Total Synthesis of Penicinoline E, Marinamide, Methyl Marinamide and their Antimalarial Activity

Abstract

Syntheses of unusual pyrrole alkaloids Penicinoline E, Marinamide and Methyl marinamide were successfully achieved in two steps from easily accessible starting materials with excellent overall yields 70–97 %. The Suzuki-Miyaura coupling followed by dearomatization represents the key step in the synthesis of title compounds. The structure of Penicinoline E was unequivocally confirmed by single X-ray analysis. The antiplasmodial activity of alkaloids was evaluated and shown a good antimalarial activity against human malaria parasite Plasmodium falciparum in vitro. Against chloroquine sensitive (pf3d7), both Penicinoline E and Methyl marinamide displayed IC50 value of 1.56 μM and Marinamide displayed IC50 value of 25 μM respectively. In addition, against chloroquine resistant strain (pfDd2) of plasmodium falciparum they have also shown 4.68 μM, 2.34 μM and 25 μM respectively.