DIOXOLANE NUCLEOSIDES AND THEIR PHOSPHONATE DERIVATIVES - SYNTHESIS AND HYDROLYTIC STABILITY

Several new nucleoside (12-15):and nucleoside phosphonate (27-30) anal ogues derived from (+/-)-cis-and -trans-2-hydroxymethyl-4-methyl-1,3-d ioxolane have been prepared and their configurations assigned by H-1 N MR spectroscopy. First-order rate constants for the acid-catalysed hyd rolysis of the dioxolane ring have been determined at different hydron ium ion concentrations. The phosphonate group accelerates the hydrolys is at pH > 2 by 2 orders of magnitude, while at pH < 1 the hydrolytic stabilities of the nucleoside analogues and their phosphonate derivati ves are comparable. The possible reasons for this rate-enhancement are discussed on the basis of the reaction mechanism.