Synthesis and anti-malarial activity of yingzhaosu A analogues from unsaturated hydroperoxy acetals

Ozonolysis of a vinyl ether 2, prepared from dihydrocarvone 1 (a 1:4 mixture of cis- and trans-isomer), in methanol gave two isomeric unsaturated hydroperoxy acetals cis- and trans-3. Iodonium ion- or ozone-mediated cyclizations of the hydroperoxide cis-3 gave the corresponding yingzhaosu A analogues 4 and 6 in moderate yields. The peroxide 8, obtained by the Ag2O-mediated methylation of 6, showed notable anti-malarial activity in vitro (IC50=1.0×10−7 M).