, Volume 25, Issue 5, pp 2849–2859 | Cite as

Diversity of polysaccharide structures designed by aqueous Ugi-multi-compound reaction

  • Lars Gabriel
  • Thomas Heinze
Original Paper


Carboxymethyl ethers of xylan, cellulose, and pullulan could be efficiently modified applying the Ugi-reaction in the “green” solvent water. Using different components, namely an aldehyde, an amine, and an isonitrile, the reaction led to novel polysaccharide derivatives with peptide-like substituents. The reactions were carried out applying 2-methoxyethylamine and propargyl amine, paraformaldehyde and benzaldehyde as well as tert-butylisonitrile at room temperature. The characterization of the products was performed by 13C-NMR spectroscopy. In any case, a high conversion of the carboxyl groups could be realized. The products isolated possessed a lower degree of substitution compared to the starting material, which may result from a hydrolytic cleavage of ether bonds. Nevertheless, the results indicated that carboxymethylated polysaccharides are useful starting materials for new polysaccharide derivatives in a toolbox reaction.

Graphical Abstract


Ugi-reaction Polysaccharides Multicomponent reaction Carboxymethyl cellulose Carboxymethyl xylan Carboxymethyl pullulan 

Supplementary material

10570_2018_1754_MOESM1_ESM.docx (259 kb)
Supplementary material 1 (DOCX 259 kb)


