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