Glycosylation of ‘basic’ alcohols: methyl 6-(hydroxymethyl)picolinate as a case study

Glycosylation is promoted by acid promoters rendering the reactions with basic acceptors challenging. This report presents an in depth study involving methyl 6-(hydroxymethyl)picolinate as the model acceptor and 22 glycosyl donors to afford the desired glycosides in good yields ranging from 46% to 85%. Several parameters were evaluated, including the protecting groups of the glycosyl donor, the leaving group at the anomeric center, and the promoter. The influence of the pyridine ring was evident with a benzene-based acceptor affording high yields of glycoside (79%) in comparison to the pyridine-based acceptor (46%). The present work provides a general and reliable access to pyridine-containing glycosides.

Graphical abstractFigure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Glycosylation of pyridine-containing alcohols is challenging. ► Pyridine is quenching with the acid promoter and excess of promoter is required. ► Glycosylation conditions could be determined for galactose (α and β), N-acetylglucosamine, glucose, mannose, fucose, rhamnose, and lactose.