Rapid Access to Human Milk Oligosaccharide Analogues through a Partially Protected N-Acetylglucosamine Donor.

Access to structurally defined human milk oligosaccharides (HMOs) remains nontrivial because chemical synthesis often relies on extensive protecting-group manipulations. Here, we report a gold(I)-catalyzed, protecting-group-minimized approach to HMO-related tri- and tetrasaccharides using a partially protected 2-acetamido-2-deoxy glycosyl donor. Efficient formation of the β-GlcNAc-(1→3)-Gal motif was found to depend strongly on the protecting-group pattern of the galactosyl acceptor, with a 2-O-benzyl group being crucial for productive glycosylation. Subsequent Au(I)-catalyzed site-selective 3'-O-glycosylation and further reducing-end elaboration enabled rapid diversification of the core disaccharide.