Synthesis of chemoreversible prodrugs of ARA-C

The synthesis of N⁴-peptidyl- derivatives of ara-C (1) is described. In these derivatives, the active drug is released by an intramolecular cyclization process with formation of a six-membered heterocycle. No enzymatic or solvolytic conversion is necessary. NMR studies of the rates of cyclization is basic and acidic environment are discussed.