FIGURE 1.

Artemisinin, clinical derivatives dihydroartemisinin (DHA), artemether, artesunate and the amino-artemisinins artemiside and artemisone. Artemether and artesunate are rapidly converted into DHA in vivo via facile metabolism or hydrolysis respectively. As a hemiacetal, DHA is intrinsically unstable, and rearranges irreversibly under physiological conditions into a peroxyhemiacetal that in turn rearranges to the inert deoxyartemisinin. In contrast, the amino-artemisinins do not provide DHA on metabolism.