Novel triazolyl macrocycles incorporating glycolipids: a new protocol

Six new macrocycles incorporating glycolipids containing one triazole ring in their structures were synthesized via intramolecular macrocyclic closure. The synthesis strategy is based on the different reactivities of primary and secondary hydroxyl groups on the monosaccharides. The protecting of hydroxyls on 4,6-positions by benzylidene, followed by benzylation of 2,3-positions and removal of the benzylidene, selectively left over the free secondary and primary hydroxyl on 4- and 6-carbons, respectively. The selective tosylation on the primary hydroxyl group followed by azide replacement prepares the first functionality of the glycolipids on carbon number 6 (C-6) on the ring of monosaccharide moieties. Subsequently, the nucleophilic displacement of suitable ethylene glycolic propargyl on the carbon number 4 (C-4) makes the intramolecular 1,3-dipolar ring closure assisted via copper(I)-catalyzed azide-alkyne cycloaddition to be possible. All reaction conditions of 1,3-dipolar ring closures, including time, catalyst, temperature, and solvent, have been optimized.