A novel 3,4-dibenzyloxyfuran cycloaddition approach towards the synthesis of diol epoxides of the carcinogenic polycyclic aromatic hydrocarbons and (+,-)-methyl triacetylshikimate.

A novel, highly efficient method generally applicable to the synthesis of both syn- and anti-diol epoxide metabolites of polycyclic aromatic hydrocarbons (PAHs) has been developed. The two key steps employed in this approach are an initial cycloaddition reaction between an aryne generated in situ and 3,4-dibenzyloxyfuran, and a crucial ether bridge opening of the 1,2,3,4-tetrahydropolyarene 1,4-endoxides at a benzylic carbon upon treatment with BBr$\sb3$. The direction of the 1,4-ether bridge opening of the non-symmetric ether intermediate (phenanthrene series) has been shown to be dependent upon the nature of the 2,3-diol protecting group. The diacetate intermediate underwent ring opening at the non-bay-region benzylic carbon giving rise to the bromoalcohol with the bromine incorporated at this position. Conversely the corresponding 2,3-carbonate resulted in ring opening and the bay-region benzylic carbon. Both reactions proceeded in excellent yield with retention of configuration. Synthetic bay-region syn- and anti-diol epoxides of the carcinogen 1,4-dimethylphenanthrene have been found to exhibit exceptional potency as mutagens in both Salmonella typhimurium bacterial cells (in vitro) and bone marrow cells of mice (in vivo). Furthermore, biologically significant dimethylphenanthrene regioisomers such as 1,4-dimethylphenanthrene, 2,4-dimethylphenanthrene, and 3,4-dimethylphenanthrene were synthesized using a mild and efficient direct deoxygenation of the corresponding 1,4-endoxides. The use of excess trimethylsilyl iodide (3.0 equiv.) was found to be effective for the conversion of 1,4-endoxides to the corresponding arenes. Additionally, in order to explore the potential of 3,4-dibenzyloxyfuran as a versatile reagent, a highly efficient five-step synthesis of ($\pm$)-methyl triacetylshikimate was accomplished in 60.1% overall yield from the furan.Ph.D.Organic chemistryPure SciencesUniversity of Michigan, Horace H. Rackham School of Graduate Studieshttp://deepblue.lib.umich.edu/bitstream/2027.42/128265/2/8907063.pd