Orally active, hydrolytically stable, semisynthetic, antimalarial trioxanes in the artemisinin family

In only three chemical operations, natural trioxane lactone artemisinin (1) was converted into a series of C-10 carbon-substituted 10-deoxoartemisinin compounds 4-9. The three steps involved lactone reduction, replacement of the anomeric lactol OH by F using diethylaminosulfur trifluoride, and final ly boron trifluoride-promoted substitution of F by aryl, heteroaryl, and ac etylide nucleophiles. All of these C-10 nonacetal, chemically robust, enant iomerically pure compounds 4-9 have high antimalarial potencies in vitro ag ainst Plasmodium falciparum malaria parasites, and furans 5a and 5b and pyr role 7a are antimalarially potent also in vivo even when administered to ro dents orally.