A Single Route to Mammalian N-Glycans Substituted with Core Fucose and Bisecting GlcNAc

The occurrence of alpha 1,6-linked core fucose on the N-glycans of mammalian glycoproteins is involved in tumor progression and reduces the bioactivity of antibodies in antibody-dependent cell-mediated cytotoxicity (ADCC). Since core-fucosylated N-glycans are difficult to isolate from natural sources, only chemical or enzymatic synthesis can provide the desired compounds for biological studies. A general drawback of chemical alpha-fucosylation is that the chemical assembly of alpha 1,6-linked fucosides is not stereospecific. A robust and general method for the alpha-selective fucosylation of acceptors with primary hydroxy groups in alpha/ratios exceeding 99:1 was developed. The high selectivities result from the interplay of an optimized protecting group pattern of the fucosyl donors in combination with the activation principle and the reaction conditions. Selective deprotection yielded versatile azides of all mammalian complex-type core-fucosylated N-glycans with 2-4 antennae and optional bisecting GlcNAc.