129729-40-4Relevant articles and documents
Nickel-catalyzed stereoselective glycosylation with C(2)- N-substituted benzylidene d-glucosamine and galactosamine trichloroacetimidates for the formation of 1,2-cis-2-amino glycosides. applications to the synthesis of heparin disaccharides, GPI anchor pseudodisaccharides, and α-GalNAc
Mensah, Enoch A.,Yu, Fei,Nguyen, Hien M.
supporting information; experimental part, p. 14288 - 14302 (2010/12/19)
The 1,2-cis-2-amino glycosides are key components found within a variety of biologically important oligosaccharides and glycopeptides. Although there are remarkable advances in the synthesis of 1,2-cis-2-amino glycosides, disadvantages of the current state-of-the-art methods include limited substrate scope, low yields, long reaction times, and anomeric mixtures. We have developed a novel method for the synthesis of 1,2-cis-2-amino glycosides via nickel-catalyzed α-selective glycosylation with C(2)-N-substituted benzylidene d-glucosamine and galactosamine trichloroacetimidates. These glycosyl donors are capable of coupling to a wide variety of alcohols to provide glycoconjugates in high yields with excellent levels of α-selectivity. Additionally, only a substoichiometric amount of nickel (5-10 mol %) is required for the reaction to occur at 25 °C. The current nickel method relies on the nature of the nickel-ligand complex to control the α-selectivity. The reactive sites of the nucleophiles or the nature of the protecting groups have little effect on the α-selectivity. This methodology has also been successfully applied to both disaccharide donors and acceptors to provide the corresponding oligosaccharides in high yields and α-selectivity. The efficacy of the nickel procedure has been further applied toward the preparation of heparin disaccharides, GPI anchor pseudodisaccharides, and α-GluNAc/GalNAc. Mechanistic studies suggest that the presence of the substituted benzylidene functionality at the C(2)-amino position of glycosyl donors is crucial for the high α-selectivity observed in the coupling products. Additionally, the α-orientation of the C(1)-trichloroacetimidate group on glycosyl donors is necessary for the coupling process to occur.
Nickel-catalyzed stereoselective formation of α-2-deoxy-2-amino glycosides
Mensah, Enoch A.,Nguyen, Hien M.
supporting information; experimental part, p. 8778 - 8780 (2009/12/04)
(Chemical Equation Presented) The development of a new method for the stereoselective synthesis of α-2-deoxy-2-amino glycosides is described. This methodology relies on the nature of the cationic nickel catalyst, generated in situ from LnNiCl2 and AgOTf, to direct the anomeric stereoselectivity. The new glycosylation reaction is highly α-selective and proceeds under mild conditions with 5-10 mol % of the nickel catalyst loading at ambient temperature. This new method has been applied to both D-glucosamine and galactosamine trichloroacetimidate donors as well as an array of primary, secondary, and tertiary alcohol nucleophiles to provide the desired glycoconjugates in good yields with excellent α-selectivity. Mechanistic studies of the present reaction are underway and will be reported in due course. Copyright
