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Synthesis, conformation and biology of naphthoxylosides
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2011 (English)In: Bioorganic & Medicinal Chemistry, ISSN 0968-0896, E-ISSN 1464-3391, Vol. 19, no 13, 4114-4126 p.Article in journal (Refereed) Published
Abstract [en]

Proteoglycans (PG) are polyanionic proteins consisting of a core protein substituted with carbohydrate chains, that is, glycosaminoglycans (GAG). The biosynthesis of GAG can be manipulated by simple xylosides carrying hydrophobic aglycons, which can enter the cell and initiate the biosynthesis. While the importance of the aglycon is well investigated, there is far less information on the effect of modifications in the xylose residue.

We have developed a new synthetic protocol, based on acetal protection and selective benzylation, for modification of the three hydroxyl groups in xylose. Thus we have synthesized twelve analogs of 2-naphthyl β-d-xylopyranoside (XylNap), where each hydroxyl group has been epimerized or replaced by methoxy, fluoro, or hydrogen.

To gain more information about the properties of xylose, conformational studies were made on some of the analogs. It was found that the 4C1 conformation is highly predominant, accompanied by a nonnegligible population of the 2S0 conformation. However, deoxygenation at C3 results in a large portion of the 1C4 conformation.

The GAG priming ability and proliferation activity of the twelve analogs, were investigated using a matched pair of human breast fibroblasts and human breast carcinoma cells. None of the analogs initiated the biosynthesis of GAG, but an inhibitory effect on endogenous PG production was observed for analogs fluorinated or deoxygenated at C4. From our data it seems reasonable that all three hydroxyl groups in XylNap are essential for the priming of GAG chains and for selective toxicity for tumor cells.

Place, publisher, year, edition, pages
2011. Vol. 19, no 13, 4114-4126 p.
Keyword [en]
Naphthoxylosides, synthesis, conformational analysis, antiproliferative activity, tumor cells, glycosaminoglycan
National Category
Organic Chemistry
URN: urn:nbn:se:su:diva-59713DOI: 10.1016/j.bmc.2011.05.007ISI: 000291934700027OAI: diva2:429951
Swedish Research CouncilKnut and Alice Wallenberg Foundation
Available from: 2011-07-06 Created: 2011-07-06 Last updated: 2013-08-19Bibliographically approved
In thesis
1. Structure, dynamics and reactivity of carbohydrates: NMR spectroscopic studies
Open this publication in new window or tab >>Structure, dynamics and reactivity of carbohydrates: NMR spectroscopic studies
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The main focus of this thesis is on the ring conformations of carbohydrate molecules; how the conformational equilibria and the rates of the associated interconversions are affected by the molecular constitution and their surroundings.

The conformational equilibria of a group of amine linked pseudodisaccharides, designed as potential glycosidase inhibitors, comprising α-D-altrosides are described in Chapter 3. The OS2 conformation was largely populated, and the ring conformation was found to depend on the charge of the amine functionality.

The conformations of β-D-xylopyranoside derivatives with naphthyl-based aglycones, which are potential anti-cancer agents, are described in chapter 4. Solvent dependent flexibility was observed. Intramolecular hydrogen bonds were concluded to be involved in the stabilization of 1C4 conformers in non-hydrogen bonding solvents of low polarity.

Chapter 5 describes the first measurements of the conformational exchange rates of mannuronic acid ester derivatives between the 4C1 and 1C4 conformations, through DNMR measurements. The relative reactivity of glycosyl triflates as electrophiles in glycosylation reactions were investigated with NMR-based competition experiments.

In Chapter 6, investigations of ruthenium-catalyzed epimerizations of the allylic alcohols of glycal derivatives, and stereoselective synthesis of esters through a DYKAT protocol, are described. The kinetics of the epimerizations were elaborated through different NMR-spectroscopic methods.

Chapter 7 describes additions of NMR chemical shift data of mono- and oligosaccharides to database of the computer program CASPER, and applications thereof.

Place, publisher, year, edition, pages
Stockholm: Department of Organic Chemistry, Stockholm University, 2013. 67 p.
Carbohydrates, Conformation, NMR spectroscopy, Hydrogen bond
National Category
Organic Chemistry
Research subject
Organic Chemistry
urn:nbn:se:su:diva-92408 (URN)978-91-7447-730-6 (ISBN)
Public defence
2013-09-20, Magnélisalen, Kemiska Övningslaboratoriet, Svante Arrhenius väg 16 B, Stockholm, 10:00 (English)

At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 4: Submitted. Paper 5: Manuscript.

Available from: 2013-08-29 Created: 2013-08-02 Last updated: 2016-04-11Bibliographically approved

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Rönnols, JerkWidmalm, Göran
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