Multisite Partial Glycosylation Approach for Preparation of Biologically Relevant Oligomannosyl Branches Contribute...

High-mannose-type glycans play essential biological roles, e.g., immune response and glycoprotein quality control, and preparing a series of oligomannosyl branches of high-mannose-type glycans is critical for biological studies. However, obtaining sufficient amounts of the various oligomannosyl branches is challenging. In this study, we demonstrated a partial glycosylation strategy for the single-step synthesis of various biologically relevant oligomannosyl-branched structures. First, Manα1-6(Manα1-3)Man-type oligomannosyl branch was synthesized via double glycosylation from a 3,6-di-OH mannosyl acceptor and fluorinated mannosyl donor with perfect α-selectivity. Subsequent partial glycosylation by reducing the equivalent of the mannosyl donor enabled to obtain biologically relevant Manα1-2Manα1-6(Manα1-2Manα1-3)Man, Manα1-6(Manα1-2Manα1-3)Man, Manα1-2Manα1-6(Manα1-3)Man, and Manα1-6(Manα1-3)Man in one-pot. Each oligomannosyl branch could be easily purified by liquid chromatography. The resulting structural isomers were identified by 2D-HMBC NMR. A systematic lectin affinity assay using the prepared oligomannosyl branches showed different specificities for the Galanthus nivalis lectin between structural isomers of the oligomannosyl branches with the same number of mannose residues..