SYNTHESIS AND ANTIMALARIAL ACTIVITIES OF STRUCTURALLY SIMPLIFIED 1,2,4-TRIOXANES RELATED TO ARTEMISININ

Eleven derivatives of the clinically useful, antimalarial, 1,2,4-triox ane artemisinin have been synthesized in only several steps from comme rcial cyclohexanones. Of these simple, tricyclic 1,2,4-trioxanes, 10 s howed considerable in vitro antimalarial activity, with one being as p otent as artemisinin. Some structure-activity relationship generalizat ions are made from this series of artemisinin analogs. Triethylsilyl h ydrotrioxide (Et(3)SiOOOH), prepared in situ from ozone and triethylsi lane, is shown to be a mild, fast-acting, and effective dioxetane-form ing reagent with vinyl ethers and with a vinyl thioether on relatively small (50-100 mg) scale.