The chemical stability of S-(2-acylthioethyl) and S-acyloxymethyl protected thymidylyl-3',5'-thymidine phosphoromonothiolates and their deacylation products in aqueous solution.

The hydrolytic stability of the S-(2-acetylthioethyl) (1a,b), S-(2-pivaloylthioethyl) (2a,b), and S-acetyloxymethyl (3a,b) protected Rp and Sp phosphoromonothiolates of 3',5'-TpT has been studied. Rather unexpectedly, an intramolecular hydroxide ion catalyzed acetyl migration from the protecting group to the nucleoside 3'- and 5'-hydroxy functions was found to compete with the intermolecular displacement of the AcSCH2CH2S- or AcOCH2S-ligand from the phosphorus atom of 1a,b and 3a,b, respectively. With the S-pivaloylthioethyl derivative 2a,b no such reaction took place. Additionally, the kinetics of the cleavage of the S-(2-mercaptoethyl) group from 4a,b, the products of enzymatic deacylation of 1a,b and 2a,b, were studied as a function of pH.