Chemical synthesis of the O-linked hexasaccharide of Trypanosoma cruzi mucins using superarmed donors

GUSTAVO A. KASHIWAGI; VERÓNICA M. MENDOZA; CARMEN R. CORI CALIZAYA; ROSA M. DE LEDERKREMER; CAROLA GALLO-RODRIGUEZ

CABA

Simposio; First Argentinian Symposium of Glycobiology; 2014

Fundacion Instituto Leloir-IFIBYNE-IBYME

Trypanosoma cruzi, the etiologic agent of Chagas disease, presents in its external surface the enzyme trans-sialidase (TcTs) and mucin-type glycoproteins, which are involved in the infection process. Sialic acid is transferred from the host oligosaccharides to the mucin oligosaccharides. We have undertaken the chemical synthesis of the mucin oligosaccharides, in particular of those containing Galf. We here describe the synthesis of the hexasaccharide b-D-Galp-(1-2)-[b-D-Galp-(1-3)]-b-D-Galp-(1-6)-[b-D-Galp(1-2)-b-D-Galf(1-4)]-D-GlcNAc (1). In this case, a [3+3] convergent glycosylation strategy, successfully used for the synthesis of the analogous b-D-Galf(1-2)-b-D-Galf(1-4)-containing hexasaccharide, was employed. The trisaccharide derivative b-D-Galp-(1-2)-b-D-Galf-(1-4)-D-GlcNAc (2) was synthesized from the reducing end to the non-reducing end in order to obtain the b-D-Galp-(1-2)-b-D-Galf linkage diastereoselectively. Several Galp donors were essayed, however, only the superarmed donor, tolyl 2-O-benzoyl-3,4,6-tri-O-benzyl-1-thio-b-D-galactopyranoside, allowed the introduction of the Galp. Surprisingly, diastereomeric mixtures were obtained in spite of the presence of a participant group in O-2. Sodium borohydride reduction of hexasaccharide 1 gave the alditol with identical spectroscopic data compared to the alditol isolated by reductive b-elimination from T. cruzi mucins.