One-Pot Glycosylation Strategy Assisted by Ion Mobility-Mass Spectrometry Analysis toward the Synthesis of N-Linked Oligosaccharides

N-Glycans are major constituents of several cellular glycoproteins. One-pot strategies for the synthesis ofN-glycans arecrucial for the rapid generation of pure samples to determine theirbiological functions. Herein, we describe a double one-pot strategyfor the synthesis ofN-glycans assisted by an IM-MS analysisapproach for rapid screening of optimized glycosylation reactionconditions. This research includes triflate-mediated direct beta-mannosylation and tandem glycosylation in a one-pot strategy forthe synthesis of the challengingN-linked trisaccharide core beta-5.Furthermore, a one-pot sequential glycosylation of theN-linkedtrisaccharide core7furnishes diverse high-mannose typeN-glycanswith excellent stereo- and regioselectivities. In particular, ionmobility-mass spectrometry-based quantitative analysis is appliedto identify the stereo- and regioselective outcomes of the crude reaction mixtures to develop a highly efficient one-pot protocol.

Automated summary

This study describes a double one-pot strategy for the synthesis of N-glycans, assisted by an IM-MS analysis approach for rapid screening of optimized glycosylation reaction conditions. The method enables the efficient synthesis of high-mannose type N-glycans with excellent stereo- and regioselectivities.