Syntheses of the two artemisinin tricyclic analogs 39 and 40 and 40 by ozonization. These trioxanes were thus synthesized by a linear sequence of seven chemical bearing a methyl group at C-5a have been accomplished. The common starting material in both approaches was operations, with an overall yield of ca. 9% and 11%, respectively, from 2-methylcyclohexanone (8). Both enantiomerically pure oxo nitrile (R)-10 which was elaborated through the Michael addition of chiral imine 9 to compounds proved to be completely devoid of antimalarial activity on the "H" clone of Plasmodium falciparum. In acrylonitrile. Several strategies for converting 10 into targets 39 and 40 were investigated. The strategy which was contrast, the two structural analogs 43 and 44 having a hydrogen atom at the C-5a angular position display relatively ultimately adopted employed the addition of [chloro(trimethylsilyl)methyl]lithium (15) to 10. The resulting high antimalarial activities. Thus, the fact that the replacement of the hydrogen atom at C-5a by a methyl group epoxysilane 16 was converted into vinylsilane 36 by an original route involving first the regioselective opening of the in tricyclic trioxanes 6 was detrimental to biological activity reinforced the hypothesis that tight hemin-trioxane oxirane ring by means of HBr, followed by zinc reduction. Addition of methyllithium to form 36 furnished pivotal complexes of type 7 are involved in the activation phase of these antimalarial agents. derivative 37 which was finally converted into our targets 39