Synthesis and antiviral evaluation of 1,4-dioxane nucleoside analogues related to nucleoside dialdehydes

Since biologically active nucleoside 2',3'-dialdehydes exist as six-membered cyclic acetals (1) in solution, we have investigated the antiviral activity of some structurally similar 1,4-dioxane nucleoside analogues. By reacting 2',3'-seconucleoside tosylates with base, the guanine (10) and adenine (18) substituted (hydroxymethyl)dioxanes have been constructed. In addition, an unusual adenine-substituted divinyl ether (22) was synthesized via a base-catalyzed, double elimination of a 2',3'-di-O-tosyl-2',3'-secoadenosine. None of these compounds showed significant antiviral activity.