Spiro- and dispiro-1,2-dioxolanes: contribution of iron(II)-mediated one-electron vs two-electron reduction to the activity of antimalarial peroxides.
J Med Chem
; 50(23): 5840-7, 2007 Nov 15.
Article
en En
| MEDLINE
| ID: mdl-17949067
ABSTRACT
Fourteen spiro- and dispiro-1,2-dioxolanes were synthesized by peroxycarbenium ion annulations with alkenes in yields ranging from 30% to 94%. Peroxycarbenium ion precursors included triethylsilyldiperoxyketals and -acetals derived from geminal dihydroperoxides and from a new method employing triethylsilylperoxyketals and -acetals derived from ozonolysis of alkenes. The 1,2-dioxolanes were either inactive or orders of magnitude less potent than the corresponding 1,2,4-trioxolanes or artemisinin against P. falciparum in vitro and P. berghei in vivo. In reactions with iron(II), the predominant reaction course for 1,2-dioxolane 3a was two-electron reduction. In contrast, the corresponding 1,2,4-trioxolane 1 and the 1,2,4-trioxane artemisinin undergo primarily one-electron iron(II)-mediated reductions. The key structural element in the latter peroxides appears to be an oxygen atom attached to one or both of the peroxide-bearing carbon atoms that permits rapid beta-scission reactions (or H shifts) to form primary or secondary carbon-centered radicals rather than further reduction of the initially formed Fe(III) complexed oxy radicals.
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Banco de datos:
MEDLINE
Asunto principal:
Peróxidos
/
Compuestos de Espiro
/
Compuestos Ferrosos
/
Dioxolanos
/
Antimaláricos
Límite:
Animals
Idioma:
En
Año:
2007
Tipo del documento:
Article