Artemether

Artemisinin is a venerable malaria drug that was introduced more than 40 years ago. It was the Molecule of the Week for December 12, 2005.

Artemisinin is an excellent remedy for malaria. For many years, however, its supply has been unpredictable. The sole source of the drug is the sweet wormwood plant (Artemisia annua) that grows in Southeast Asia; but its production cycle is vicious. Farmers grow the plant only when prices are high; the inevitable oversupply lowers prices and production drops, raising prices again.

As a result, medicinal researchers sought to synthesize an artemisinin precursor that would ensure a constant supply of the drug at lower cost than agricultural artemisinin. Sanofi (Gentilly, France) developed a synthesis of artemether (Figure 1), which it commercialized in 2013. Unfortunately, the project failed because the semisynthetic artemisinin could not be produced less expensively than the farmed product.

Since then, drug researchers concentrated on improving the yield of artemisinin and its derivatives from A. annua. For example, the leaves of the plant contain as much dihydroartemisinic acid (DHAA) as artemisinin. Earlier this year, Kerry Gilmore and Peter H. Seeberger at Max Planck Institute of Colloids and Interfaces (Potsdam, Germany) reported that crude extracts of A. annua can be fed into a photochemical flow reactor to produce artemisinin, artemether, and a third active pharmaceutical ingredient, artesunate (Figure 2).

Artesunate turns out to be a particularly attractive malaria drug. It is much more water-soluble than artemisinin, so it can be taken by mouth* or by injection. It is safe and well-tolerated by adults and children. Its success has earned it a place in the World Health Organization's List of Essential Medicines.

*But overdoses can be harmful; see hazard information table.