Diels-Alder/thiol-olefin co-oxygenation approach to antimalarials incorporating the 2,3-dioxabicyclo[3.3.1]nonane pharmacophore

Bioorganic & Medicinal Chemistry Letters
P M O'NeillM D Bachi

Abstract

A Diels-Alder/thiol-olefin co-oxygenation approach to the synthesis of novel bicyclic endoperoxides 17a-22b is reported. Some of these endoperoxides (e.g., 17b, 19b, 22a and 22b) have potent nanomolar in vitro antimalarial activity equivalent to that of the synthetic antimalarial agent arteflene. Iron(II)-mediated degradation of sulfone-endoperoxide 19b and spin-trapping with TEMPO provide a spin-trapped adduct 25 indicative of the formation of a secondary carbon centered radical species 24. Reactive C-radical intermediates of this type may be involved in the expression of the antimalarial effect of these bicyclic endoperoxides.

References

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Aug 22, 2003·Nature·U Eckstein-LudwigS Krishna
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Citations

Dec 23, 2014·Organic & Biomolecular Chemistry·Yu-Chang LiuZhong-Liu Wu
Jan 24, 2014·Beilstein Journal of Organic Chemistry·Alexander O Terent'evValery M Dembitsky
May 11, 2018·Topics in Current Chemistry·Richard S Glass
Apr 30, 2015·The Journal of Organic Chemistry·Shao-Fang ZhouJian-Ping Zou

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