Antimalarial Cyclic Peroxy Ketals

Over 20 new, cyclic, peroxy ketals have been prepared via a two-step protocol starting with readily available aryl methyl ketones. Structure−activity correlations using in vitro antimalarial data as a guide for optimization of potency have led to the design and synthesis of seven new peroxides that have IC₅₀ values of 31−85 nM (artemisinin IC₅₀ = 8.4 nM). Some SAR generalizations are discussed.