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Replacement of the L-iduronic acid unit of the anticoagulant pentasaccharide idraparinux by a 6-deoxy-L-talopyranose – Synthesis and conformational analysis

Demeter, Fruzsina and Gyöngyösi, Tamás and Bereczky, Zsuzsanna and E. Kövér, Katalin and Herczeg, Mihály and Borbás, Anikó (2018) Replacement of the L-iduronic acid unit of the anticoagulant pentasaccharide idraparinux by a 6-deoxy-L-talopyranose – Synthesis and conformational analysis. SCIENTIFIC REPORTS, 8. p. 13736. ISSN 2045-2322

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Abstract

One critical part of the synthesis of heparinoid anticoagulants is the creation of the L-iduronic acid building block featured with unique conformational plasticity which is crucial for the anticoagulant activity. Herein, we studied whether a much more easily synthesizable sugar, the 6-deoxy-L-talose, built in a heparinoid oligosaccharide, could show a similar conformational plasticity, thereby can be a potential substituent of the L-idose. Three pentasaccharides related to the synthetic anticoagulant pentasaccharide idraparinux were prepared, in which the L-iduronate was replaced by a 6-deoxy- L-talopyranoside unit. The talo-configured building block was formed by C4 epimerisation of the commercially available L-rhamnose with high efficacy at both the monosaccharide and the disaccharide level. The detailed conformational analysis of these new derivatives, differing only in their methylation pattern, was performed and the conformationally relevant NMR parameters, such as proton-proton coupling constants and interproton distances were compared to the corresponding ones measured in idraparinux. The lack of anticoagulant activity of these novel heparin analogues could be explained by the biologically not favorable 1C4 chair conformation of their 6-deoxy-L-talopyranoside residues.

Item Type: Article
Subjects: Q Science / természettudomány > QD Chemistry / kémia > QD04 Organic chemistry / szerves kémia
Depositing User: Dr. Mihály Herczeg
Date Deposited: 17 Sep 2018 07:23
Last Modified: 17 Sep 2018 07:23
URI: http://real.mtak.hu/id/eprint/84157

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