Synthesis and Structure Determination of the Adducts of Dibenzo[a,l]pyrene Diol Epoxides and Deoxyadenosine or Deoxyguanosine

Abstract

(±)−Syn−dibenzo[a,l]pyrene diol epoxide (DB[a,l]PDE) and (±)−anti−DB[a,l]PDE were reacted with deoxyadenosine (dA) or deoxyguanosine (dG) in dimethylformamide at 100 °C for 30 min. The crude products were purified by reverse phase HPLC under gradient and isocratic conditions. The structure of each adduct was assigned by 1D and 2D NMR spectra and by fast atom bombardment mass spectrometry. Five adducts were isolated from the reaction of (±)−syn−DB[a,l]PDE and dA: syn−DB[a,l]PDE−N⁶dA−1, syn−DB[a,l]PDE−N⁶dA−2, syn−DB[a,l]PDE−N⁶dA−3, syn−DB[a,l]PDE−N⁶dA−4 and syn−DB[a,l]PDE−N7Ade. Four adducts were isolated from the reaction of (±)−anti−DB[a,l]PDE and dA: anti−DB[a,l]PDE−N⁶dA−1, anti−DB[a,l]PDE−N⁶dA−2, anti−DB[a,l]PDE−N⁶dA−3 and anti−DB[a,l]PDE−N⁶dA−4. Two adducts were isolated from the reaction of (±)−syn−DB[a,l]PDE and dG: (±)−11,12,13−trihydroxy−tetrahydroDB[a,l]P−14−N²dG and (±)−11,12,13−trihydroxy−tetrahydroDB[a,l]P−14−N7Gua. Two adducts were isolated from the reaction of (±)−anti−DB[a,l]PDE and dG: (±)−11,12,13−trihydroxy−tetrahydroDB[a,l]P−14−N²dG and (±)−11,12,13−trihydroxy−tetrahydroDB[a,l]P−14−N7Gua.

Key Words:

• Dibenzo[a,l]pyrene
• diol epoxides
• deoxyribonucleoside adducts
• synthesis
• structure determination