title: N-O bond as a glycosidic-bond surrogate: synthetic studies toward polyhydroxylated N-alkoxypiperidines.
abstract: A series of novel polyhydroxylated N-alkoxypiperidines has been synthesized by ring-closing double reductive amination (DRA) of highly functionalized 1,5-dialdehydes with various hydroxylamines. The required saccharide-based dialdehydes were prepared efficiently from sodium cyclopentadienylide in seven steps. A two-step protocol has been developed for the DRA; it led, after deprotection, to isofagomine, 3-deoxyisofagomine, and numerous other N-alkoxy analogues. The barrier to inversion in these polyhydroxylated N-alkoxypiperidine derivatives was found by variable-temperature NMR methods to be approximately 15 kcal mol(-1). With the exception of N-hydroxyisofagomine itself, none of the compounds prepared showed significant inhibitory activity against sweet almond β-glucosidase.
authors.affiliation: Centre de Recherche de Gif, Institut de Chimie des Substances Naturelles, CNRS, Avenue de la Terrasse, 91198 Gif-sur-Yvette, France.
authors.forename: Gaëlle
authors.initials: G
authors.lastname: Malik
authors.forename: Angélique
authors.initials: A
authors.lastname: Ferry
authors.forename: Xavier
authors.initials: X
authors.lastname: Guinchard
authors.forename: Thierry
authors.initials: T
authors.lastname: Cresteil
authors.forename: David
authors.initials: D
authors.lastname: Crich
mesh_terms: D000586:Amination; D050112:Imino Pyranoses / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010880:Piperidines / Q000737:chemistry*; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry*
chemical_list: D050112:Imino Pyranoses; D010880:Piperidines; C098432:isofagomine; D001617:beta-Glucosidase