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Synthesis of 1’-(saccharide)substituted 28-O-(1’H-[1’,2’,3’]triazolyl-4’-methyl) derivatives of protoescigenin

Mariusz M. Gruza 1Kamil Jatczak 1Katarzyna Komor 2Piotr Świerk 2Wiesław Szeja 2Grzegorz Grynkiewicz 1

1. Pharmaceutical Research Institute (IF), Rydygiera 8, Warszawa 01-793, Poland
2. Silesian University of Technology, Department of Organic Chem., Bioorganic Chem. and Biotechnol., Krzywoustego 4, Gliwice 44-100, Poland

Selective functionalization of protoescigenin [1,2]: 3,16,21,22,24,28-hexahydroxy-olean-12-ene 1, either directly, or by application of protective group strategy, proved unexpectedly difficult. Since various approaches to glycosylation of 1 or its partially protected derivatives have failed [3,4,6], we have decided to use chemical ligation with sugar containing synthons, based on  click chemistry (CC) protocols which involve alkyne – azide 1,3-dipolar cycloaddition reaction [5,7]. Triazoles obtained in such reactions feature characteristics, which are considered favorable from drug design point of view: chemical and metabolic stability, polarizability, hydrogen bond accepting properties, and predictable influence on logP and pK values. Protoescigenine diacetonide 28-O-propargyl ether, obtained by modified classical Williamson method was used as an alkyne component, while azides varied from substituted benzoic acid to mono and disaccharides, with azido substituent placed either in the pyranose ring or in an alkyl aglycone part. Various conditions for CC reaction were tested, including influence of Cu(I) and Cu(II) salts promotion. Obtained triazoles were purified by SiO2 column chromatography and characterized by standard spectroscopic methods.


Support from European and Regional Funds under project POIG.0101.02-14-072/09-00 grant  „Search of innovative endothelial drug in a group of new escin derivatives” Project  Leader: prof. dr hab. Katarzyna Koziak, Department of General and Nutritional Biochemistry, Warsaw Medical University, Żwirki i Wigury 61, Warszawa 02-091, Poland. Project site:

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[3]    Gruza, M.M.; Jatczak, K.; Zagrodzki, B.; Łaszcz, M.; Koziak, K.; Malińska, M.; Cmoch, P.; Giller, T.; Zegrocka-Stendel, O.; Woźniak, K.; Grynkiewicz, G. Molecules 2013, 18, 4389-4402.
[4]    Gruza, M.M.; Zegrocka-Stendel, O.; Giller, T.; Grynkiewicz, G.; Łaszcz, M.; Jatczak, K. PCT/PL2012/000102, 2012.10.12.
[5]    Meldal, M. ; Tornøe, C. W. Chem. Rev. 2008, 108, 2952–3015.

[6]    Gruza, M.M.; Jatczak, K.; Łaszcz, M.; Grynkiewicz, G.; Giller, T.; Witkowska, A. PL 402306, 2012.12.30.

[7]    Brotherton, W. S.; Michaels, H. A.; Simmons, J. T.; Clark, R. J.; Dalal, N. S.; Zhu, L. Org. Lett. 2009, 11, 4954–4957.


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Presentation: Poster at IX Multidyscyplinarna Konferencja Nauki o Leku, by Mariusz M. Gruza
See On-line Journal of IX Multidyscyplinarna Konferencja Nauki o Leku

Submitted: 2014-04-17 10:18
Revised:   2014-04-29 11:37