Stereochemistry and antimalarial activity of C-10 carba analogues of artemisinin

Abstract

Artemisinin is an endoperoxide bond-containing sesquiterpene lactone showing potent antimalarial effect as well as antitumor and antivirus activities. Inspired by this unique pharmacorphore, researchers around the world developed numerous Artemisinin derivatives. Among these derivatives, the C-10 carba analogues of artemisinin are frequently reported. However, the stereochemistry of C-10 carba analogues of artemisinin is overlooked and the corresponding mixture of stereoisomers are used. Herein, we reported for the first time stereochemistry and antimalarial activity of C-10 carba analogues of artemisinin. We employed two approaches to obtain the pure isomer of C-10 carba analogues and presented an interesting observation about their antimalarial activities. The minor isomer with large-sized substitute and S configuration at C-10 position had much lower antimalarial effect than the major isomer with R configuration. The study will shed light on the development of effective antimalarial drugs based on ART.

Keywords: Antimalarial; Artemisinin; Chiral separation; Epimer.