The Deoxygenation and Isomerization of Artemisinin and Artemether and Their Relevance to Antimalarial Action

✍ Scribed by Charles W. Jefford; Maria G. H. Vicente; Yvan Jacquier; France Favarger; Jiri Mareda; Patricia Millasson-Schmidt; Gerhard Brunner; Ulrich Burger

• Publisher: John Wiley and Sons
• Year: 1996
• Tongue: German
• Weight: 854 KB
• Volume: 79
• Category: Article
• ISSN: 0018-019X
• DOI: 10.1002/hlca.19960790520

✦ Synopsis

Abstract

The treatment of artemisinin (1) and β‐artemether (6) with Zn dissolving in AcOH for a few hours results in mono‐deoxygenation giving deoxyartemisinin (5) and deoxy‐β‐artemether (7), respectively, as the sole product. In contrast, submission of 1 to FeCl~2~ · 4 H~2~O in MeCN at room temperature for 15 min causes only isomerization, (3a__S__,4__R__,6a__S__,7__R__,10__S__,10a__R__)‐octahydro‐4,7‐dimethyl‐8‐oxo‐2__H__‐10__H__‐furo[3,2‐i] benzopyran‐10‐yl acetate (8) and (3__R__)‐3‐hydroxydeoxyartemisinin (9) being produced in 78 and 17% yield, respectively. The action of FeCl~2~ · 4 H~2~O in MeCN on 6 is similar. Under the same conditions, 6 gives products analogous to 8 and 9 accompanied by an epimeric mixture of 2‐[4‐methyl‐2‐oxo‐3‐(3‐oxobutyl)cyclohexyl]propanaldehyde in yields of 32, 23, and 16%, respectively. No epoxide is formed on repeating the last two experiments in the presence of cyclohexene. The deoxygenation of 1 and 6 by Zn is rationalized in terms of its oxophilic nature. The catalyzed isomerization of 1 and 6 by Fe^2+^ is attributed to the redox properties of the Fe^2+^/Fe^3+^ system.