title: Relative stereochemical determination and synthesis of the C17-C25 δ-lactone fragment of hemicalide.
abstract: Hemicalide is a novel marine metabolite polyketide distinguished by a unique mechanism of action. Because of insufficient quantities of purified material, this natural product has evaded complete stereochemical assignments. Recently, we have determined the relative stereochemistry of the C8-C13 hexad by synthesizing the C1-C13 fragment. Presently, we report the assignment of the C17-C25 δ-lactone fragment. NMR analysis of authentic hemicalide along with a computational conformation study allowed us to reduce the number of putative relative isomers from 16 to 4. Concise syntheses of the four candidate diastereomers were achieved using a common strategy based on a Dias aldehyde allylation reaction, an intramolecular Horner-Wadsworth-Emmons olefination, and a dihydroxylation reaction. Finally, thorough NMR comparisons enabled us to deduce the relative stereochemistry of the C1-C17 fragment with high certainty.
authors.affiliation: CNRS UMR 8638, Faculté de Pharmacie, Université Paris Descartes, 4 avenue de l'observatoire, 75270 Paris Cedex 06, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Fleury
authors.forename: Geoffroy
authors.initials: G
authors.lastname: Sorin
authors.forename: Elise
authors.initials: E
authors.lastname: Prost
authors.forename: Ange
authors.initials: A
authors.lastname: Pancrazi
authors.forename: François
authors.initials: F
authors.lastname: Sautel
authors.forename: Georges
authors.initials: G
authors.lastname: Massiot
authors.forename: Marie-Isabelle
authors.initials: MI
authors.lastname: Lannou
authors.forename: Janick
authors.initials: J
authors.lastname: Ardisson
mesh_terms: D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry; D018942:Macrolides / Q000138:chemical synthesis* / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D061065:Polyketides / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism
chemical_list: D007783:Lactones; D018942:Macrolides; D061065:Polyketides