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

KASHIWAGI, GUSTAVO; MENDOZA, VM; MUCHNIK DE LEDERKREMER, R; GALLO-RODRIGUEZ, C.

ORGANIC & BIOMOLECULAR CHEMISTRY

ROYAL SOC CHEMISTRY

Lugar: CAMBRIDGE; Año: 2012 vol. 10 p. 6322 - 6332

1477-0520

The hexasaccharide b-D-Galp-(1?¨2)-[b-D-Galp-(1?¨3)]-b-D-Galp-(1?¨6)-[b-D-Galf(1?¨2)-b-D-Galf(1?¨4)]-D-GlcNAc (1) is the largest carbohydrate structure released as alditol by reductive b-elimination from mucins of some strains of T. cruzi. The terminal b-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 b-D-Galf-(1?¨2)-b-D-Galf-D-GlcNAc synthon was sequentially constructed from the reducing end to the non-reducing end employing benzyl a-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-b(1?¨4)GlcNAc linkage by the trichloroacetimidate method of glycosylation was achieved. The 1H NMR spectrum of alditol 2 was identical to the product released by b-elimination from the parasite mucin.