A new decomposition product of dihydroartemisinin

Artemisinin is a natural product with antimalarial properties that originates from the plant Artemisia annua. It can chemically be reduced to dihydroartemisinin, which was reported to be more active than the parent compound and which serves as a precursor for the antimalarial drugs artesunate and artemether [1,2]. After prolonged storage, samples of dihydroartemisinin were found to contain a decomposition product with a molecular weight of 238, the formation of which was accelerated by heating at 60°C for several days. This decomposition product was isolated and identified as 2-(3-oxobutyl)-3-methyl-6-(2-propanal)-cyclohexanon, known to be formed by thermolysis of dihydorartemisinin at 190°C [3]. However, during work-up of this compound a hitherto unknown decomposition product of dihydroartemisinin with a molecular weight of 210 was obtained and identified by ¹H, ¹³C and 2D NMR spectroscopy as 2-(3-oxobutyl)-3-methyl-6-ethyl-cyclohexanone. This new degradation product can be formed by oxidation and subsequent decarboxylation of the former decomposition product.

2-(3-oxobutyl)-3-methyl-6-ethyl-cyclohexanon

References: [1] Sriram, D. et al. (2004) Nat Prod Research 18: 503–527. [2] Meshnick, S.R. et al. (1996) Microbiol Rev 60: 301–315. [3] Lin, A.J. et al. (1986) Tetrahedron 42: 2181–2184.