In simulated stomach acid (aqueous 0.01 M HCl, 37-degrees-C) beta-arte
ether decomposed (half-life, 441 +/- 17 min) to dihydroartemisinin, wh
ich subsequently rearranged to a new compound (1) having an endoperoxi
de group and an aldehyde group. The in vitro antimalarial activity of
dihydroartemisinin is similar to that of beta-arteether, whereas compo
und 1 had approximately 1/10th the activity of beta-arteether. Compoun
d 1 was prepared in sufficient quantities to afford samples for biolog
ical evaluation and a complete chemical characterization with H-1- and
C-13-NMR and mass spectrometry. While beta-arteether would be somewha
t unstable in the stomach, if the drug were administered on an empty s
tomach (emptying time, almost-equal-to 30 min) as a suspension or tabl
et, sufficient quantities of intact arteether may reach the small inte
stines, where it would be stable and readily absorbed. Its decompositi
on products, dihydroartemisinin and 1, may also contribute to the anti
malarial activity of the administered drug following oral administrati
on.