Diversification in the synthesis of antimalarial trioxane and tetraoxane analogs

Artemisinin and its semi synthetic analogs have established themselves as effective antimalarial drugs. Since artemisinin is naturally isolated, in short supply and is very expensive to synthesize, extensive research on the discovery of peroxidic antimalarial compounds has intrigued scientists to explore structurally simple yet diverse cyclic peroxides. Consequently, trioxanes and tetraoxanes have been identified as promising candidates for the development of the next generation of antimalarial drugs. To combine the latest synthetic routes and methodologies employed in their synthesis along with earlier reports (dating back to 1899), we present an integrated overview on the diversified synthesis of trioxanes, tetraoxanes and their hybrids.