Synthesis and antimalarial activities of optically active labdane-type diterpenes.
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.
Villamizar
José
J
Centro de Química, Instituto Venezolano de Investigaciones Cientificas (IVIC), Caracas 1020-A, Venezuela. jvillami@ivic.ve
Pittelaud
Jean P
JP
Rodrigues
Juan R
JR
Gamboa
Neira
N
Canudas
Nieves
N
Tropper
Eleonora
E
Salazar
Franklin
F
Fuentes
Juan
J
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
D000962:Antimalarials; D004224:Diterpenes; C482828:manool