title: Conception, synthesis, and biological evaluation of original discodermolide analogues.
abstract: Due to its intriguing biological activity profile and potential chemotherapeutic application discodermolide (DDM) proved to be an attractive target. Therefore, notable efforts have been carried out directed toward its total synthesis and toward the production and evaluation of synthetic analogues. Recently, we achieved the total synthesis of DDM. At the present, guided by the knowledge gained during our DDM total synthesis and by the requirement of keeping the bioactive "U" shape conformation, we report the convergent preparation of five original analogues. Three types of changes were realized through modification of the terminal (Z)-diene moiety, of the methyl group at the C14-position, and the lactone region. All analogues were active in the nanomolar range and two of them turned out to be equipotent to DDM.
authors.affiliation: Université Paris Descartes, Faculté de Pharmacie, CNRS UMR 8638, 4 avenue de l'Observatoire, 75270 Paris Cedex, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: de Lemos
authors.forename: Evangelos
authors.initials: E
authors.lastname: Agouridas
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Sorin
authors.forename: Antonio
authors.initials: A
authors.lastname: Guerreiro
authors.forename: Alain
authors.initials: A
authors.lastname: Commerçon
authors.forename: Ange
authors.initials: A
authors.lastname: Pancrazi
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Betzer
authors.forename: Marie-Isabelle
authors.initials: MI
authors.lastname: Lannou
authors.forename: Janick
authors.initials: J
authors.lastname: Ardisson
mesh_terms: D000473:Alkanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002219:Carbamates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011753:Pyrones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000473:Alkanes; D002219:Carbamates; D007783:Lactones; D011753:Pyrones; C071229:discodermolide