Stereoselective synthesis of LacdiNAc N-glycan based on remote neighboring group participation

LacdiNAc (GalNAcβ1-4GlcNAc) is a distinctive epitope found at the non-reducing termini of both N- and O-glycans. In recent years, the physiological functions of LacdiNAc have attracted increasing attention. Consequently, there is a significant demand for pure glycans for use in biochemical experiments. In this study, a concise and practical synthetic approach was developed for biantennary complex-type nonasaccharide 1, which contains LacdiNAc structures at the non-reducing end. Specifically, nonasaccharide 2 was initially constructed in a stereoselective manner via the condensation of trisaccharide donor 3 with trisaccharide acceptor 4, which bears hydroxy groups at the 3- and 6-positions of the β-mannose residue. Notably, this was achieved via the remote neighboring group participation of a pivaloyl group. Subsequent conversion of the N-phthalimido group into an acetamido group, followed by global deprotection, furnished the target compound, 1. The developed synthetic route represents a valuable tool for future investigations into LacdiNAc-modified N-glycans.