Antimalarial sulfone trioxanes

Abstract

A series of new sulfide and sulfone 1,2,4-trioxanes was prepared in only a few steps from commercial reactants. The sulfone trioxanes were found to have higher in vitro antimalarial potencies than the sulfides, with 12β-arylsulfone trioxanes 1β being from 13 to 14 as potent as the complex natural antimalarial trioxane artemisinin (2). A tentative chemical mechanism is proposed to account for the great difference in antimalarial activity of the 12α- vs. 12β-sulfide trioxanes.