Hydrolysis and intramolecular transesterification of ribonucleoside 3′-phosphotriesters: the effect of alkyl groups on the general and specific acid–base-catalyzed reactions of 5′-O-pivaloyluridin-3′-yl dialkyl phosphates

Abstract

Diisopropyl, diethyl, bis(2-methoxyethyl) and isopropyl 2-methoxyethyl esters of 5′-pivaloyl-2′-(tetrahydropyran-2-yl)uridin-3′-yl phosphate have been prepared. The 2′-protecting group has been removed under acidic conditions, and the isomerization of the resulting ribonucleoside 3′-phosphotriester to its 2′-counterpart and the cleavage of the isomeric mixture to 2′- and 3′-phosphodiesters and a 2′,3′-cyclic phosphate has been followed by reverse phase HPLC in aqueous hydrogen chloride and several buffer solutions over a wide acidity range from H₀ – 1.5 to pH 8. The β_lg values of the buffer-independent partial reactions, and the β_lg and Brønsted α and β values of the buffer catalyzed reactions have been determined. The mechanisms of various partial reactions are discussed on the basis of the structural effects observed.