Hydrolytic dethiophosphorylation and desulfurization of the monothioate analogues of uridine monophosphates under acidic conditions

Abstract

The hydrolytic reactions of uridine 2′-, 3′- and 5′-phosphoromonothioates (2″-, 3′- and 5′-UMPS) under acidic and neutral conditions have been followed by HPLC. Under slightly acidic conditions (pH 2–5), only pH-independent dethiophosphorylation to uridine takes place. This reaction is 200- to 300-fold as fast as dephosphorylation of the corresponding uridine monophosphates (UMP), presumably due to higher stability of the thiometaphosphate monoanion compared to metaphosphate anion. At pH > 5, i.e. at pH > pK_a2 of the thiophosphate moiety, the dethiophosphorylation is retarded with increasing basicity of the solution. At pH < 1, acid-catalysed desulfurization of 2′- and 3′-UMPS to an isomeric mixture of 2′/3′-UMP competes with their dethiophosphorylation. This reaction is suggested to proceed by a nucleophilic attack of the neighbouring hydroxy group on phosphorus. No such reaction occurs with 5′-UMPS. In contrast to 2′- and 3′-UMP, no sign of interconversion of 2′- and 3′-UMPS is detected.