title: Synthesis of a C-glucosylated cyclopropylamide and evaluation as a glycogen phosphorylase inhibitor.
abstract: The synthesis of carbohydrate-based glycogen phosphorylase inhibitors is attractive for potential applications in the treatment of type 2 diabetes. A titanium-mediated synthesis led to a benzoylated C-glucosylated cyclopropylamine intermediate, which underwent a benzoyl migration to afford the corresponding 2-hydroxy-C-glycoside. X-ray crystallographic studies revealed a unit cell composed of four molecules as pairs of dimers connected through two hydrogen bonds. The deprotection of the benzoate esters under Zemplén conditions afforded a glycogen phosphorylase inhibitor candidate displaying weak inhibition toward glycogen phosphorylase (16% at 2.5mM).
authors.affiliation: CNRS UMR 6011, Unité de Chimie Organique Moléculaire et Macromoléculaire (UCO2M), Université du Maine, Avenue O. Messiaen, F-72085 Le Mans Cedex 9, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Bertus
authors.forename: Jan
authors.initials: J
authors.lastname: Szymoniak
authors.forename: Erwann
authors.initials: E
authors.lastname: Jeanneau
authors.forename: Tibor
authors.initials: T
authors.lastname: Docsa
authors.forename: Pál
authors.initials: P
authors.lastname: Gergely
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Praly
authors.forename: Sébastien
authors.initials: S
authors.lastname: Vidal
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D019281:Dimerization; D004353:Drug Evaluation, Preclinical; D005960:Glucosides / Q000138:chemical synthesis / Q000494:pharmacology; D006003:Glycogen / Q000378:metabolism*; D025001:Glycogen Phosphorylase, Liver Form / Q000037:antagonists & inhibitors / Q000378:metabolism; D024982:Glycogen Phosphorylase, Muscle Form / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006031:Glycosylation; D011817:Rabbits
chemical_list: D001549:Benzamides; D005960:Glucosides; D006003:Glycogen; D025001:Glycogen Phosphorylase, Liver Form; D024982:Glycogen Phosphorylase, Muscle Form