Synthesis of dihydrodiol metabolites implicated in the mechanism of carcinogenesis of phenanthro[4,3-b][1]benzothiophene and phenanthro[3,4-b][1]benzothiophene, the polycyclic sulfur heterocycles with a "Fjord" structure.
Dihydrodiols, which are potential proximate carcinogens of phenanthro[4,3-b][1]benzothiophene (3) and phenanthro[3,4-b][1]benzothiophene (4) and possess a "fjord" structure, were synthesized. The dihydrodiols synthesized were trans-3,4-dihydroxy-3,4-dihydrophenanthro[4,3-b][1]benzothiophene (5) and trans-3,4-dihydroxy-3,4-dihydrophenanthro[3,4-b][1]benzothiophene (6). The precursors to the dihydrodiols 5 and 6 were 3-methoxyphenanthro[4,3-b][1]benzothiophene (11) and 3-methoxyphenanthro[3,4-b][1]benzothiophene (16). Compound 11 was obtained via Suzuki cross-coupling reaction of easily accessible starting materials. However, this synthetic strategy utilizing Suzuki reaction for the preparation of 16 was comparatively less productive than that described previously due to time-consuming synthesis of the starting material(s), and extremely poor yield associated with cyclization of the epoxide 15 to 16. The methoxy derivatives 11 and 16 were converted to the corresponding dihydrodiols 5 and 6 by a sequence involving demethylation, oxidation, and reduction. The trans-stereochemistry of the dihydrodiols was established by (1)H NMR, which indicated a large coupling constant between vicinal carbinol protons. The UV spectra of the dihydrodiols 5 and 6 are presented.
Kumar
Subodh
S
Environmental Toxicology and Chemistry Laboratory, Great Lakes Center, State University of New York College at Buffalo, 1300 Elmwood Avenue, 14222, USA.
D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002384:Catalysis; D003500:Cyclization; D006576:Heterocyclic Compounds, 4 or More Rings / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D009152:Mutagenicity Tests; D009153:Mutagens / Q000138:chemical synthesis* / Q000494:pharmacology; D010084:Oxidation-Reduction; D010616:Phenanthrenes / Q000494:pharmacology*; D012486:Salmonella typhimurium / Q000187:drug effects*; D013056:Spectrophotometry, Ultraviolet; D013237:Stereoisomerism; D013457:Sulfur Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D013876:Thiophenes / Q000494:pharmacology*
D002273:Carcinogens; D006576:Heterocyclic Compounds, 4 or More Rings; D009153:Mutagens; D010616:Phenanthrenes; D013457:Sulfur Compounds; D013876:Thiophenes; C473589:phenanthro(4,3-b)(1)benzothiophene