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

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 x 10(5) s(-1) has been measured by laser ash 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 Brdegrees + Br-reversible arrow) Br-2(.-) plays an important role in this synthetically useful radical cascade is obtained by regulating the relative concentrations of the two reactive oxidizing species