New synthesis of idraparinux, the non-glycosaminoglycan analogue of the antithrombin-binding domain of heparin

Mihály Herczeg, Erika Mezo, Dániel Eszenyi, S. Antus, A. Borbás

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Idraparinux, the fully O-sulfated, O-methylated, heparin-related pentasaccharide possessing selective factor Xa inhibitory activity, was prepared by a new synthetic pathway. This route was based on a [2+3] block synthesis utilizing a 6-O-silyl-protected l-idose-containing trisaccharide acceptor, which was glycosylated with a disaccharide donor containing a non-oxidized precursor of the glucuronic acid. The unique strategy of multiple functionalizations at pentasaccharide levels, involving triple methylation followed by oxidation of the glucose and the idose precursors into d-glucuronic and l-iduronic acids in one step, proved to be highly efficient, providing the target pentasaccharide through a 39-step synthesis starting from d-glucose and methyl α-d-glucopyranoside.

Original languageEnglish
Pages (from-to)2919-2927
Number of pages9
JournalTetrahedron
Volume70
Issue number18
DOIs
Publication statusPublished - May 6 2014

Fingerprint

Antithrombins
Heparin
Iduronic Acid
Trisaccharides
Glucose
Glucuronic Acid
Factor Xa
Methylation
Disaccharides
Oxidation
idose
idraparinux
IC 831423

Keywords

  • Anticoagulation
  • Glycosylation reactions
  • Heparinoid pentasaccharide
  • Multiple functionalization
  • Orthogonal protecting groups
  • Uronic acids

ASJC Scopus subject areas

  • Biochemistry
  • Organic Chemistry
  • Drug Discovery

Cite this

New synthesis of idraparinux, the non-glycosaminoglycan analogue of the antithrombin-binding domain of heparin. / Herczeg, Mihály; Mezo, Erika; Eszenyi, Dániel; Antus, S.; Borbás, A.

In: Tetrahedron, Vol. 70, No. 18, 06.05.2014, p. 2919-2927.

Research output: Contribution to journalArticle

Herczeg, Mihály ; Mezo, Erika ; Eszenyi, Dániel ; Antus, S. ; Borbás, A. / New synthesis of idraparinux, the non-glycosaminoglycan analogue of the antithrombin-binding domain of heparin. In: Tetrahedron. 2014 ; Vol. 70, No. 18. pp. 2919-2927.
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