Antimalarially potent, easily prepared, fluorinated endoperoxides

Abstract

Three or four step chemical synthesis and in vitro antimalarial testing showed crystalline, thermally stable, bicyclic endoperoxides 3c and 4c to be potent antimalarials, having approximately 15% of the antimalarial activity of the clinically used, complex, sesquiterpene, lactone, natural product artemisinin (qinghaosu, 1). A novel mechanism involving reactive alkylating agents is proposed to account for the ability of endoperoxides 3c and 4c to kill malaria parasites.