Synthesis of Fjord region diol epoxides as potential ultimate carcinogens of dibenzo[a,l]pyrene

Chem Res Toxicol. Mar-Apr 1994;7(2):125-9. doi: 10.1021/tx00038a002.

Abstract

Dibenzo[a,l]pyrene (DB[a,l]P) is one of the strongest polynuclear aromatic hydrocarbon carcinogens known. This paper describes the synthesis of potential ultimate carcinogens of DB[a,l]P: anti- and syn-11,12-dihydroxy-13,14-epoxy-11,12,13,14- tetrahydroDB[a,l]P (DB-[a,l]P-11,12-diol-13,14-epoxides). The method employed is also useful for the preparation of key intermediates for the synthesis of 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrobenzo-[g]chrysene (BgC-11,12-diol-13,14-epoxide). Photochemical cyclization of the appropriately substituted phenanthrylphenylethylenes provided 9-carbomethoxy-11-methoxyBgC (4) and 11-methoxyBgC (3). The former was converted by reduction, oxidation, one-carbon chain extension, and cyclization to 11-methoxy DB[a,l]P (7). Compounds 3 and 7 were converted by hydrolysis and oxidation to BgC-11,12-dione (10) and DB[a,l]P-11,12-dione (11), respectively. The diones are the precursors for the synthesis of the corresponding diol epoxides. anti- and syn-DB-[a,l]P-11,12-diol-13,14-epoxides 13 and 14 were prepared in 38% and 55% yields, respectively, from 11. Both diol epoxides had predominantly pseudodiequatorial hydroxyl groups, as seen in other sterically hindered diol epoxides.

Publication types

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

MeSH terms

  • Benzopyrenes / chemical synthesis*
  • Benzopyrenes / chemistry*
  • Carcinogens / chemistry*
  • Epoxy Compounds / chemical synthesis*
  • Stereoisomerism

Substances

  • Benzopyrenes
  • Carcinogens
  • Epoxy Compounds
  • 11,12-dihydroxy-13,14-epoxy-11,12,13,14-tetrahydrodibenzo(a,l)pyrene
  • dibenzo(a,l)pyrene