Syntheses of fjord region bis-dihydrodiol and bis-anti-diol epoxide metabolites of benzo[s]picene

Efficient syntheses of the trans-3,4-trans-9,10-tetrahydroxy-3,4,9,10-tetrahydro derivatives of benzo[s]picene and the corresponding bis-anti-diol epoxide derivatives in which the epoxide rings lie in the sterically crowded fjord regions are reported. Bis-dihydrodiols and bis-anti-diol epoxides of this type are suspected as proximate and ultimate carcinogenic metabolites, respectively, of several polycyclic aromatic hydrocarbons. These are the first examples of this class of molecules to be synthesized, The syntheses entail in the key step double oxidative photocyclization of a tetramethoxy-2,3-distyrylnaphthalene obtained from double Wittig reaction of naphthalene-2,3-dialdehyde. The bis-dihydrodiols were obtained as a mixture of meso and racemic diastereomers separable by HPLC on a reversed-phase ZORBAX ODS column. The bis-anti-diol epoxide enantiomers derived from the latter were resolved by HPLC on a chiral column.