title: Asymmetric synthesis and biological evaluation of natural or bioinspired cytotoxic C2-symmetrical lipids with two terminal chiral alkynylcarbinol pharmacophores.
abstract: Bidirectional syntheses of C2-symmetrical lipids embedding two terminal alkynylcarbinol pharmacophores are reported. Naturally occurring chiral alkenylalkynylcarbinol units were generated using Pu's procedure for enantioselective addition of terminal alkynes to aldehydes, allowing the first asymmetric synthesis of (3R,4E,16E,18R)-icosa-4,16-diene-1,19-diyne-3,18-diol, isolated from Callyspongia pseudoreticulata. Two synthetic analogues embedding the recently uncovered (S)-dialkynylcarbinol pharmacophore were secured using Carreira's procedure adapted to ynal substrates. The dramatic effect of the carbinol configuration on cytotoxicity was confirmed with submicromolar IC50 values against HCT116 cells.
authors.affiliation: †UPR CNRS 8241, LCC, Université de Toulouse, 205 route de Narbonne, F-31077 Toulouse, France.|‡Université de Toulouse, Université Paul Sabatier, INPT, F-31077 Toulouse, France.|§Kiev National Taras Shevchenko University, 60 Volodymyrska Street, 01033 Kiev, Ukraine.|∥UMR CNRS 5068, LSPCMIB, Université Paul Sabatier, 118 route de Narbonne, Toulouse, 31062 Cedex 9, France.
authors.forename: Dymytrii
authors.initials: D
authors.lastname: Listunov
authors.affiliation: ∥UMR CNRS 5068, LSPCMIB, Université Paul Sabatier, 118 route de Narbonne, Toulouse, 31062 Cedex 9, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Fabing
authors.affiliation: ⊥Institut de Chimie de Toulouse, ICT FR 2599, Université Paul Sabatier - Toulouse III, Toulouse 31062 Cedex 9, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Saffon-Merceron
authors.affiliation: ∥UMR CNRS 5068, LSPCMIB, Université Paul Sabatier, 118 route de Narbonne, Toulouse, 31062 Cedex 9, France.
authors.forename: Hafida
authors.initials: H
authors.lastname: Gaspard
authors.affiliation: §Kiev National Taras Shevchenko University, 60 Volodymyrska Street, 01033 Kiev, Ukraine.
authors.forename: Yulian
authors.initials: Y
authors.lastname: Volovenko
authors.affiliation: †UPR CNRS 8241, LCC, Université de Toulouse, 205 route de Narbonne, F-31077 Toulouse, France.|‡Université de Toulouse, Université Paul Sabatier, INPT, F-31077 Toulouse, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Maraval
authors.affiliation: †UPR CNRS 8241, LCC, Université de Toulouse, 205 route de Narbonne, F-31077 Toulouse, France.|‡Université de Toulouse, Université Paul Sabatier, INPT, F-31077 Toulouse, France.
authors.forename: Remi
authors.initials: R
authors.lastname: Chauvin
authors.affiliation: ∥UMR CNRS 5068, LSPCMIB, Université Paul Sabatier, 118 route de Narbonne, Toulouse, 31062 Cedex 9, France.
authors.forename: Yves
authors.initials: Y
authors.lastname: Génisson
mesh_terms: D000480:Alkynes / Q000737:chemistry*; D001686:Biological Phenomena; D002384:Catalysis; D053280:Diynes / Q000138:chemical synthesis* / Q000737:chemistry; D045325:HCT116 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008055:Lipids / Q000138:chemical synthesis* / Q000737:chemistry; D000432:Methanol / Q000737:chemistry*; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: C584221:(4E,16E)-icosa-4,16-diene-1,19-diyne-3,18-diol; D000480:Alkynes; D053280:Diynes; D008055:Lipids; D000432:Methanol