Glycoconjugate Journal

, Volume 30, Issue 8, pp 769–780 | Cite as

Synthesis of guanidino sugar conjugates as GlcβArg analogs



The β-glucosyl linkage to the guanidine group of arginine (Arg) is found in amylogenin, a glycoprotein from sweet corn. Such a linkage is formed by a rare N-glycosylation of proteins. Synthesis of analogs of the unusual N-glycosidic linkage (GlcβArg) with an acetamido or triazole spacer between the glycosyl residue and the guanidine moiety was accomplished by the reaction of fully acetylated sugar unit containing a free amino group with bis-Boc-thiourea. Synthesis of N-glucosylarginine with an amido linker was also achieved during the present study. This methodology was also extended to the synthesis of cationic glucolipid.


N-Glycoprotein Linkage region analogs Guanidine Arginine 



The funding provided by the Department of Science and Technology, New Delhi, for the purchase of a 400 MHz NMR under IRHPA scheme and ESI-MS under the FIST program is gratefully acknowledged. One of us (A.S.) is thankful to the Council of Scientific and Industrial Research (CSIR), New Delhi, for the award of a Senior Research Fellowship.

Supplementary material

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  1. 1.
    Ishikawa, T.: Superbases for Organic Synthesis. wiley (2009)Google Scholar
  2. 2.
    Berlinck, R.G.S., Burtoloso, A.C.B., Trindade-Silva, A.E., Romminger, S., Morais, R.P., Bandeira, K., Mizuno, C.M.: The chemistry and biology of organic guanidine derivatives. Nat. Prod. Rep. 27, 1871–1907 (2010)PubMedCrossRefGoogle Scholar
  3. 3.
    Cole, D.C., Manas, E.S., Stock, J.R., Condon, J.S., Jennings, L.D., Aulabaugh, A., Chopra, R., Cowling, R., Ellingboe, J.W., Fan, K.Y., Harrison, B.L., Hu, Y., Jacobsen, S., Jin, G., Lin, L., Lovering, F.E., Malamas, M.S., Stahl, M.L., Strand, J., Sukhdeo, M.N., Svenson, K., Turner, M.J., Wagner, E., Wu, J., Zhou, P., Bard, J.: Acylguanidines as small-molecule β-secretase inhibitors. J. Med. Chem. 49, 6158–6161 (2006)PubMedCrossRefGoogle Scholar
  4. 4.
    Zhang, R., Lei, L., Xu, Y., Hua, W., Gong, G.: Benzimidazol-2-yl or benzimidazol-2-ylthiomethylbenzoylguanidines as novel Na+/H+ exchanger inhibitors, synthesis and protection against ichemic reperfusion injury. Bioorg. Med. Chem. Lett. 17, 2430–2433 (2007)PubMedCrossRefGoogle Scholar
  5. 5.
    Banfi, L., Basso, A., Damonte, G., Pellegrini, F.D., Galatini, A., Guanti, G., Monfardini, I., Riva, R., Scapolla, C.: Synthesis and biological evaluation of new conformationally biased integrin ligands based on tetrahydroazoninone scaffold. Bioorg. Med. Chem. Lett. 17, 1341–1345 (2007)PubMedCrossRefGoogle Scholar
  6. 6.
    Chand, P., Bantia, S., Kotian, P.L., El-Kattan, Y., Lin, T., Babu, Y.S.: Comparison of the anti-influenza virus activity of cyclopentane derivatives with oseltamivir and zanamivir in vivo. Bioorg. Med. Chem. 13, 4071–4077 (2005)PubMedCrossRefGoogle Scholar
  7. 7.
    Rodriguez, F., Rozas, I., Kaiser, M., Brun, R., Nguyen, B., Wilson, W.D., García, R.N., Dardonville, C.: New bis(2-aminoimidazoline) and bisguanidine DNA minor groove binders with potent in vivo antitrypanosomal and antiplasmodial activity. J. Med. Chem. 51, 909–923 (2008)PubMedCrossRefGoogle Scholar
  8. 8.
    Delaware, D.L., Sharma, M.S., Iyengar, B.S., Remers, W.A.: Aminoglycoside antibiotics. 7. Dihydrostreptomycin analogues. J. Antibiot. 39, 251–258 (1986)PubMedCrossRefGoogle Scholar
  9. 9.
