HYDROLYSIS OF DIDEOXYGENATED PURINE NUCLEOSIDES - EFFECT OF MODIFICATION OF THE BASE MOIETY

Dideoxynucleosides are receiving a considerable amount of interest currently because of their ability to inhibit the cytopathic effect of the human immunodeficiency virus (HIV-1), the etiologic agent of AIDS.2-5 Dideoxyadenosine (ddA) and dideoxyinosine (ddI), members of this class of nucleosides, have potent activity against the AIDS virus and are currently undergoing extensive biological and clinical studies.5-9 However, both ddA and ddI are unstable with respect to hydrolytic cleavage of the glycosidic bond.10 This inherent factor limits considerably the usefulness of these compounds as biological probes and antiviral agents. The design of congeners that would be more stable hydrolytically than the parent compounds would be of considerable significance in this area. However, the rational design of such new analogues requires some information on the effect of structural modification on hydrolytic stabilities. Although the hydrolytic stabilities of ribonucleosides have received considerable attention,11-15. © 1990, American Chemical Society. All rights reserved.