Artemisinin is a natural product isolated from the plant Artemisia annua that is currently the fastest-acting treatment available against Plasmodium falciparum—the protozoan parasite that causes the deadliest form of malaria. The low bioavailability of this compound and its short half-life, however, make the cost of artemisinin therapies very high. Anti-malarial combination therapies involving artemisinin are employed to avoid the development of resistance to the drug by the parasite, as recommended by the World Health Organization. Artemisinin’s structure contains a unique peroxide bridge that is believed to be responsible for the drug’s mechanism of action. Recent reports show that artemisinin binds covalently to a large number of proteins after being “activated” most likely by heme, which builds up in the parasite cells given its ‘blood-eating’ nature. We gather that the exceptional biological activity of this compound may originate in the fine-tuned chemical reactivity of its peroxide bridge, rather than the topology of the structure itself. Consequently, we hypothesize that its enantiomer (ent-artemisinin)—a yet unreported compound, to the best of our knowledge—could exhibit comparable anti-malarial properties. Seeking an affordable synthetic route, our current goal is to develop a reaction sequence to produce ent-artemisinin from zingiberene, a compound found in ginger oil. If successful, we believe that the low cost and high availability of ginger oil would allow for the large-scale production of ent-artemisinin.

Studies toward the synthesis of ent-artemisin: A potential anti-malarial compound

254th National Meeting (2017)

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