title: The Staudinger/aza-Wittig/Grignard reaction as key step for the concise synthesis of 1-C-Alkyl-iminoalditol glycomimetics.
abstract: The scope of a one-pot tandem approach for the synthesis of C-1 alkyl iminoalditol derivatives with a Staudinger/aza-Wittig/Grignard cascade has been evaluated. The reaction conditions have been optimized for two azidodeoxy aldose substrates and a range of Grignard reagents. The nature of both, substrate as well as nucleophile, was found to control the stereoselectivity of the alkyl addition to the cyclic iminium intermediate at position C-1. This approach enabled the synthesis of a collection of C-alkyl iminoalditols, which were biologically evaluated as inhibitors against a set of standard glycoside hydrolases. All compounds were found to exhibit highly selective inhibition of β-glucosidase activity.
authors.affiliation: Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Manuel
authors.initials: M
authors.lastname: Zoidl
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Andres
authors.initials: A
authors.lastname: Gonzalez Santana
authors.affiliation: Institute of Inorganic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria.
authors.forename: Ana
authors.initials: A
authors.lastname: Torvisco
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Christina
authors.initials: C
authors.lastname: Tysoe
authors.affiliation: Laboratoire des Glycochimie, des Antimicrobiens et des Agroressources (UMR 7378 CNRS), Université de Picardie Jules Verne, 33 Rue St Leu, 80039 Amiens, France.
authors.forename: Aloysius
authors.initials: A
authors.lastname: Siriwardena
authors.affiliation: Department of Chemistry, University of British Columbia, 2036 Main Mall, Vancouver, BC, Canada V6T 1Z1.
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Withers
authors.affiliation: Glycogroup, Institute of Organic Chemistry, Graz University of Technology, Stremayrgasse 9, A-8010 Graz, Austria. Electronic address: t.wrodnigg@tugraz.at.
authors.forename: Tanja M
authors.initials: TM
authors.lastname: Wrodnigg
mesh_terms: D000473:Alkanes / Q000737:chemistry; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006026:Glycoside Hydrolases / Q000037:antagonists & inhibitors* / Q000737:chemistry; D018716:Molecular Mimicry; D011134:Polysaccharides / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013402:Sugar Alcohols / Q000138:chemical synthesis* / Q000737:chemistry; D001617:beta-Glucosidase / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D000473:Alkanes; D004791:Enzyme Inhibitors; D011134:Polysaccharides; D013402:Sugar Alcohols; D006026:Glycoside Hydrolases; D001617:beta-Glucosidase
keywords: C-glycoside iminosugars; Glycomimetics; Staudinger/aza Wittig/Grignard reaction cascade; β-glucosidase inhibitors