CONICET | Buscador de Institutos y Recursos Humanos

The mucin-like glycoproteins are major components in the surface of Trypanosoma cruzi, the agent of American trypanosomiasis.1 The oligosaccharides in the mucins are O-linked to the protein and may be derived from two cores, Galp(b1®4)-GlcNAc or Galf(b1®4)-GlcNAc. The cores are further branched by Galf or Galp. The terminal b-Galp residues are acceptors of sialic acid in the trans-sialidase reaction, involved in the invasion of the host cells. The presence of b-Galf is related to the lineage of the T. cruzi strain. In our laboratory we have undertaken the chemical synthesis of the Galf-containing oligosaccharides,2 with the aim to correlate their structure with the ability to act as substrates in the reaction of trans-sialidation. Recently, the novel trisaccharide alditol, b-D-Galf(1®2)-b-D-Galf(1®4)-D-GlcNAc-ol, was isolated from the Tulahuen strain by reductive b-elimination.3 Moreover, this structure is part of the hexasaccharide alditol, acceptor of sialic acid, obtained from mucins of the Tulahuen and G strains. We now report advances in the synthesis of Galf(b1®2)-Galf(b1®4)-GlcNAc (1). The synthetic strategy relied on the use of a convenient derivative of D-galactono-1,4-lactone as precursor of the internal galactofuranose unit. Glycosylation of acceptor 2 with penta-O-benzoyl-a,b-D-galactofuranose promoted by SnCl4, afforded the b(1®2) disaccharide lactone 4 diastereoselectively in 92% yield. Further reduction of the lactone function of 4 with diisoamylborane gave Galf(b1®2)-D-Galf (5, 71 %). Activation of 5 via trichloroacetimidate (81 %) and subsequent glycosylation with benzyl 2-acetamido-3-O-benzoyl-6-O-t-butyldiphenylsilyl-2-deoxy-a-D-glucopyranoside (6) in CH2Cl2 with TMSOTf as catalyst gave the desired compound 7 (35 %). The a(1®4) product (10%) was also obtained due to the absence of a neighbour participating group in 5.

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