title: Synthesis and biological evaluation of (-)-6-O-desmethylcryptopleurine and analogs.
abstract: (-)-Cryptopleurine 1 is one of the most potent anti-proliferative member of the phenanthroquinolizidine class of alkaloids. We report here the synthesis of (-)-6-O-desmethylcryptopleurine (-)-2 and (-)-6-O-desmethyl-(15R)-hydroxycryptopleurine (-)-4 in their enantiomerically enriched form through a convergent synthetic route, where the chirality is introduced by the use of commercially available (R)-methyl piperidine-2-carboxylate hydrochloride 17. Anti-proliferative activities of these compounds were evaluated on a panel of four cancer cell lines, revealing that compounds (-)-2 and (-)-4 are potent cytotoxic compared to cryptopleurine.
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France. Electronic address: frederic.lieby.muller@pierre-fabre.com.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Liéby-Muller
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Marion
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Schmitt
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Jean-Philippe
authors.initials: JP
authors.lastname: Annereau
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Anna
authors.initials: A
authors.lastname: Kruczynski
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Guilbaud
authors.affiliation: Institut de Recherche Pierre Fabre, CRDPF/CROE, 3 avenue Hubert Curien, BP 13562, 31035 Toulouse Cedex 1, France.
authors.forename: Christian
authors.initials: C
authors.lastname: Bailly
mesh_terms: D000470:Alkaloids / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects / Q000502:physiology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006801:Humans
chemical_list: D000470:Alkaloids; C007160:cryptopleurine
keywords: (−)-Cryptopleurine; Cytotoxicity; Phenanthroquinolizidine alkaloid