Pondering the Structural Factors that Affect 1,2-trans-Galactosylation: A Lesson Learnt from 3-O-β-Galactosylation of Galactosamine.

Stereoselective formation of glycosidic bonds remains one of the most challenging topics in carbohydrate chemistry. The predominant method for stereoselective construction of 1,2-trans-glycosidic bonds is through the neighboring group participation effect (NGPE), which proved to be less successful in synthesizing Galβ(1→3)GalNAc disaccharide. The steric effect that overshadows NGPE and the impacts of substituents at the 3-O- and 2-N-positions of donors and acceptors, respectively, on this synthesis were systematically examined to lead to some practical guidelines for choosing protecting groups towards the successful synthesis of Galβ(1→3)GalNAc and similar disaccharides.