Structure Elucidation of the Adducts Formed by Fjord-Region Dibenzo[a,l]pyrene 11,12-Dihydrodiol 13,14-Epoxides and Deoxyadenosine

Model adducts to be used in the identification of biologically formed adducts were synthesized by reaction of fjord-region dibenzo[a,l]pyrene 11,12-dihydrodiol 13,14-epoxides (DB[a,llPDE) and deoxyadenosine (dA). The (±)-anti-DB[a,l]PDE was reacted with dA in dimethylformamide at 100 °C for 30 min to give four DB[a,l]PDE-14-N^6dA adducts: (-)-anti-trans (26%), (+)anti-trans (26%), (-)-anti-cis (17%), and (+)-anti-cis (17%). The (±)-syn-DB[a,l]PDE was reacted with dA under the same conditions to yield four DB[a,l]PDE-14-N6A adducts and one N7Ade adduct: (+)-syn-cis (19%), (+)-syn-trans (13%), (-)-syn-cis (19%), (-)-syn-trans (13%), and (±)syn-DB[a,l]PDE-14-N7Ade (22%). The structures of the eight stereoisomers ofDB[a,l]PDE14-N6dA were unequivocally assigned by reacting optically pure (-)-anti-DB[a,l]PDE and (+)s3ʹ7i-DB[a,/]PDE with dA and by a combination of NMR, circular dichroism, and fast atom bombardment mass spectrometry. Reactions at 100 °C yielded mainly the trans-opened adducts at the benzylic C-14 position for both (±)-anti-DB[a,l]PDE and (-)-anti-DB[a,l]PDE, whereas (±)-syn-DB[a,l]PDE and (+)-syn-DB[a,l]PDE afforded mainly cis-opened adducts. At room temperature, however, only trans-opened adducts were obtained from (+-)-anti-DB[a,l]PDE and only cis-opened adducts from (±)-syn-DB[a,l]PDE. Steric hindrance created by the fjord region may be an important factor for the stereoselectivity observed at room temperature.