title: The first synthesis of substituted azepanes mimicking monosaccharides: a new class of potent glycosidase inhibitors.
abstract: The synthesis of the first examples of seven-membered ring iminoalditols, molecules displaying an extra hydroxymethyl substituent on their seven-membered ring compared to the previously reported polyhydroxylated azepanes, has been achieved from d-arabinose in 10 steps using RCM of a protected N-allyl-aminohexenitol as a key step. While the (2R,3R,4R)-2-hydroxymethyl-3,4-dihydroxy-azepane 10, a seven-membered ring analogue of fagomine, is a weak inhibitor of glycosidases, the (2R,3R,4R,5S,6S)-2-hydroxymethyl-3,4,5,6-tetrahydroxy-azepane 9 selectively inhibits green coffee bean alpha-galactosidase in the low micromolar range (Ki = 2.2 muM) despite a D-gluco relative configuration.
authors.affiliation: Ecole Normale Supérieure, Département de Chimie, UMR 8642, 24 rue Lhomond, 75231 Paris 05, France.
authors.forename: Hongqing
authors.initials: H
authors.lastname: Li
authors.forename: Yves
authors.initials: Y
authors.lastname: Blériot
authors.forename: Caroline
authors.initials: C
authors.lastname: Chantereau
authors.forename: Jean-Maurice
authors.initials: JM
authors.lastname: Mallet
authors.forename: Matthieu
authors.initials: M
authors.lastname: Sollogoub
authors.forename: Yongmin
authors.initials: Y
authors.lastname: Zhang
authors.forename: Eliazar
authors.initials: E
authors.lastname: Rodríguez-García
authors.forename: Pierre
authors.initials: P
authors.lastname: Vogel
authors.forename: Jesús
authors.initials: J
authors.lastname: Jiménez-Barbero
authors.forename: Pierre
authors.initials: P
authors.lastname: Sinaÿ
mesh_terms: D001089:Arabinose / Q000737:chemistry; D044602:Cellulases / Q000037:antagonists & inhibitors / Q000378:metabolism; D018360:Crystallography, X-Ray; D003500:Cyclization; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D065089:Glycoside Hydrolase Inhibitors; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006573:Heterocyclic Compounds, 1-Ring / Q000737:chemistry; D007097:Imines / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D015394:Molecular Structure; D009005:Monosaccharides / Q000737:chemistry; D013402:Sugar Alcohols / Q000737:chemistry; D000519:alpha-Galactosidase / Q000037:antagonists & inhibitors / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism; D001616:beta-Galactosidase / Q000037:antagonists & inhibitors / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D065089:Glycoside Hydrolase Inhibitors; D006573:Heterocyclic Compounds, 1-Ring; D007097:Imines; D009005:Monosaccharides; D013402:Sugar Alcohols; D001089:Arabinose; D044602:Cellulases; D006026:Glycoside Hydrolases; D000520:alpha-Glucosidases; D000519:alpha-Galactosidase; D001616:beta-Galactosidase