Total synthesis of cyclotheonamide C by use of an alpha-keto cyanophosphorane methodology for peptide assembly

Stéphane Roche (1) , Sophie Faure (1) , Lahssen El Blidi (1) , D.J. Aitken (2)

1 SEESIB - Synthèse et étude de systèmes à intêret biologique
2 ICMMO - Institut de Chimie Moléculaire et des Matériaux d'Orsay

The total synthesis of cyclotheonamide C (3), a macrocyclic pentapeptide incorporating an alpha-keto homoarginine (k-Arg) and a vinylogous dehydrotyrosine (V-deltaTyr) unit, has been achieved. For comparison of macrocyclisation feasibility, two linear pentapeptides bearing free ketone functions at the k-Arg units were prepared, by use of tandem oxidation/coupling reactions on alpha-keto cyanophosphorane precursors as the key processes for pentapeptide elaboration. Successful activation and coupling at the pentapeptide V-deltaTyr C terminus led to the target molecule core, and thus provided a short total synthesis of the target compound

Domaines: Chimie organique

Stéphane Roche, Sophie Faure, Lahssen El Blidi, D.J. Aitken. Total synthesis of cyclotheonamide C by use of an alpha-keto cyanophosphorane methodology for peptide assembly. European Journal of Organic Chemistry, 2008, pp.5067-5078. ⟨hal-00327190⟩