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

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

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.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Carcinogenicity Tests
  • Heterocyclic Compounds / chemical synthesis*
  • Heterocyclic Compounds / toxicity
  • Mutagenicity Tests
  • Polycyclic Compounds / chemical synthesis*
  • Polycyclic Compounds / metabolism*
  • Polycyclic Compounds / toxicity
  • Thiophenes / chemical synthesis*
  • Thiophenes / metabolism*
  • Thiophenes / toxicity

Substances

  • Heterocyclic Compounds
  • Polycyclic Compounds
  • Thiophenes
  • 1,2-dihydroxy-1,2-dihydrobenzo(b)naphtho(2,1-d)thiophene
  • 3,4-dihydroxy-3,4-dihydrobenzo(b)naphtho(2,1-d)thiophene
  • benzo(b)naphtho(2,1-d)thiophene