Synthesis of C-4’Truncated Phosphonated Carbocyclic 2’-Oxa-3’-azanucleosides as Antiviral Agents

Anew template of C-40-truncated phosphonated nucleosides (TPCOANs) has been obtained in good yields according to two different routes which exploit the reactivity of a phosphonated nitrone. The one-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl nucleobases leads to the unnaturalR-nucleosides as themain adducts.On the other hand, the target β-anomers have been obtained in high yield by a two-step procedure based on the 1,3-dipolar cycloaddition of a phosphonated nitrone with vinyl acetate followed by nucleosidation reaction. The reactivity of the phosphonated nitrone has been investigated trough quantummechanicalDFT calculations at the B3LYP/D95þ(d,p) theory level. Preliminary biological assays show that β-anomers of TPCOANs are able to inhibit the reverse trancriptase of different retroviruses at concentrations in the nanomolar range, with a potency comparable with that of tenofovir