Adenosinyl Radical Cyclization. A Stereochemical Investigation

A variety of substituted 2?-deoxyadenosin-5?-yl radicals 3 were generated under different reaction conditions. Radicals 3 underwent intramolecular cyclization onto the C8-N7 double bond of the adenine moiety leading to aminyl radicals (5?S,8R)-4 and (5?R,8R)-4 and, eventually, to the corresponding cyclonucleosides 5 and 6. The effect of the solvent, the nature of the substituents, and the generation method of radicals 3 on the stereoselectivity of the C5?-radical cyclization have been considered. The observed increase of the (5?S)/(5?R) ratio by increasing the bulkiness of the R1 group is explained in terms of steric repulsion between R1 and the purine moiety which favors the C5?-endo conformation, whereas the effect of the water solvent in promoting the (5?R)-stereoselective cyclization is ascribed to intermolecular hydrogen bonding stabilizing the C5?-exo confomation.