Dispiro N-Boc-protected 1,2,4-trioxane 2 was synthesised via Mo(acac)(2)
catalysed perhydrolysis of N-Boc spirooxirane followed by condensation of
the resulting beta-hydroperoxy alcohol 10 with 2-adamantanone. N-Boc
1,2,4-trioxane 2 was converted to the amine 1,2,4-trioxane hydrochloride
salt 3 which was subsequently used to prepare derivatives (4-7). Several of
these novel 1,2,4-trioxanes had nanomolar antimalarial activity versus the
3D7 strain of Plasmodium falciparum. Amine intermediate 3 represents a
versatile derivative for the preparation of achiral arrays of trioxane analogues
with antimalarial activity.