Synthesis and antiviral activity of oxaselenolane nucleosides

As dioxolane and oxathiolane nucleosides have exhibited promising antiviral and anticancer activities, it was of interest to synthesize isoelectronica lly substituted oxaselenolane nucleosides, in which the 3'-CH2 is replaced by a selenium atom. To study structure-activity relationships, various pyri midine and purine oxaselenolane nucleosides were synthesized from the key i ntermediate, (+/-)-2-benzoyloxymethyl-1,2-oxaselenolane 5-acetate (6). Amon g the synthesized racemic nucleosides, cytosine and 5-fluorocytosine analog ues exhibited potent anti-HIV and anti-HBV activities. It was of interest t o obtain the enantiomerically pure isomers to determine if they have differ ential antiviral activities. However, due to the difficult and time-consumi ng nature of enantiomeric synthesis, a chiral HPLC separation was performed to obtain optical isomers from the corresponding racemic mixtures. Each pa ir of enantiomers of Se-ddC and Se-FddC was separated by an amylose chiral column using a mobile phase of 100% 2-propanol. The results indicate that m ost of the anti-HIV activity of both cytosine and fluorocytosine nucleoside s resides with the (-)-isomers.