Synthesis and thiolytic cleavage of S-acyl derivatives of 5-mercaptouracil and 5-mercapto-2′-deoxyuridine

Several S-acyl derivatives of both 5-mercaptouracil (MU) and 5-mercapto-2′-deoxyuridine (MUdR) were synthesized for the purpose of temporarily protecting the parent compounds from oxidation to the disulfides. These acyl derivatives were found to be stable to hydrolysis under neutral conditions but to undergo facile transacylation with aliphatic thiols, thus releasing the antimetabolites in their active forms. The rate of this thiolytic cleavage depends on the structure of the acyl group as well as on the pK_a and concentration of the thiols.