Iterative One-Pot [alpha]-Glycosylation Strategy: Application to Oligosaccharide Synthesis

• Published in: Advanced synthesis & catalysis 2012-11, Vol.354 (17), p.3299-3310
• Main Authors: Liu, Chih-Yueh Ivan, Mulani, Shaheen, Mong, Kwok-Kong Tony
• Format: Article
• Language: English
• Subjects: Bonding
• ISSN: 1615-4150; 1615-4169
• DOI: 10.1002/adsc.201200396

Based on the combined use of dimethylformamide (DMF) modulation and neighboring group participation, three iterative one-pot [alpha]-glycosylation methods, i.e., one-pot ([alpha],[alpha])-, one-pot ([beta],[alpha])-, and one-pot ([alpha],[beta])-glycosylations, were developed. These methods are applicable to a range of thioglycosyl donors, confer stereocontrol in [alpha]-/[beta]-glycosidic bond formation, and thus provide for rapid access to oligosaccharides with various permutations of anomeric configurations. The utility of these one-pot glycosylation methods is demonstrated in the synthesis of eight non-natural and natural oligosaccharide targets, including the core 1 serine conjugate, core 8 serine conjugate, the D-Gal-[alpha](1 arrow right 3)-D-Glc-[alpha](1 arrow right 3)-L-Rha trisaccharide unit of the cell wall component in Streptococcus pneumoniae, and the D-Glc-[alpha](1 arrow right 2)-D-Glc-[alpha](1 arrow right 3)-D-Glc trisaccharide terminus of the N-linked glycan precursor. Confirmation of the anomeric configurations of these oligosaccharides is evidenced by super(1)H, super(13)C, super(13)C-non-proton decoupling, and heteronuclear correlation 2D NMR experiments. Global deprotection of selected oligosaccharide targets is illustrated.