Four-step synthesis of the antimalarial cardamom peroxide via an oxygen stitching strategy

Abstract

A four-step synthesis of the antimalarial terpene cardamom peroxide, a 1,2-dioxepane-containing natural product, is reported from (-)-myrtenal and molecular oxygen. This highly concise route was guided by biosynthetic logic and enabled by an unusual manganese-catalyzed, tandem hydroperoxidation reaction. The absolute configuration of the cardamom peroxide is reported, and its mode of fragmentation following Fe(II)-mediated endoperoxide reduction is established. These studies reveal the generation of reactive intermediates distinct from previously studied endoperoxide natural products. © 2014 American Chemical Society.