Kinetics for the acid-catalysed hydrolysis of O-, S- and N-bridged 5′,8-cyclonucleosides related to adenosine

Abstract

Kinetics of the acid-catalysed hydrolysis of O^5′,8-cycloadenosine, S^5′, 8-cyclo-5′-thioadenosine and N^5′, 8-cyclo-5′-amino-5′-deoxyadenosine have been studied. The S- and N-bridged cyclonucleosides are hydrolysed exclusively by the rupture of the N-glycosidic bond, while the O-bridged compound undergoes concurrent cleavage of the N-glycosidic and 5′,8-cyclo linkages, the proportion of the former reaction being markedly increased with increasing temperature. The conformations of the same cyclonucleosides have been elucidated by molecular modelling (SYBYL) and ¹H NMR spectroscopy. The effect of the sugar ring puckering on the hydrolytic stability is discussed.