title: Synthesis and antimalarial activities of optically active labdane-type diterpenes.
abstract: An efficient method for the synthesis of optically active labdane-type diterpenes from (+)-manool 8 is described. We prepared the natural labdane-type diterpene 5 via key intermediate peroxide 9, and synthetic hydroxybutenolides 6 and 7 via a furan photosensitised oxygenation reaction of labdafuran (14). Compounds 5, 6, 7 and 9 were evaluated as inhibitors of the beta-haematin formation and globin proteolysis, and then were assayed in a malarial murine model. Compound 9 was the most promising compound, showing a positive correlation between in vitro and in vivo activities.
authors.affiliation: Centro de Química, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas 1020-A, Venezuela. jvillami@ivic.ve
authors.forename: José
authors.initials: J
authors.lastname: Villamizar
authors.forename: Jean P
authors.initials: JP
authors.lastname: Pittelaud
authors.forename: Juan R
authors.initials: JR
authors.lastname: Rodrigues
authors.forename: Neira
authors.initials: N
authors.lastname: Gamboa
authors.forename: Nieves
authors.initials: N
authors.lastname: Canudas
authors.forename: Eleonora
authors.initials: E
authors.lastname: Tropper
authors.forename: Franklin
authors.initials: F
authors.lastname: Salazar
authors.forename: Juan
authors.initials: J
authors.lastname: Fuentes
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004224:Diterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D051379:Mice; D015394:Molecular Structure; D010962:Plasmodium berghei / Q000187:drug effects*; D030521:Zingiberaceae / Q000737:chemistry
chemical_list: D000962:Antimalarials; D004224:Diterpenes; C482828:manool