  1. Arcelli A, Porzi G, Rinaldi S, Sandri S (2001) An efficient acid hydrolysis of the ether bond assisted by the neighbouring benzamide group. Part 3. J Chem Soc Perkin Trans 2:296–301. CrossRefGoogle Scholar
  2. Arcelli A, Porzi G, Rinaldi S, Sandri S (2004) Effect of neighbouring amide group bulkiness on anchimerically assisted ether bond cleavage: Part 7. J Phys Org Chem 17:289–293. CrossRefGoogle Scholar
  3. Brauch S, Gabriel L, Westermann B (2010) Seven-component reactions by sequential chemoselective Ugi–Mumm/Ugi–Smiles reactions. Chem Commun 46:3387–3389. CrossRefGoogle Scholar
  4. Bu H, Kjøniksen A-L, Nyström B (2005) Effects of pH on dynamics and rheology during association and gelation via the Ugi reaction of aqueous alginate. Eur Polym J 41:1708–1717. CrossRefGoogle Scholar
  5. Calvaresi M, Rinaldi S, Arcelli A, Garavelli M (2008) Computational DFT investigation of vicinal amide group anchimeric assistance in ether cleavage. J Org Chem 73:2066–2073. CrossRefGoogle Scholar
  6. Camacho C, Matías JC, García D, Simpson BK, Villalonga R (2007) Amperometric enzyme biosensor for hydrogen peroxide via Ugi multicomponent reaction. Electrochem Commun 9:1655–1660. CrossRefGoogle Scholar
  7. Daus S, Petzold-Welcke K, Kötteritzsch M, Baumgaertel A, Schubert US, Heinze T (2011) Homogeneous sulfation of xylan from different sources. Macromol Mater Eng 296:551–561. CrossRefGoogle Scholar
  8. de Nooy AE, Masci G, Crescenzi V (1999) Versatile synthesis of polysaccharide hydrogels using the Passerini and Ugi multicomponent condensations. Macromolecules 32:1318–1320. CrossRefGoogle Scholar
  9. de Nooy AEJ, Capitani D, Masci G, Crescenzi V (2000) Ionic polysaccharide hydrogels via the Passerini and Ugi multicomponent condensations: synthesis, behavior and solid-state NMR characterization. Biomacromolecules 1:259–267. CrossRefGoogle Scholar
  10. Demleitner S, Kraus J, Franz G (1992) Synthesis and antitumour activity of sulfoalkyl derivates of curdlan and lichenan. Carbohydr Res 226:247–252. CrossRefGoogle Scholar
  11. Dömling A (2006) Recent developments in isocyanide based multicomponent reactions in applied chemistry. Chem Rev 106:17–89. CrossRefGoogle Scholar
  12. Dömling A, Ugi I (2000) Multicomponent Reactions with Isocyanides. Angew Chem Int Ed 39:3168–3210.<3168:aid-anie3168>;2-u CrossRefGoogle Scholar
  13. Ebringerová A, Pastýr J (1988) Sulfoethylierung von D-Xylanen in heterogener Phase. Chem Pap 3:407–414Google Scholar
  14. Elschner T, Heinze T (2015) Cellulose carbonates: A platform for promising biopolymer derivatives with multifunctional capabilities. Macromol Biosci 15:735–746CrossRefGoogle Scholar
  15. Elschner T, Ganske K, Heinze T (2013a) Synthesis and aminolysis of polysaccharide carbonates. Cellulose 20:339–353. CrossRefGoogle Scholar
  16. Elschner T, Wondraczek H, Heinze T (2013b) Syntheses and detailed structure characterization of dextran carbonates. Carbohydr Polym 93:216–223CrossRefGoogle Scholar
  17. Freeman A, Sokolovsky M, Goldstein L (1979) Isonitrile derivatives of polysaccharides as supports for the covalent fixation of proteins and other ligands. Biochim Biophys Acta Enzymol 571:127–136. CrossRefGoogle Scholar
  18. García A, Hernández K, Chico B, García D, Villalonga ML, Villalonga R (2009) Preparation of thermostable trypsin–polysaccharide neoglycoenzymes through Ugi multicomponent reaction. J Mol Catal B Enzym 59:126–130. CrossRefGoogle Scholar
  19. Gericke M, Liebert T, Heinze T (2009) Interaction of ionic liquids with polysaccharides, 8—synthesis of cellulose sulfates suitable for polyelectrolyte complex formation. Macromol Biosci 9:343–353. CrossRefGoogle Scholar
  20. Hammaker RM, Gugler BA (1965) An NMR study of hindered internal rotation in N,N-dialkyl amides. J Mol Spectrosc 17:356–364. CrossRefGoogle Scholar
  21. Heinze T (1998) Ionische Funktionspolymere aus Cellulose: Neue Synthesekonzepte, Strukturaufklärung und Eigenschaften. Shaker Verlag, AachenGoogle Scholar
  22. Heinze T, Pfeiffer K (1999) Studies on the synthesis and characterisation of carboxymethylcellulose. Angew Macromol Chem 266:37–45CrossRefGoogle Scholar
  23. Heinze T, Rahn K (1997) Cellulose-p-toluenesulfonates: a valuable intermediate in cellulose chemistry. In: Macromolecular symposia, vol 1. Wiley Online Library, pp 103–113.
  24. Heinze U, Heinze T, Klemm D (1999) Synthesis and structure characterization of 2,3-O-carboxymethylcellulose. Macrmol Chem Phys 200:896–902CrossRefGoogle Scholar
  25. Heinze T, Koschella A, Brackhagen M, Engelhardt J, Nachtkamp K (2006a) Studies on non-natural deoxyammonium cellulose. In: Macromolecular symposia, vol 1. Wiley Online Library, pp 74–82.
  26. Heinze T, Liebert T, Koschella A (2006b) Esterification of polysaccharides. Springer, Heidelberg. Google Scholar
