Synthesis of the O-linked hexasaccharide containing β-D-Galf-(1→2)-β-D-Galf in Trypanosoma cruzi mucins.
The hexasaccharide β-D-Galp-(1→2)-[β-D-Galp-(1→3)]-β-D-Galp-(1→6)-[β-D-Galf(1→2)-β-D-Galf(1→4)]-D-GlcNAc (1) is the largest carbohydrate structure released as alditol by reductive β-elimination from mucins of some strains of T. cruzi. The terminal β-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 β-D-Galf-(1→2)-β-D-Galf-D-GlcNAc synthon was sequentially constructed from the reducing end to the non-reducing end employing benzyl α-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-β(1→4)-GlcNAc linkage by the trichloroacetimidate method of glycosylation was achieved. The (1)H NMR spectrum of alditol 2 was identical to the product released by β-elimination from the parasite mucin.
CIHIDECAR, Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pabellón II, 1428 Buenos Aires, Argentina.
Gustavo A
GA
Kashiwagi
Verónica M
VM
Mendoza
Rosa M
RM
de Lederkremer
Carola
C
Gallo-Rodriguez
D002240:Carbohydrate Sequence; D005690:Galactose / Q000138:chemical synthesis / Q000737:chemistry; D006031:Glycosylation; D008969:Molecular Sequence Data; D009077:Mucins / Q000737:chemistry*; D009844:Oligosaccharides / Q000138:chemical synthesis* / Q000737:chemistry; D015800:Protozoan Proteins / Q000737:chemistry*; D013402:Sugar Alcohols / Q000138:chemical synthesis / Q000737:chemistry; D014349:Trypanosoma cruzi / Q000737:chemistry*
D009077:Mucins; D009844:Oligosaccharides; D015800:Protozoan Proteins; D013402:Sugar Alcohols; D005690:Galactose