title: An isofagomine analogue with an amidine at the pseudoanomeric position.
abstract: (3R,4R,5R)-2-Imino-3,4-dihydroxy-5-hydroxymethylpiperidine hydrocloride or isofagomidine was synthesized from D-arabinose in 12 steps and an overall yield of 9.9%. The synthesis proceeded by introduction of an aminomethyl group in the 4-position of D-arabinose and conversion of C-1 into a nitrile. The key step in the synthesis was a copper-catalyzed cyclization of aminonitrile to amidine. Isofagomidine was a potent α-mannosidase inhibitor (K(i) = 0.75 μM).
authors.affiliation: Department of Chemistry, University of Copenhagen, Copenhagen, Denmark.
authors.forename: Emil
authors.initials: E
authors.lastname: Lindbäck
authors.forename: Oscar
authors.initials: O
authors.lastname: López
authors.forename: José G
authors.initials: JG
authors.lastname: Fernández-Bolaños
authors.forename: Stephan P A
authors.initials: SP
authors.lastname: Sauer
authors.forename: Mikael
authors.initials: M
authors.lastname: Bols
mesh_terms: D000578:Amidines / Q000737:chemistry*; D001089:Arabinose / Q000737:chemistry*; D050112:Imino Pyranoses / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D043323:alpha-Mannosidase / Q000037:antagonists & inhibitors*
chemical_list: D000578:Amidines; D050112:Imino Pyranoses; C098432:isofagomine; D001089:Arabinose; D043323:alpha-Mannosidase