title: Synthesis and anti-inflammatory activity of isoquebecol.
abstract: We report here the synthesis of isoquebecol, an unprecedented constitutional isomer of quebecol, a polyphenolic compound discovered in maple syrup. The methodology used to prepare isoquebecol involves, as key steps, the formation of a dibromoalkene from an α-ketoester precursor, followed by a double Suzuki-Miyaura reaction. The anti-inflammatory activity of isoquebecol was studied on macrophage cells by monitoring its ability to inhibit LPS-induced IL-6 secretion. Results show that this new compound has an improved bioactivity over that of its natural isomer. Precursors and derivatives of quebecol, isoquebecol and model analog 2,3,3-triphenylpropanol were also prepared and tested in this study. Comparison between the three series of compounds led to establishing new SARs concerning the aryl ring substitution pattern on the triarylpropanol scaffold and substructure functionalization.
authors.affiliation: Département de Chimie and PROTEO, Université Laval, 1045 Avenue de la Médecine, Québec G1V 0A6, Canada.
authors.forename: Sébastien
authors.initials: S
authors.lastname: Cardinal
authors.affiliation: Département de Chimie and PROTEO, Université Laval, 1045 Avenue de la Médecine, Québec G1V 0A6, Canada.
authors.forename: Pierre-Alexandre
authors.initials: PA
authors.lastname: Paquet-Côté
authors.affiliation: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de la Terrasse, Québec G1V 0A6, Canada.
authors.forename: Jabrane
authors.initials: J
authors.lastname: Azelmat
authors.affiliation: Département de Chimie and PROTEO, Université Laval, 1045 Avenue de la Médecine, Québec G1V 0A6, Canada.
authors.forename: Corinne
authors.initials: C
authors.lastname: Bouchard
authors.affiliation: Groupe de Recherche en Écologie Buccale, Faculté de Médecine Dentaire, Université Laval, 2420 Rue de la Terrasse, Québec G1V 0A6, Canada.
authors.forename: Daniel
authors.initials: D
authors.lastname: Grenier
authors.affiliation: Département de Chimie and PROTEO, Université Laval, 1045 Avenue de la Médecine, Québec G1V 0A6, Canada. Electronic address: normand.voyer@chm.ulaval.ca.
authors.forename: Normand
authors.initials: N
authors.lastname: Voyer
mesh_terms: D000893:Anti-Inflammatory Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006139:Guaiacol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D013267:Stilbenes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D020298:U937 Cells
chemical_list: D000893:Anti-Inflammatory Agents; D015850:Interleukin-6; D008070:Lipopolysaccharides; D013267:Stilbenes; C000622716:isoquebecol; D006139:Guaiacol
keywords: Anti-inflammatory activity; Inhibition of IL-6 secretion; Isoquebecol; Quebecol; SAR studies