Physical Sciences and Mathematics Commons^™

Synthesis And Antimalarial Activity Of 11 Dispiro-1,2,4,5-Tetraoxane Analogues Of Wr 148999. 7,8,15,16-Tetraoxadispiro[5.2.5.2]Hexadecanes Substituted At The 1 And 10 Positions With Unsaturated And Polar Functional Groups, Yuxiang Dong, F. Hoffmann-Laroche Ltd., Jacques Chollet, Ronald Kaminsky, James K. Wood, Jonathan L. Vennerstrom

Chemistry Faculty Publications

Eleven novel dispiro-1,2,4,5-tetraoxanes 3 bearing unsaturated and polar functional groups were designed to enhance the oral antimalarial activity of the prototype tetraoxane 2 (WR 148999). With the exception of 3g and 3h, tetraoxanes 3 were available via the peroxidation of corresponding cyclohexanone derivatives in H2SO4/CH3CN. Tetraoxanes 3g and 3h were prepared by hydrolysis of ester tetraoxanes 3e and 3i, respectively. Five of the 11 tetraoxanes were inactive, but six tetraoxanes had IC₅₀ values of 6-26 nM against the K1 and NF54 strains of Plasmodium falciparum compared to corresponding IC₅₀ values of 28 and 39 nM for …