Chang Ho Oh

Enantiomeric 1,2,4-Trioxanes Display Equivalent in vitro Antimalarial Activity Versus Plasmodium falciparum Malaria Parasites: Implications for the Molecular Mechanism of Action of the Artemisinins

The aim of this study was to synthesise pure enantiomers of potent antimalarial 1,2,4‐trioxanes, which are related to the natural antimalarial artemisinin, and then to assay each against a panel of Plasmodium falciparum strains. The working hypothesis was that if the artemisinin derivatives interact with a specific protein‐target site, then there should be stereoselective differences in their activity. In five different P. falciparum isolates, however, the trioxane enantiomers (+)‐7u2009a, (−)‐7u2009a and (+)‐7u2009b, (−)‐7u2009b, showed the same level of in vitro antiparasitic activity.

BF3·OEt2 promotes fast, mild, clean and regioselective dehydration of tertiary alcohols

Abstract BF 3 ·OEt 2 in methylene chloride at 25°C for 2 hours or less is shown to be effective for easy conversion of tertiary alcohols into the corresponding thermodynamically most stable alkenes.

Olefin oxidative cleavage and dioxetane formation using triethylsilyl hydrotrioxide: Applications to preparation of potent antimalarial 1,2,4-trioxanes

Abstract Oxidative cleavage of alkenyl esters and thether using Et 3 SiOOOH was found to be easier than oxidative cleavage of hydrocarbon alkenes, and Et 3 SiOOOH was successfully applied to very short syntheses of new, simple, and potent antimalarial trioxanes 6 and 8 . Triethylsilyl hydrotrioxide was successfully applied to syntheses of new antimalarial 1,2,4-trioxanes 6 8 .

Asymmetric syntheses of enantiomeric 3-p-fluorophenyl 1,2,4-trioxane analogues of the antimalarial artemisinin

Abstract We have devised an asymmetric synthesis of chiral artemisinin analogues (+)- 4a and (−)- 4a that retain the tricyclic ring system found in the natural product. The key step in the preparation of (+)- 4a involves an asymmetric MgCl 2 promoted Michael addition of the ( R )-(−)pyrrolidinemethanol-derived enamine 8 to acrylonitrile. This gives the corresponding ketone 9 in 50% yield (>95% ee). Subsequent elaboration of 9 provides the trioxane target (+)- 4a in greater than 85% ee. Enantiomeric trioxane (−)- 4a was prepared in a similar manner using ( S )-(+)-pyrrolidinemethanol in the first step of the sequence.

Antimalarial 1,2,4-Trioxanes Related to Artemisinin: Rules for Assignment of Relative Stereochemistry in Diversely Substituted Analogs

Abstract A series of rules has been developed, using mainly 1D and 2D NMR spectroscopy, for identification of relative stereochemistry in a variety of substituted antimalarial 1,2,4-trioxanes.