    Reitz, A.B., Tuman, R.W., Marchione, C.S., Jordan Jr., A.D., Bowden, C.R., Maryanoff, B.E.: Carbohydrate biguanides as potential hypoglycemic agents. J. Med. Chem. 32, 2110–2116 (1989)PubMedCrossRefGoogle Scholar
  10. 10.
    Merrer, Y.L., Gauzy, L., Gravier-Pelletier, C., Depezay, J.C.: Synthesis of C2-symmetric guanidino-sugars as potent inhibitors of glycosidases. Bioorg. Med. Chem. 8, 307–320 (2000)PubMedCrossRefGoogle Scholar
  11. 11.
    Aguilar, M., Díaz-Pérez, P., García-Moreno, M.I., Mellet, C.O., García Fernández, J.M.: Synthesis and biological evaluation of guanidine-type iminosugars. J. Org. Chem. 73, 1995–1998 (2008)PubMedCrossRefGoogle Scholar
  12. 12.
    Gravier-Pelletier, C., Bourissou, D., Merrer, Y.L., Depezay, J.C.: Nucleophilic opening of epoxide by guanidine. A route to potential substrates or inhibitors of NO synthases. Synlett 275–277 (1996)Google Scholar
  13. 13.
    Singh, D.G., Lomako, J., Lomako, W.M., Whelan, W.J., Meyer, H.E., Serwe, M., Metzger, J.W.: β-Glucosylarginine: a new glucose-protein bond in a self-glucosylating protein from sweet corn. FEBS Lett. 376, 61–64 (1995)Google Scholar
  14. 14.
    Spiro, R.G.: Protein glycosylation: nature, distribution, enzymatic formation, and disease implications of glycopeptide bonds. Glycobiology 12, 43R–56R (2002)PubMedCrossRefGoogle Scholar
  15. 15.
    Kazuyuki, M., Kyoko, I.: l-(Nα-L-Arginino)-1-deoxy-β-D-fructose and 1-(Nα-L-arginino)1-deoxy-β-D-glucose. Nippon Kagaku Zasshi 80, 565–569 (1959)CrossRefGoogle Scholar
  16. 16.
    Micheel, F., Heesing, A.: The stability of the N-glycosides, particularly guanidine glycoside and nucleosides. Chem. Ber. 94, 1814–1824 (1961)CrossRefGoogle Scholar
  17. 17.
    Micheel, F., Heesing, A.: Synthesis of D-glucosylguanylamino acids and proteins. Justus Liebigs Ann. Chem. 604, 34–41 (1957)CrossRefGoogle Scholar
  18. 18.
    Micheel, F., Habendorff, R.: D-Glucuronyl derivatives of amino acids and proteins. Chem. Ber. 90, 1590–1595 (1957)CrossRefGoogle Scholar
  19. 19.
    Westphal, G., Kroh, L.: Studies on the Maillard reaction. Part I. Structure and reactivity of glucosylthiourea. Nahrung 25, 311–319 (1981)CrossRefGoogle Scholar
  20. 20.
    Kannan, T., Vinodhkumar, S., Varghese, B., Loganathan, D.: Synthesis of glycosyl phosphoramidates: novel isosteric analogs of glycosyl phosphates. Bioorg. Med. Chem. Lett. 11, 2433–2435 (2001)PubMedCrossRefGoogle Scholar
  21. 21.
    Chrysina, E.D., Kosmopoulou, M.N., Kardakaris, R., Bischler, N., Leonidas, D.D., Kannan, T., Loganathan, D., Oikonomakos, N.G.: Binding of β-D-glucopyranosyl bismethoxyphosphoramidate to glycogen phosphorylase b: Kinetic and crystallographic studies. Bioorg. Med. Chem. 13, 765–772 (2005)PubMedCrossRefGoogle Scholar
  22. 22.
    Petsalakis, E.I., Chrysina, E.D., Tiraidis, C., Hadjiloi, T., Oikonomakos, N.G., Aich, U., Varghese, B., Loganathan, D.: Crystallographic studies on N-azidoacetyl-β-D-glucopyranosylamine, an inhibitor of glycogen phosphorylase: comparison with N-acetyl-β-D-glucopyranosylamine. Bioorg. Med. Chem. 14, 5316–5324 (2006)PubMedCrossRefGoogle Scholar
  23. 23.
    Alexacou, K.M., Hayes, J.M., Tiraidis, C., Zographos, S.E., Leoni-das, D.D., Chrysina, E.D., Archontis, G., Oikonomakos, N.G., Paul, J.V., Varghese, B., Loganathan, D.: Crystallographic and computational studies on 4-phenyl-N-(β-D-glucopyranosyl)-1H-1,2,3-triazole-1-acetamide, an inhibitor of glycogen phosphorylase: comparison with α-D-glucose, N-acetyl-β-D-glucopyranosylamine and N-benzoyl-N′-β-D-glucopyranosyl urea binding. Proteins: Struct. Funct. Bioinf. 71, 1307–1323 (2008)CrossRefGoogle Scholar
