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

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 H-0 - 1.5 to pH 8. The beta(1g) values of the buffer-independent partial reactions, and the beta(1g) and Bronsted alpha and beta 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.