title: Stereoselective α-glycosylation of C(6)-hydroxyl myo-inositols via nickel catalysis-application to the synthesis of GPI anchor pseudo-oligosaccharides.
abstract: Glycosylphosphatidyl inositol (GPI) anchors play a key role in many eukaryotic biological pathways. Stereoselective synthesis of GPI anchor analogues have proven to be critical for probing the biosynthesis, structure, and biological properties of these compounds. Challenges that have emerged from these efforts include the preparation of the selectively protected myo-inositol building blocks and the stereoselective construction of glucosamine α-linked myo-inositol containing pseudodisaccharide units. Herein, we describe the effectiveness of the cationic nickel(II) catalyst, Ni(4-F-PhCN)4(OTf)2, at promoting selective formation of 1,2-cis-2-amino glycosidic bonds between the C(2)-N-substituted benzylideneamino trihaloacetimidate donors and C(6)-hydroxyl myo-inositol acceptors. This catalytic coupling process allows rapid access to pseudosaccharides of GPI anchors in good yields and with excellent levels of α-selectivity (α:β=10:1-20:1). In stark contrast, activation of trichloroacetimidate donors containing the C(2)-N-substituted benzylidene group with TMSOTf and BF3(.)OEt2 provided the desired pseudodisaccharides as a 1:1 mixture of α- and β-isomers.
authors.affiliation: Department of Chemistry, University of Iowa, Iowa City, IA 52242, United States.
authors.forename: Matthew S
authors.initials: MS
authors.lastname: McConnell
authors.forename: Enoch A
authors.initials: EA
authors.lastname: Mensah
authors.forename: Hien M
authors.initials: HM
authors.lastname: Nguyen
mesh_terms: D002384:Catalysis; D006031:Glycosylation; D017261:Glycosylphosphatidylinositols / Q000138:chemical synthesis* / Q000737:chemistry; D007294:Inositol / Q000031:analogs & derivatives / Q000737:chemistry*; D008968:Molecular Conformation; D009532:Nickel / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D009942:Organometallic Compounds / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D017261:Glycosylphosphatidylinositols; D009844:Oligosaccharides; D009942:Organometallic Compounds; D007294:Inositol; D009532:Nickel
keywords: 1,2-cis-2-Amino glycosidic bonds; Inositols; N-Substituted benzylidene groups; Nickel catalysis; Pseudosaccharides