216664-12-9Relevant academic research and scientific papers
Synthesis of potentially carcinogenic higher oxidized metabolites of dibenz[a,j]anthracene and benzo[c]chrysene
Harvey, Ronald G.,Dai, Wei,Zhang, Jin-Tao,Cortez, Cecilia
, p. 8118 - 8124 (2007/10/03)
Bis(dihydrodiols) and other higher oxidized metabolites are implicated as active carcinogenic metabolites of polycyclic aromatic hydrocarbons, such as dibenz[a,j]anthracene, that possess more than one bay region in the molecule. The bis(dihydrodiol) metabolites may potentially undergo further metabolism to mono- or diepoxides that combine covalently with DNA or undergo conversion to bis(catechols) that enter into a redox cycle with O2 to form reactive oxygen species that attack DNA. This paper reports convenient syntheses of the terminal ring bis(dihydrodiol) derivatives of dibenz[a,j]anthracene (5) and benzo[c]chrysene (6) via routes that involve in the key steps double oxidative photocyclization of tetramethoxy-substituted diolefins. The latter are synthesized via double Wittig reaction of a bis(phosphonium) salt with 2,3-dimethoxybenzaldehyde. Demethylation of the bis(catechol) products followed by acetylation and reduction with NaBH4 in the presence of O2 affords the bis(dihydrodiol) products. Several additional higher oxidized derivatives of dibenz[a,j]anthracene, specifically the 3,11- diphenol (14a), the 11-hydroxy-3,4-quinone (15), and the 11-hydroxy-trans- 3,4-dihydrodiol (2c), are obtained by an alternative synthesis entailing the reaction of the lithium salt of 1,4-dimethoxy-1,4-cyclohexadiene with 1,3- bis(iodoethyl)benzene to furnish a bis-alkylated diketone which undergoes acid-catalyzed cyclization to 3,11-diketododecahydrodibenz[a,j]anthracene.
