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 adduc ts were synthesized by reaction of fjord-region dibenzo[a,l]pyrene 11,12-di hydrodiol 13,14-epoxides (DB[a,l]PDE) and deoxyadenosine (dA). The (+/-)-an ti-DB[a,l]PDE was reacted with dA in dimethylformamide at 100 degrees C for 30 min to give four DB[a,l]PDE-14-N(6)dA adducts: (-)-anti-trans (26%), ()-anti-trans (26%), (-)-anti-cis (17%), and (+)-anti-cis (17%). The (+/-)-s yn-DB[a,l]PDE was reacted with dA under the same conditions to yield four D B[a,l]PDE-14-N(6)dA 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 of DB[a,l]PDE 14-N(6)dA were unequivocally assigned by reacting optically pure (-)-anti-D B[a,l]PDE and (+)-syn-DB[a,l]PDE with dA and by a combination of NMR, circu lar dichroism, and fast atom bombardment mass spectrometry. Reactions at 10 0 degrees C yielded mainly the trans-opened adducts at the benzylic C-14 po sition 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]PD E. Steric hindrance created by the fjord region may be an important factor for the stereoselectivity observed at room temperature.