Effects of Cyclonucleoside Formation on the Rates of Glycosidic Hydrolyses in Purine Ribonucleosides

Article abstract of DOI:10.1021/jo00390a028

Syntheses of several carbon-bridged purine cyclonucleosides are reported, along with kinetic data on their rates of glycosidic hydrolysis.We find that 5',8-bridged nucleosides hydrolyze less than 10 times more slowly than analogous nucleoside models, but that the 3,5'-bridged adenosine hydrolyzes 29000 times more slowly than does 3-methyladenosine at 25 deg C in 0.1 N HCl.This surprising stability can be rationalized on the basis of (1) an electrostatic effect resulting from the presence of an ammonium group at the 5'-carbon and (2) the existence of a nonideal geometry for lone-pair stabilization of the transition structure.On the basis of these results, the previously reported slow rates of hydrolysis in 3,5'-cycloguanosine and 3,5'-cyclowyosine can be rationalized