En Route to Improved Antimalarial Peroxides Following the Natural Role Model Artemisinin

摘要

The synthesis of a series of 5-cyclopropyl substituted 1,2,4-trioxanes 3a-3f by a sequence of singlet oxygen ene reaction with the 1-cyclopropylated allylic alcohol 1 and subsequent peroxyacetalization reaction with aldehydes and ketones, respectively, is described. An important side reaction is the formation of cross-peroxyacetalization products 4 and 5 from the Lewis-acid catalyzed cleavage of the initially formed β-hydroperoxy alcohol 2. The in vitro antimalarial activities of several derivatives 3 against Plasmodium falciparum are remarkably high.