Synthesis and anti-HIV activity of l-2′,3′-Dideoxy-4′-selenonucleosides (l-4′-Se-ddNs)

Based on the potent anti-HIV activity of l-2′,3′-dideoxycytidine (l-ddC), l-2′,3′-dideoxy-4′-selenonucleosides (l-4′-Se-ddNs) have been synthesized from natural chiral template, l-glutamic acid, using Pummerer-type condensation as a key step. All synthesized compounds were assayed for anti-HIV-1 activity, but none of them did show any significant antiviral activity up to 100 μM, probably due to conformational differences between l-ddC and l-4′-Se-ddC, induced by the bulky selenium atom, which might play an important role in phosphorylation by cellular kinase.