Mutual isomerization of uridine 2′- and 3′-alkylphosphates and cleavage to a 2′,3′-cyclic phosphate: the effect of the alkyl group on the hydronium- and hydroxide-ion-catalyzed reactions

Abstract

Isopropyl, ethyl, 2-ethoxyethyl, 2-chloroethyl, 2,2-dichloroethyl and 2,2,2-trichloroethyl esters of uridine 3′-phosphate have been prepared. In aqueous acid the compounds undergo concurrent isomerization to 2′-alkylphosphates and cleavage to uridine 2′,3′-cyclic phosphate, but in aqueous alkali only cleavage to the cyclic phosphate takes place. Buffer-independent rate constants for these reactions have been determined. The hydroxide-ion-catalyzed reaction to the 2′,3′-cyclic monophosphate is exceptionally susceptible to the polar nature of the leaving group, the β_1g value being –1.28 ± 0.05. By contrast, the hydronium-ion-catalyzed isomerization and cleavage are both rather insensitive to the electron-withdrawing ability of the alkyl group, the β and β_1g values being –0.18 ± 0.02 and –0.12 ± 0.05, respectively. The transition state structures of the reactions are discussed on the basis of these structural effects.