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Pre‐Activation‐Based One‐Pot Synthesis of an α‐(2,3)‐Sialylated Core‐Fucosylated Complex Type Bi‐Antennary N‐Glycan Dodecasaccharide
Author(s) -
Sun Bin,
Srinivasan Balasubramanian,
Huang Xuefei
Publication year - 2008
Publication title -
chemistry – a european journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.687
H-Index - 242
eISSN - 1521-3765
pISSN - 0947-6539
DOI - 10.1002/chem.200800757
Subject(s) - chemistry , glycan , disaccharide , glycosylation , tetrasaccharide , stereochemistry , acceptor , oligosaccharide , mannose , combinatorial chemistry , biochemistry , glycoprotein , polysaccharide , physics , condensed matter physics
Synthesis of N‐glycans is of high current interests due to their important biological properties. A highly efficient convergent strategy based on the pre‐activation method for assembly of the complex type core fucosylated bi‐antennary N‐glycan dodecasaccharide has been developed. Retrosynthetically, this extremely challenging target is broken down to three modules: a sialyl disaccharide, a glucosamine building block and a hexasaccharide diol acceptor. The sialyl disaccharide was easily obtained by selective activation of a new 5‐ N ‐trichloroacetyl protected sialyl donor in the presence of a thiogalactoside acceptor. The hexasaccharide diol module was produced by double mannosylation of a fucosylated tetrasaccharide acceptor, which in turn was generated by glycosylation of a α‐fucosylated disaccharide with a β‐mannose containing disaccharide donor. The union of the three modules was performed in one‐pot giving the fully protected dodecasaccharide in high yield. This synthesis is characterized by minimum protective group and aglycon adjustment on oligosaccharide intermediates, thus greatly enhancing the overall synthetic efficiency. The modular feature of this strategy suggests that this method can be readily adapted to the synthesis of a wide variety of N‐glycan structures.