221293-75-0Relevant articles and documents
A short synthesis and biological evaluation of potent and nontoxic antimalarial bridged bicyclic β-sulfonyl-endoperoxides
Bachi, Mario D.,Korshin, Edward E.,Hoos, Roland,Szpilman, Alex M.,Ploypradith, Poonsakdi,Xie, Suji,Shapiro, Theresa A.,Posner, Gary H.
, p. 2516 - 2533 (2003)
The syntheses and in vitro antimalarial screening of 50 bridged, bicyclic endoperoxides of types 9-13 are reported. In contrast to antimalarial trioxanes of the artemisinin family, but like yingzhaosu A and arteflene, the peroxide function of compounds 9-13 is contained in a 2,3-dioxabicyclo[3.3.1]nonane system 6. Peroxides 9 and 10 (R1 = OH) are readily available through a multicomponent, sequential, free-radical reaction involving thiol-monoterpenes co-oxygenation (a TOCO reaction). β-Sulfenyl peroxides 9 and 10 (R1 = OH) are converted into β-sulfinyl and β-sulfonyl peroxides of types 11-13 by controlled S-oxidation and manipulation of the terthydroxyl group through acylation, alkylation, or dehydration followed by selective hydrogenation. Ten enantiopure β-sulfonyl peroxides of types 12 and 13 exhibit in vitro antimalarial activity comparable to that of artemisinin (IC50 = 6-24 nM against Plasmodium falciparum NF54). In vivo testing of a few selected peroxides against Plasmodium berghei N indicates that the antimalarial efficacies of β-sulfonyl peroxides 39a, 46a, 46b, and 50a are comparable to those of some of the best antimalarial drugs and are higher than artemisinin against chloroquine-resistant Plasmodium yoelii ssp. NS. In view of the nontoxicity of β-sulfonyl peroxides 39a, 46a, and 46b in mice, at high dosing, these compounds are regarded as promising antimalarial drug candidates.
Synthesis and in vitro antimalarial activity of sulfone endoperoxides
Bachi, Mario D.,Korshin, Edward E.,Ploypradith, Poonsakdi,Cumming, Jared N.,Xie, Suji,Shapiro, Theresa A.,Posner, Gary H.
, p. 903 - 908 (2007/10/03)
A series of 4,8-dimethyl-4-phenylsulfonylmethyl-2,3- dioxabicyclo[3.3.l]nonanes, carrying a variety of substituents at position-8 (4) were prepared by a short and efficient method from R-(+)-limonene. Key reactions include thiol oxygen cooxidation, and al
