An efficient route into synthetically challenging bridged achiral 1,2,4,5-tetraoxanes with antimalarial activity

Here we present an efficient route into synthetically challenging bridged 1,2,4,5-tetraoxanes. The key to the success of this route is the use of H2O2 and catalytic I2 to form the gem-dihydroperoxide followed by a Ag2O mediated alkylation using 1,3-diiodopropane. Using this methodology a range of bridged tetraoxanes which display good in vitro antimalarial activity were synthesized.