SYNTHESIS OF L-DIOXOLANE NUCLEOSIDES AND RELATED CHEMISTRY

(+)-L- or -(hydroxymethyl)-1,3-dioxolan-2-yl]-5-fluorouracil (25) and other novel classes of 1,3-dioxolane nucleosides have been synthesized . Coupling of (tert-butyldiphenylsilyl)oxy]methyl]-1,3-dioxolane (23) or 2-methyl-1,3-dioxolane (9) with silylated g-fluorouracil, thymine, cytosine, and 5-chlorocytosine in the presence of TMSOTf gave the corr esponding 1,3-dioxolane nucleosides. These nucleosides were decomposed and rearranged to the ring-opened products in certain reaction condit ions. It was found that 5-fluorouricil nucleosides (12 and 25) were re latively more stable than the thymine or cytosine derivatives (10, 13, and 16). Bulky protecting group (TBDPS) at the 1,3-dioxolane moiety i n compound 24 may also contribute the stability to the 1,3-dioxolane n ucleosides. The structures of these novel 1,3-dioxolane nucleosides an d ring-opened products have been assigned by NMR spectra, and the mech anisms of decomposition and rearrangement to the ring opened products were discussed.