Large-scale synthesis of 6-deoxy-6-sulfonatomethyl glycosides and their application for novel synthesis of a heparinoid pentasaccharide trisulfonic acid of anticoagulant activity

Erika Mező; Mihály Herczeg; Dániel Eszenyi; Anikó Borbás

doi:10.1016/j.carres.2014.02.012

Large-scale synthesis of 6-deoxy-6-sulfonatomethyl glycosides and their application for novel synthesis of a heparinoid pentasaccharide trisulfonic acid of anticoagulant activity

Carbohydr Res. 2014 Mar 31:388:19-29. doi: 10.1016/j.carres.2014.02.012. Epub 2014 Feb 18.

Authors

Erika Mező¹, Mihály Herczeg², Dániel Eszenyi¹, Anikó Borbás³

Affiliations

¹ Department of Pharmaceutical Chemistry, Medical and Health Science Center, University of Debrecen, PO Box 70, H-4010 Debrecen, Hungary; Department of Organic Chemistry, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.
² Department of Organic Chemistry, University of Debrecen, PO Box 20, H-4010 Debrecen, Hungary.
³ Department of Pharmaceutical Chemistry, Medical and Health Science Center, University of Debrecen, PO Box 70, H-4010 Debrecen, Hungary. Electronic address: borbas.aniko@pharm.unideb.hu.

PMID: 24607537
DOI: 10.1016/j.carres.2014.02.012

Abstract

Multigram-scale syntheses of three 6-deoxy-6-sulfonatomethyl α-glucosides were accomplished via reactions of the corresponding primary triflate derivatives with the lithiated ethyl methanesulfonate. Chemoselective glycosylation reactions of different 6-C-sulfonatomethyl glucoside donors were studied. The sulfonic acid-containing building blocks were utilised in a novel [2+3] block synthesis of a trisulfonic acid isoster of the anticoagulant pentasaccharide idraparinux.

Keywords: Aglycon transfer; Anticoagulation; Chemoselective glycosylation; Pentasaccharide; Sulfonic acid; Uronic acids.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anticoagulants / chemical synthesis*
Carbohydrate Sequence
Glycosides / chemical synthesis*
Glycosylation
Heparinoids / chemical synthesis*
Molecular Sequence Data
Oligosaccharides / chemical synthesis*
Sulfonic Acids / chemical synthesis*
Uronic Acids / chemistry

Substances

Anticoagulants
Glycosides
Heparinoids
Oligosaccharides
Sulfonic Acids
Uronic Acids