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A masked combination chemotherapy which relies on the embedding of a number of active components, in a latent form, within a single endoperoxidic chemical entity is the aim of the research presented. The approach is illustrated by means of purposely designed bicyclic endoperoxide prodrug prototypes 1 and subsequently validated through the study of model compounds 2 (Ar=Ph, p‐FC6H4, p‐ClC6H4).

An optimised protocol has been developed for the coupling of dihydroartemisinin benzoate with a range of aromatic allylsilanes to provide a number of new C-10 deoxo derivatives (11a-11g) in yields ranging from 70 to 94%. These compounds were up to ten times more potent than artemisinin in in vitro tests against the chloroquine resistant K1 strain of Plasmodium falciparum. Ferrous mediated degradation of these analogues produces as the main product, a dicarbonyl formate 12, which is not seen when the same reaction is carried out with artemisinin or artemether. This finding may indicate that analogues in this class have a subtly different "antimalarial" mechanism of action.

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