Utilization of bench-stable and readily available nickel(II) triflate for access to 1,2-cis-2-aminoglycosides.
The utilization of substoichiometric amounts of commercially available nickel(II) triflate as an activator in the reagent-controlled glycosylation reaction for the stereoselective construction of biologically relevant targets containing 1,2-cis-2-amino glycosidic linkages is reported. This straightforward and accessible methodology is mild, operationally simple and safe through catalytic activation by readily available Ni(OTf)2in comparison to systems employing our previously in-house prepared Ni(4-F-PhCN)4(OTf)2. We anticipate that the bench-stable and inexpensive Ni(OTf)2, coupled with little to no extra laboratory training to set up the glycosylation reaction and no requirement of specialized equipment, should make this methodology be readily adopted by non-carbohydrate specialists. This report further highlights the efficacy of Ni(OTf)2to prepare several bioactive motifs, such as blood type A-type V and VI antigens, heparin sulfate disaccharide repeating unit, aminooxy glycosides, and α-GalNAc-Serine conjugate, which cannot be achieved in high yield and α-selectivity utilizing in-house prepared Ni(4-F-PhCN)4(OTf)2catalyst. The newly-developed protocol eliminates the need for the synthesis of Ni(4-F-PhCN)4(OTf)2and is scalable and reproducible. Furthermore, computational simulations in combination with1H NMR studies analyzed the effects of various solvents on the intramolecular hydrogen bonding network of tumor-associated mucin Fmoc-protected GalNAc-threonine amino acid antigen derivative, verifying discrepancies found that were previously unreported.
Department of Chemistry, University of Iowa, Iowa City, 52242, USA.
Eric T
ET
Sletten
Iowa Informatics Initiative, University of Iowa, Iowa City, 52242, USA.
Sai Kumar
SK
Ramadugu
Department of Chemistry, University of Iowa, Iowa City, 52242, USA. Electronic address: hien-nguyen@uiowa.edu.
Hien M
HM
Nguyen
D000617:Aminoglycosides / Q000138:chemical synthesis* / Q000737:chemistry; D002384:Catalysis; D006031:Glycosylation; D006860:Hydrogen Bonding; D015394:Molecular Structure; D009532:Nickel / Q000737:chemistry*; D013237:Stereoisomerism
D000617:Aminoglycosides; D009532:Nickel