title: Iron(II)-induced degradation of antimalarial beta-sulfonyl endoperoxides: evidence for the generation of potentially cytotoxic carbocations.
abstract: Reactions of antimalarial beta-sulfonyl endoperoxides 9 and 10, which, like yingzhaosu A (2), derive from the 2,3-dioxabicyclo[3.3.1]nonane system 3, with iron(II) salts were studied. Product analysis of the iron(II)-induced degradations provided evidence for the intermediacy of carbon-centered cyclohexyl radicals 20 and 31 and their possible oxidation to the corresponding carbocations 21 and 32. It is conceivable that the antimalarial activity of beta-sulfonyl endoperoxides of type 5 may derive from alkylation of vital intraparasitic biomolecules by free radicals and/or carbocations, generated within the malaria parasite through a similar iron(II)-induced degradation process.
authors.affiliation: Department of Organic Chemistry, The Weizmann Institute of Science, 76100 Rehovot, Israel.
authors.forename: A M
authors.initials: AM
authors.lastname: Szpilman
authors.forename: E E
authors.initials: EE
authors.lastname: Korshin
authors.forename: R
authors.initials: R
authors.lastname: Hoos
authors.forename: G H
authors.initials: GH
authors.lastname: Posner
authors.forename: M D
authors.initials: MD
authors.lastname: Bachi
mesh_terms: D000962:Antimalarials / Q000737:chemistry / Q000378:metabolism*; D005609:Free Radicals / Q000737:chemistry / Q000378:metabolism; D007501:Iron / Q000494:pharmacology*; D010084:Oxidation-Reduction; D010545:Peroxides / Q000737:chemistry / Q000378:metabolism* / Q000627:therapeutic use; D011355:Prodrugs / Q000737:chemistry / Q000378:metabolism; D013441:Sulfinic Acids / Q000737:chemistry
chemical_list: D000962:Antimalarials; D005609:Free Radicals; D010545:Peroxides; D011355:Prodrugs; D013441:Sulfinic Acids; D007501:Iron