Dioxolane nucleosides and their phosphonate derivatives: synthesis and hydrolytic stability

Abstract

Several new nucleoside (12–15) and nucleoside phosphonate (27–30) analogues derived from (±)-cis- and -trans-2-hydroxyrnethyl-4-methyl-1,3-dioxolane have been prepared and their configurations assigned by ¹H NMR spectroscopy. First-order rate constants for the acid-catalysed hydrolysis of the dioxolane ring have been determined at different hydronium ion concentrations. The phosphonate group accelerates the hydrolysis at pH > 2 by 2 orders of magnitude, while at pH < 1 the hydrolytic stabilities of the nucleoside analogues and their phosphonate derivatives are comparable. The possible reasons for this rate-enhancement are discussed on the basis of the reaction mechanism.