  27. Herrero LJ, Foo S-S, Sheng K-C, Chen W, Forwood MR, Bucala R, Mahalingam S (2015) Pentosan polysulfate: A novel glycosaminoglycan-like molecule for effective treatment of alphavirus-induced cartilage destruction and inflammatory disease. J Virol 89:8063–8076. CrossRefGoogle Scholar
  28. Hornig S, Bunjes H, Heinze T (2009) Preparation and characterization of nanoparticles based on dextran–drug conjugates. J Colloid Interface Sci 338:56–62. CrossRefGoogle Scholar
  29. Konduri MK, Fatehi P (2016) Synthesis and characterization of carboxymethylated xylan and its application as a dispersant. Carbohydr Polym 146:26–35. CrossRefGoogle Scholar
  30. Koschella A, Heinze T (2001) Novel regioselectively 6-functionalized cationic cellulose polyelectrolytes prepared via cellulose sulfonates. Macromol Biosci 1:178–184.<178:AID-MABI178>3.0.CO;2-E CrossRefGoogle Scholar
  31. Mironov MA, Shulepov ID, Ponomarev VS, Bakulev VA (2013) Synthesis of polyampholyte microgels from colloidal salts of pectinic acid and their application as pH-responsive emulsifiers. Colloid Polym Sci 291:1683–1691. CrossRefGoogle Scholar
  32. Petzold K, Schwikal K, Günther W, Heinze T (2006a) Carboxymethyl xylan—control of properties by synthesis. Macromol Symp 232:27–36. CrossRefGoogle Scholar
  33. Petzold K, Schwikal K, Heinze T (2006b) Carboxymethyl xylan—synthesis and detailed structure characterization. Carbohydr Polym 64:292–298CrossRefGoogle Scholar
  34. Rahn K, Diamantoglou M, Klemm D, Berghmans H, Heinze T (1996) Homogeneous synthesis of cellulose p-toluenesulfonates in N,N-dimethylacetamide/LiCl solvent system. Macromol Mater Eng 238:143–163. Google Scholar
  35. Rivera DG, Pérez-Labrada K, Lambert L, Dörner S, Westermann B, Wessjohann LA (2012) Carbohydrate–steroid conjugation by Ugi reaction: one-pot synthesis of triple sugar/pseudo-peptide/spirostane hybrids. Carbohydr Res 359:102–110. CrossRefGoogle Scholar
  36. Schulze P, Gericke M, Scholz F, Wondraczek H, Miethe P, Heinze T (2016) Incorporation of hydrophobic dyes within cellulose acetate and acetate phthalate based nanoparticles. Macrmol Chem Phys 217:1823–1833. CrossRefGoogle Scholar
  37. Shulepov ID, Kozhikhova KV, Panfilova YS, Ivantsova MN, Mironov MA (2016) One-pot synthesis of cross-linked sub-micron microgels from pure cellulose via the Ugi reaction and their application as emulsifiers. Cellulose 23:2549–2559. CrossRefGoogle Scholar
  38. Sibikina OV, Iozep AA, Passet BV (2004a) Acylation of aromatic amines with carboxymethyl dextran in the presence of small amounts of water. Russ J Appl Chem 77:1147–1149. CrossRefGoogle Scholar
  39. Sibikina OV, Iozep AA, Passet BV (2004b) Reactions of carboxymethyl polysaccharides and their ethyl esters with amines. Russ J Appl Chem 77:263–266. CrossRefGoogle Scholar
  40. Tezuka Y, Tsuchiya Y, Shiomi T (1996) 13C NMR determination of substituent distribution in carboxymethylcellulose by use of its peresterified derivatives. Carbohydr Res 291:99–108. CrossRefGoogle Scholar
  41. Tiitu M, Laine J, Serimaa R, Ikkala O (2006) Ionically self-assembled carboxymethyl cellulose/surfactant complexes for antistatic paper coatings. J Coll Inter Sci 301:92–97. CrossRefGoogle Scholar
  42. Vieira MC, Klemm D, Einfeldt L, Albrecht G (2005) Dispersing agents for cement based on modified polysaccharides. Cem Concr Res 35:883–890. CrossRefGoogle Scholar
  43. Werner B, Bu H, Kjøniksen A-L, Sande SA, Nyström B (2006) Characterization of gelation of aqueous pectin via the Ugi multicomponent condensation reaction. Polym Bull 56:579–589. CrossRefGoogle Scholar
  44. Wu Q-X, Wang D-D, Su T, Cheng X-D, Xu X, Chen Y (2017) Self-assembly of polyelectrolyte complexes microcapsules with natural polysaccharides for sustained drug release. Cellulose 24:4949–4962. CrossRefGoogle Scholar
  45. Zhang K, Brendler E, Gebauer K, Gruner M, Fischer S (2011) Synthesis and characterization of low sulfoethylated cellulose. Carbohydr Polym 83:616–622. CrossRefGoogle Scholar
  46. Zieger M et al (2015) 6-Deoxy-6-aminoethyleneamino cellulose: synthesis and study of hemocompatibility. J Biomater Sci Polym Ed 26:931–946. CrossRefGoogle Scholar
  47. Ziyaei Halimehjani A, Sharifi M (2017) Synthesis of a novel category of Ugi adducts using succinic acid, succinic anhydride and maleic anhydride and their application in post-Ugi reactions for synthesis of functionalized piperazine 2,5-diones. Tetrahedron 73:5778–5783. CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media B.V., part of Springer Nature 2018

Authors and Affiliations

  1. 1.Institute of Organic Chemistry and Macromolecular Chemistry, Centre of Excellence for Polysaccharide ResearchFriedrich Schiller University of JenaJenaGermany

Personalised recommendations