及用NaBH4还原。对二氢二醇在有活化剂存在的情况下于鼠伤寒沙门氏菌TA 100中进行了致突变性测试；能够形成湾区二醇环氧化物的[2,1]BNT-3,4-二醇与[2,1]BNT具有相同的致突变性，而[2,1]BNT-1,2-二醇无活性。这些结果表明，[2,1]BNT的代谢活化部分通过形成湾区二醇环氧化物进行。