Synthesis of novel 2'-spirocyclopropyl-5'- deoxyphosphonic acid furanosyl nucleoside analogues as potent antiviral agents.

Novel 5'-deoxyfuranosyl purine phosphonic acid analogues with 2 '-electropositive moiety, such as spirocyclopropanoid, were designed and synthesized from commercially available diethyl malonate. Condensation reaction successfully proceeded from a glycosyl donor 15 at low reaction temperature in Vorbruggen conditions to give desired phosphonate analogues 16b and 23b. The synthesized nucleotide analogues 19, 22, 26, and 29 were subjected to antiviral screening against HIV-1. Adenine phosphonic acid analogue 22 shows significant anti-HIV activity (EC(50) = 7.9 μM).