title: Total synthesis and configurational assignment of the marine natural product haliclamide.
abstract: The marine natural product haliclamide has been synthesized based on macrocyclization by ring-closing olefin metathesis. Using either enantiomer of two of the four building blocks that were employed to assemble the diene precursor for the metathesis reaction, three non-natural isomers of haliclamide were also prepared. On the basis of the comparison of the (1)H and (13)C NMR spectra of the individual stereoisomers with literature data for the natural product, the configuration of the previously unassigned stereocenters at C9 and C20 of haliclamide could be determined to be S for both carbons. The absolute configuration of haliclamide thus is 2S, 9S, 14R, 20S. The antiproliferative activity of synthetic haliclamide against several human cancer cell lines was found to be in the high μM range. The compound showed no antifungal or antibiotic activity.
authors: Department of Chemistry and Applied Biosciences, Institute of Pharmaceutical Sciences, ETH Zürich, HCI H405, Wolfgang-Pauli Str. 10, CH-8093 Zürich, Switzerland.
authors: Bernhard
authors: B
authors: Pfeiffer
authors: Sandra
authors: S
authors: Speck-Gisler
authors: Luzi
authors: L
authors: Barandun
authors: Ursula
authors: U
authors: Senft
authors: Claire
authors: C
authors: de Groot
authors: Irène
authors: I
authors: Lehmann
authors: Walter
authors: W
authors: Ganci
authors: Jürg
authors: J
authors: Gertsch
authors: Karl-Heinz
authors: KH
authors: Altmann
mesh_terms: D000475:Alkenes / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry; D045744:Cell Line, Tumor; D047630:Depsipeptides / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D018942:Macrolides / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D013237:Stereoisomerism
chemical_list: D000475:Alkenes; D000970:Antineoplastic Agents; D001688:Biological Products; D047630:Depsipeptides; D018942:Macrolides; C584065:haliclamide