title: Synthesis of antitrypanosomal 1,2-dioxane derivatives based on a natural product scaffold.
abstract: A short practical synthesis of a new natural product based scaffold (6), based on antitrypanosomal and antimalarial compounds isolated from different Plakortis species is described. The scaffold contains a peroxide unit that is surprisingly stable to chemical manipulation elsewhere in the molecule, enabling it to be elaborated into a small library of derivatives. It is stable to ozonolysis, reductive work-up with dimethylsulfide and the Wittig reaction with stabilized phosphorus ylides. The scaffold along with its Wittig analogues has displayed low to sub-micro molar (0.2-3.3 μM) antitrypanosomal activity.
authors.affiliation: Eskitis Institute, Griffith University, Brisbane QLD4111, Australia.
authors.forename: Harish
authors.initials: H
authors.lastname: Holla
authors.forename: Mehdi
authors.initials: M
authors.lastname: Labaied
authors.forename: Ngoc
authors.initials: N
authors.lastname: Pham
authors.forename: Ian D
authors.initials: ID
authors.lastname: Jenkins
authors.forename: Kenneth
authors.initials: K
authors.lastname: Stuart
authors.forename: Ronald J
authors.initials: RJ
authors.lastname: Quinn
mesh_terms: D000818:Animals; D001685:Biological Factors / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D004146:Dioxanes / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015394:Molecular Structure; D021261:Parasitic Sensitivity Tests; D047229:Plakortis / Q000737:chemistry*; D054852:Small Molecule Libraries; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D014346:Trypanosoma brucei brucei / Q000187:drug effects*
chemical_list: D001685:Biological Factors; D004146:Dioxanes; D054852:Small Molecule Libraries; D014344:Trypanocidal Agents