Chemical and electro-chemical reduction of qinghaosu (artemisinin)

1,2,4-Trioxane is the essential segment of the new antimalarial agent qinghaosu 1, and hence its reduction is an important plausible process related to the bio-activity mode. An overview of its reduction and a careful examination of some reducing systems are presented herewith. Electrochemical reduction is a two-electron reduction, which is confirmed by the isolation of product deoxyqinghaosu. However, in the presence of a catalytic amount of Fe-II/III electrochemical reduction yields mainly the single-electron-reduction products, which are identified with the products from reduction of qinghaosu with one equivalent ferrous sulfate or a catalytical amount of Fe-II/III and excess of other reducing agents, such as ascorbic acid, or cysteine. These results mean that qinghaosu is reduced by ferrous ion and the resulting ferric ion is then reduced on the electrode to regenerate ferrous ion. In addition, qinghaosu could be reduced to deoxyqinghao by iodide, but not by bromide, and also could be reduced by the ascorbic acid-CuSO4 system to give free-radical reaction products.