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Synthesis of disaccharide neu5Gcα(2–6)galNAcα as a spacer glycoside

Abstract

The first synthesis of the Neu5Gc analogue of SiaT n disaccharide, which can be detected in breast tumors by immunochemical methods, is reported. The regioselective sialylation of (3-trifluoroacetamidopropyl)-2-azido-2-deoxy-α-D-galactopyranoside with peracetate of the methyl ester ofN-acetoxyacetyl-neuraminic acid β-ethylthioglycoside in the presence ofN-iodosuccinimide and trifluoromethanesulfonic acid (or its trimethylsilyl ester) resulted in the derivatives of α- and β-sialyl(2→6)galactosaminide in 39 and 32% yields, respectively. The catalytic hydrogenolysis of the azido group and subsequentN- andO-acetylation of the α-anomer gave the peracetate of trifluoroacetamidopropyl glycoside. Removal of the protective groups led to glycoside Neu5Gcα2→6GalNAcα-O(CH2)3NH2. Using the Neu5Gc derivative with acetoxyacetyl groups at positions O9 and O4 as a donor increases the α-selectivity of sialylation to afford the α- and β-anomers in 69 and 8% yields, respectively.

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Abbreviations

FAB-MS:

fast atom bombardment mass spectrometry

Neu5Ac:

N-acetylneuraminic acid

Neu5Gc:

N-glycolylneuraminic acid

NIS:

N-iodosuccinimide

SpOH:

HO(CH2)3NHCOCF3

TfOH:

trifluoromethanesulfonic acid

TMS-OTf:

trifluoromethanesulfonic acid trimethylsilyl ester

TOF-MS:

252Cf plasma desorption time-of-flight mass spectrometry

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Correspondence to N. E. Byramova.

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Simeoni, L.A., Byramova, N.E. & Bovin, N.V. Synthesis of disaccharide neu5Gcα(2–6)galNAcα as a spacer glycoside. Russ J Bioorg Chem 26, 183–191 (2000). https://doi.org/10.1007/BF02786344

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  • DOI: https://doi.org/10.1007/BF02786344

Key words

  • N-acetylneuraminic acid
  • N-glycolylneuraminic acid
  • Sia(Gc)Tn antigen
  • sialosides
  • sialylation
  • thioglycosides