C5′-adenosinyl radical cyclization. A stereochemical investigation

Article abstract of DOI:10.1021/jo060197z

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.