Jozimine A (‘dimeric’ dioncophylline A), a non-natural michellamine analog with high antimalarial activity

Abstract

Abstract The synthesis of jozimine A, the first non-natural dimer of a naturally occurring monomeric naphthylisoquinoline alkaloid, is described, starting from dioncophylline A, as isolated from Triphophyllum peltatum , resp. prepared by total synthesis. It is the first dimeric naphthylisoquinoline alkaloid that displays distinct antimalarial activity (IC 50 = 0.075 μg/ml) against asexual erythrocytic stages of Plasmodium falciparum , which even exceeds the activity of its monomeric precursor, dioncophylline A (IC 50 = 1.44 μg/ml), and thus constitutes a novel type of antimalarial quateraryls.