Mechanistic insights towards endoperoxide formation of artemisinin

Artemisinin, one of the topics of the Nobel Prizes in Medicine in 2015, and its derivatives have been used to treat malaria. A new study published in the Journal of Natural Products finds that the endoperoxide formation of artemisinin from dihydroartemisinic acid, its biosynthetic precursor, undergoes a mixed mechanism. The study, from the lab of Francis Yoshimoto at UTSA, used regioselectively deuterated dihydroartemisinic acid isotopologues to measure competitive intermolecular kinetic isotope effects in the formation of artemisinin. The supporting information file is over 500 pages!

Cool!


Journal of Natural Products paper

Unnatural aza-artemisinin analog syntheses

Hiroki Oguri and co-workers from the University of Tokyo have reported in JOC on the synthesis of some nitrogen-containing artemisinin analogs. One of their racemic aza-analogs had more potent activity than artesunate.

 

JOC paper

Dihydroartemisinic Acid to Artemisinin

Francis Yoshimoto and co-workers at the University of Texas at San Antonio (UTSA) have reported in the Journal of Natural Products on the synthesis of a dihydroartemisinic acid isotopologue, which was regioselectively deuterated at C-3, and in turn was used to measure the rate of nonenzymatic conversion to artemisinin. Artemisinin was the topic of the 2015 Nobel Prize in Medicine and the biosynthesis of the endoperoxide, which is responsible for its antimalarial activity, has been controversial. This paper is related to the spontaneous oxidation of dihydroartemisinic acid to artemisinin when a dried down sample of dihydroartemisinic acid was exposed to air. Funny enough, there is another article on the spontaneous oxidation of avermectin, which was the topic of the 2015 Nobel Prize in Medicine as well.

J. Nat. Prod. paper (Artemisinin)