C5'-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 conformation.
Navacchia
Maria Luisa
ML
ISOF, Consiglio Nazionale delle Ricerche, Via P. Godetti 101, 40129 Bologna, Italy.
Chatgilialoglu
Chryssostomos
C
Montevecchi
Pier Carlo
PC
D003500:Cyclization; D003839:Deoxyadenosines / Q000138:chemical synthesis*; D005609:Free Radicals; D006860:Hydrogen Bonding; D013237:Stereoisomerism
D003839:Deoxyadenosines; D005609:Free Radicals