Synthetic methods for unsymmetrically-substituted 1,2,4,5-tetroxanes and of 1,2,4,5,7-pentoxocanes

Ozonolysis of vinyl ethers 1a-e in the presence of hydrogen peroxide in diethyl ether gave the corresponding 1,1-bis(hydroperoxide)s 2a-c. Subsequent trimethylsilylation, followed by the TMSOTf-catalyzed cyclocondensation with carbonyl compounds gave the unsymmetrically-substituted 1,2,4,5-tetroxanes 5-14. Similarly, the 1,2,4,5,7-pentoxocanes 18, 19 were prepared by the reaction of an alpha,alpha'-bis(trimethylsilylperoxy) ether 17 and carbonyl compounds. The tetroxane 14 showed notable antimalarial activity in vitro and in vivo.