The photochemistry of 8-bromo-2′-deoxyadenosine. A direct entry to cyclopurine lesions

Abstract

The UV photolysis of 8-bromo-2′-deoxyadenosine has been investigated in different solvents and in the presence of additives like halide anions. Photolytic cleavage of the C–Br bond leads to formation of the C8 radical. In methanol, subsequent hydrogen abstraction from the solvent is the main radical reaction; however, in water or acetonitrile intramolecular hydrogen abstraction from the sugar moiety, to give the C5′ radical, is the major path. This C5′ radical undergoes a cyclization reaction on the adenine and gives the aminyl radical. A rate constant of 1.8 × 10⁵ s⁻¹ has been measured by laser flash photolysis in CH₃CN for this unimolecular process. Product studies from steady-state photolysis in acetonitrile have shown the conversion of 8-bromo-2′-deoxyadenosine to 5′,8-cyclo-2′-deoxyadenosine in 65% yield and in a diastereoisomeric ratio (5′R) ∶ (5′S) = 1.7. Evidence supporting that the equilibrium Br˙ + Br⁻ ⇌ Br₂˙⁻ plays an important role in this synthetically useful radical cascade is obtained by regulating the relative concentrations of the two reactive oxidizing species.