THE DEOXYGENATION AND ISOMERIZATION OF ARTEMISININ AND ARTEMETHER ANDTHEIR RELEVANCE TO ANTIMALARIAL ACTION

The treatment of artemisinin (1) and beta-artemether (6) with Zn disso lving in AcOH for a few hours results in mono-deoxygenation giving deo xyartemisinin (5) and deoxy-P-artemether (7), respectively, as the sol e product. In contrast, submission of 1 to FeCl2 . 4 H2O in MeCN at ro om temperature for 15 min causes only isomerization, -dimethyl-8-oxo-2 H,10H-furo[3,2-i]benzopyran-10-yl acetate (8) and (3R)-3-hydroxydeoxya rtemisinin (9) being produced in 78 and 17% yield, respectively. The a ction of FeCl2 . 4 H2O in MeCN on 6 is similar. Under the same conditi ons, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of thyl-2-oxo-3-(3-oxobutyl)cyclohexyl]propanaldehyde in yield s of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygena tion of 1 and 6 by Zn is rationalized in terms of its oxophilic nature . The catalyzed isomerization of 1 and 6 by Fe2+ is attributed to the redox properties of the Fe2+/Fe3+ system.