Abstract: Actinomycin D(AMD) is well known for its specific inhibition of DNA transcription, and has been used clinically as an antitumor drug for the treatment of some highly malignant tumors. Based on the former research, two [D-Phe²]₂AMD analogs with L-MeVal(the fifth amino acid residue in the cyclic depsipeptide of AMD) substituted by D-MeVal and D-MePhe were designed to reduce the toxicity and increase the antitumor activity. Another analog in which the D-Val residue replaced with D-MeVal was designed to eliminate or to weaken the hydrogen bonds of D-Val residues between α and β rings. All three novel compounds were prepared from C terminal to N terminal in solution phase to form linear pentapeptides, and cyclized by BOP-Cl/Et³N in DCM. Condensation of pentapeptide lactone with BMNBCA, followed by catalytic reduction, controlling oxidation by K₃Fe(CN)₆ and purification afforded the analogs as red solid. The spectrum data of all three analogs including HR-MS, ¹H NMR and [α] D were given.

Key words: Actinomycin D, Analogs, Total chemical synthesis