Synthesis of the O-linked hexasaccharide containing β-D-Galf-(1→2)-β-D-Galf in Trypanosoma cruzi mucins

The hexasaccharide beta-D-Galp-(1 -> 2)-[beta-D-Galp-(1 -> 3)]-beta-D-Galp-(1 -> 6)-[beta-D-Galf(1 -> 2)-beta-D-Galf(1 -> 4)]-D-GlcNAc (1) is the largest carbohydrate structure released as alditol by reductive beta-elimination from mucins of some strains of T. cruzi. The terminal beta-D-Galp units are sites of sialylation by trans-sialidase which transfers sialic acid from the host to the parasite. Hexasaccharide 1 was synthesized by a [3 + 3]-convergent strategy based on a nitrile assisted glycosylation, using the trichloroacetimidate method. The beta-D-Galf-(1 -> 2)-beta-D-Galf-D-GlcNAc synthon was sequentially constructed from the reducing end to the non-reducing end employing benzyl alpha-D-galactofuranoside as starting material for the internal Galf unit. The choice of this novel precursor, obtained in one-reaction step from galactose, allowed the introduction of an orthogonal and participating levulinoyl group at O-2. Thus, the diastereoselective construction of the Galf-beta(1.4)-GlcNAc linkage by the trichloroacetimidate method of glycosylation was achieved. The H-1 NMR spectrum of alditol 2 was identical to the product released by beta-elimination from the parasite mucin.