Stereo-and Regiocontrolled Synthesis of Bay Region syn-and anti-Diol Epoxide Metabolites of Carcinogenic Polycyclic Aromatic Hydrocarbons

抄録

A generally applicable method for the synthesis of the putative, ultimate active metabolites, the bay region syn-and anti-diol epoxides of carcinogenic polycyclic aromatic hydrocarbons has been established. The salient features of this novel and highly efficient method include a cycloaddition between an aryne and 3, 4-dibenzyloxyfuran and the stereo-and regioselective formation of bromo or chloro alcohols, where the halogen atom is placed in the bay region, from the ether-bridge opening of 1β, 4β-epoxy-2α, 3α-carbonyldioxy-1, 2, 3, 4-tetrahydrobenzo ring systems with boron tribromide or trichloride. Mechanistic considerations for the, latter step have been rationalized in terms of the relative stabilities of the tetrahydrobenzo bay and non-bay region benzylic carbocations which have been estimated by the calculations of the heats of formation through the use of the AM1 method. Moreover, these halo alcohol intermediates have been readily resolved into enatiomerically pure form through silica gel flash column chromatography of their chiral derivatives such as (S) -O-methylmandelate esters.