A Double Regio‐ and Stereoselective Glycosylation Strategy for the Synthesis of N‐Glycans

A building block approach for biantennary N‐linked oligosaccharides from glycoproteins (N‐glycans) has been developed. Starting from a core trisaccharide (β‐mannosyl chitobiose) containing a benzylidene‐protected β‐mannoside, the attachment of the disaccharide building blocks for the antennae can be performed in a double regio‐ and stereoselective manner. A short synthesis of a GlcNPhtβ1,2Man donor was developed. The benzylidene acetal moiety, as a minimal protection of the β‐mannoside, allows selective α‐glycosylation at OH‐3 of the 2,3‐diol with GlcNβ1,2Man trichloroacetimidate donors. Subsequent debenzylidenation leads to a 4,6‐diol, which can be selectively extended at OH‐6. Overreaction at OH‐4 was generally low when phthalimido‐protected donors were used. This general strategy represents a modular synthesis of N‐glycans and their glycoconjugates.