Diastereoselective Synthesis of (1,3-Dioxan-4-yl)pyrimidine and Purin Nucleoside Analogues

(1,3-Dioxan-4-yl)-substituted nucleoside analogues, higher homologues of antiviral and anticancer 1,3-dioxolanes, were prepared from the key intermediate (4-acetoxy-1,3-dioxan-2-yl)methyl benzoate and silylated bases. Glycosylation, carried out under Vorbrüggen conditions in the presence of trimethylsilyltrifluoromethanesulfonate (TMSOTf) as a catalyst, afforded the desired compounds with high stereoselectivity and regioselectivity, with only the desired β-anomeric N-1 pyrimidine and N-9 purin nucleosides being obtained. 1H NMR experiments established that the β-anomers were diequatorial, and this assignment was confirmed by singlecrystal X-ray diffraction. Despite their structural similarities with natural nucleosides, none of the synthesized nucleosides showed antiviral activity.