Replacement of the nonperoxidic trioxane oxygen atom of artemisinin by carbon: Total synthesis of (+)-13-carbaartemisinin and related structures

Abstract Provided by total synthesis, endoperoxides 17 , 19 and 21 underwent intramolecular oxymercuration-demercuration leading respectively to formation of an isomeric tetracycle, (1aS,3S,5aS,6R,8aS,9R,12S)-10-deoxo-13-carbaartemisinin 18 , (+)-10-deoxo-13-carbaartemisinin 20 , and (+)-13-carbaartemisinin 4 . Neither target 4 nor 20 displayed substantial antimalarial potency in vitro against Plasmodium falciparum , but the isomeric peroxide 18 possessed reasonable antimalarial potency in vitro .