Mechanism-based design of simple, symmetrical, easily prepared, potent antimalarial endoperoxides

Abstract

Mechanism-based design, two-step synthesis, and in vitro antimalarial testing showed thermally stable, crystalline, bicyclic endoperoxides 2a and 2b to be potent antimalarials. Their reduction by FeBr2 proceeds via oxy-radicals and then carbon radicals that undergo β-scission to form an alkene and a high-valent FeO species.