title: Synthesis of 2-carboxymethyl polyhydroxyazepanes and their evaluation as glycosidase inhibitors.
abstract: A series of diastereomeric tetrahydroxylated azepanes featuring a carboxymethyl group at the pseudo-anomeric position have been synthesized from a common unsaturated intermediate. Syn- and anti-dihydroxylation reactions were achieved to yield the target compounds after efficient one-step deprotection of carbamate, ester and acetonide groups simultaneously. Screening of these polyhydroxylated azepanes toward a range of commercially available glycosidases was performed and one of the stereoisomers showed potent and selective inhibition toward β-galactosidase (IC50=21 μM).
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France.
authors.forename: Hanaa
authors.initials: H
authors.lastname: Taghzouti
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Goumain
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France.
authors.forename: Dominique
authors.initials: D
authors.lastname: Harakat
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France.
authors.forename: Charles
authors.initials: C
authors.lastname: Portella
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France. Electronic address: jb.behr@univ-reims.fr.
authors.forename: Jean-Bernard
authors.initials: JB
authors.lastname: Behr
authors.affiliation: Université de Reims Champagne-Ardenne, Institut de Chimie Moléculaire de Reims (ICMR), CNRS UMR 7312, UFR Sciences Exactes et Naturelles, BP 1039, F-51687 Reims Cedex 2, France. Electronic address: richard.plantier-royon@univ-reims.fr.
authors.forename: Richard
authors.initials: R
authors.lastname: Plantier-Royon
mesh_terms: D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D066241:Carbon-13 Magnetic Resonance Spectroscopy; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors*; D008958:Models, Molecular; D066244:Proton Magnetic Resonance Spectroscopy; D021241:Spectrometry, Mass, Electrospray Ionization; D013237:Stereoisomerism
chemical_list: D001381:Azepines; D004791:Enzyme Inhibitors; D006026:Glycoside Hydrolases
keywords: Azepane; Dihydroxylation; Glycosidase; Iminosugar; Inhibition