Chemical transformations of artemisinin

Abstract

Artemisinin is a metabolite of the plant Artemisia annua L. This sesquiterpene lactone exhibits antimalarial activity and is commercially available. Various derivatives and analogues of this compound are potent agents exhibiting a wealth of biological activities and used as efficient drugs in clinical practice. The review is devoted to the chemical reactions of artemisinin and its best known derivatives (artemisitene, dihydroartemisinin, anhydrodihydroartemisinin), whose molecular structures retain the tetracyclic skeleton with the peroxide bridge. Main methods for structure modification of their molecules under the action of various oxidizing and reducing agents, acids and bases, electrophiles and nucleophiles are described. Catalytic reactions, as well as enzymatic, and photochemical transformations of artemisinin and its analogues are considered. Reactions occurring with preservation of the tetracyclic peroxide skeleton, as well as ring rearrangement and degradation of one or more rings are analyzed. Most transformations were shown to afford biologically active products.