  24. 24.
    Chrysina, E.D., Bokor, É., Alexacou, K.M., Charavgi, M.D., Oikonomakos, G.N., Zographos, S.E., Leonidas, D.D., Oikonomakos, N.G., Somsák, L.: Amide-1,2,3-triazole bioisosterism: the glycogen phosphorylase case. Tetrahedron-Asymmetry 20, 733–740 (2009)CrossRefGoogle Scholar
  25. 25.
    Bokor, É., Docsa, T., Gergely, P., Somsák, L.: Synthesis of 1-(D-glucopyranosyl)-1,2,3-triazoles and their evaluation as glycogen phosphorylase inhibitors. Bioorg. Med. Chem. 18, 1171–1180 (2010)PubMedCrossRefGoogle Scholar
  26. 26.
    Goyard, D., Baron, M., Skourti, P.V., Chajistamatiou, A.S., Docsa, T., Gergely, P., Chrysina, E.D., Praly, J.P., Vidal, S.: Synthesis of 1,2,3-triazoles from xylosyl and 5-thioxylosyl azides: evaluation of the xylose scaffold for the design of potential glycogen phosphorylase inhibitors. Carbohydr. Res. 364, 28–40 (2012)PubMedCrossRefGoogle Scholar
  27. 27.
    Katritzky, A.R., Rogovoy, B.V.: Recent developments in guanylating agents. ARKIVOC iv, 49–87 (2005)CrossRefGoogle Scholar
  28. 28.
    Expósito, A., Fernández-Suárez, M., Iglesias, T., Muňoz, L., Riguera, R.: Total synthesis and absolute configuration of minalemine A, a guanidine peptide from the marine tunicate Didemnum rodriguesi. J. Org. Chem. 66, 4206–4213 (2001)PubMedCrossRefGoogle Scholar
  29. 29.
    Paul, K.J.V., Sahoo, L., Sorna, V., Loganathan, D.: An improved procedure for the synthesis of fully acetylated N-(β-glycosyl)azidoacetamides and N-(β-glycosyl)iodoacetamides useful as chemical ligating agents. Trends Carbohydr. Res. 2, 21–28 (2010)Google Scholar
  30. 30.
    Wilkinson, B.L., Bornaghi, L.F., Poulsen, S., Houston, T.A.: Synthetic utility of glycosyl triazoles in carbohydrate chemistry. Tetrahedron 62, 8115–8125 (2006)CrossRefGoogle Scholar
  31. 31.
    Marra, A., Vecchi, A., Chiappe, C., Melai, B., Dondoni, A.: Validation of the copper (I)-catalyzed azide-alkyne coupling in ionic liquids. Synthesis of a triazole linked C-disaccharide as a case study. J. Org. Chem. 73, 2458–2461 (2008)PubMedCrossRefGoogle Scholar
  32. 32.
    Chen, X., Wang, J., Sun, S., Fan, J., Liu, S.J., Ma, S., Zhang, L., Peng, X.: Efficient enhancement of DNA cleavage activity by introducing guanidinium groups into diiron (III) complex. Bioorg. Med. Chem. Lett. 18, 109–113 (2008)PubMedCrossRefGoogle Scholar
  33. 33.
    Easmona, J., Heinischa, G., Holzer, W., Matuszczak, B.: Preparation of amino- and carboxy-protected L-α-amino-ω-iodocarboxylic acids. Arch. Pharm. (Weinheim) 328 367–370 (1995)Google Scholar
  34. 34.
    Mukthavaram, R., Marepally, S., Venkata, M.Y., Vegi, G.N., Sistla, R., Chaudhuri, A.: Cationic glycolipids with cyclic and open galactose head groups for the selective targeting of genes to mouse liver. Biomaterials 30, 2369–2384 (2009)PubMedCrossRefGoogle Scholar
  35. 35.
    Kumar, R., Maulik, P.R., Misra, A.K.: Significant rate accelerated synthesis of glycosyl azides and glycosyl 1,2,3-triazole conjugates. Glycoconj. J. 25, 595–602 (2008)PubMedCrossRefGoogle Scholar
  36. 36.
    Ortega-Muñoz, M., Perez-Balderas, F., Morales-Sanfrutos, J., Hernandez-Mateo, F., Isac-García, J., Santoyo-Gonzalez, F.: Click multivalent heterogeneous neoglycoconjugates–Modular synthesis and evaluation of their binding affinities. Eur. J. Org. Chem. 15, 2454–2473 (2009)CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  1. 1.Department of ChemistryIndian Institute of Technology MadrasChennaiIndia

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