Straightforward synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O43 strain


A concise synthetic strategy has been developed for the synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O43 strain involving stereoselective β-D-mannosylation and α-L-fucosylation using corresponding trichloroacetimidate intermediates and perchloric acid supported over silica (HClO4-SiO2) as glycosylation promoter. The yield and stereoselectivity of the glycosylations were very good.

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  1. 1.

    Mokomane, M., Kasvosve, I., de Melo, E., Pernica, J.M., Goldfarb, D.M.: The global problem of childhood diarrhoeal diseases: emerging strategies in prevention and management. Ther. Adv. Infect, Dis. 5, 29–43 (2018)

    Google Scholar 

  2. 2.

    Ashbolt, N.J.: Microbial contamination of drinking water and disease outcomes in developing regions. Toxicology. 198, 229–238 (2004)

    CAS  Article  Google Scholar 

  3. 3.

    Dekker, J., Frank, K.: Salmonella, Shigella, and Yersinia. Clin. Lab. Med. 35, 225–246 (2015)

    Article  Google Scholar 

  4. 4.

    Crump, J.A., Sjölund-Karlsson, M., Gordon, M.A., Parry, C.M.: Epidemiology, clinical presentation, laboratory diagnosis, antimicrobial resistance, and antimicrobial management of invasive Salmonella Infections. Clin. Microbiol. Rev. 28, 901–937 (2015)

    CAS  Article  Google Scholar 

  5. 5.

    Morris Jr., J.G., Acheson, D.: Cholera and other types of vibriosis: a story of human pandemics and oysters on the half Shell. Clin. Infect. Dis. 37, 272–280 (2003)

    Article  Google Scholar 

  6. 6.

    Clements, A., Young, J.C., Constantinou, N., Frankel, G.: Infection strategies of enteric pathogenic Escherichia coli. Gut Microbes. 3, 71–87 (2012)

    Article  Google Scholar 

  7. 7.

    Acheson, D., Allos, B.M.: Campylobacter jejuni infections: update on emerging issues and trends. Clin. Infect. Dis. 32, 1201–1206 (2001)

    Article  Google Scholar 

  8. 8.

    Orskov, I., Orskov, F., Jann, B., Jann, K.: Serology, chemistry, and genetics of O and K antigens of Escherichia coli. Bacterial Rev. 41, 667–710 (1977)

    CAS  Article  Google Scholar 

  9. 9.

    Kaper, J.B., Nataro, J.P., Mobley, H.L.T.: Pathogenic Escherichia coli. Nat. Rev. Microbiol. 2, 123–140 (2004)

    CAS  Article  Google Scholar 

  10. 10.

    Johnson, J.R., Russo, T.A.: Extraintestinal pathogenic Escherichia coli : “the other bad E coli ”. J. Lab. Clin. Med. 139, 155–162 (2002)

    CAS  Article  Google Scholar 

  11. 11.

    Kelly, P.: Infectious diarrhoea. Medicine. 39, 201–206 (2011)

    Article  Google Scholar 

  12. 12.

    Stenutz, R., Weintraub, A., Widmalm, G.: The structures of Escherichia coli O-polysaccharide antigens. FEMS Microbiol. Rev. 30, 382–403 (2006)

    CAS  Article  Google Scholar 

  13. 13.

    Paton, J.C., Paton, A.W.: Pathogenesis and diagnosis of Shiga toxin-producing Escherichia coli infections. Clin. Microbiol. Rev. 11, 450–479 (1998)

    CAS  Article  Google Scholar 

  14. 14.

    Nataro, J.P., Kaper, J.B.: Diarrheagenic Escherichia coli. Clin. Microbiol. Rev. 11, 142–201 (1998)

    CAS  Article  Google Scholar 

  15. 15.

    Perepelov, A.V., Guo, X., Filatov, A.V., Liu, B., Knirel, Y.A.: Structure and gene cluster of the O-antigen of Escherichia coli O43. Carbohydr. Res. 416, 32–36 (2015)

    CAS  Article  Google Scholar 

  16. 16.

    Roy, R.: New trends in carbohydrate based vaccines. Drug Discov. Today Technol. 1, 327–336 (2004)

    CAS  Article  Google Scholar 

  17. 17.

    Hölemann, A., Seeberger, P.H.: Carbohydrate diversity: synthesis of glycoconjugates and complex carbohydrates. Curr. Opin. Biotechnol. 15, 615–622 (2004)

    Article  Google Scholar 

  18. 18.

    Pozsgay, V.: Recent developments in synthetic oligosaccharide-based bacterial vaccines. Curr. Top. Med. Chem. 8, 126–140 (2008)

    CAS  Article  Google Scholar 

  19. 19.

    Morelli, L., Poletti, L., Lay, L.: Carbohydrates and immunology: synthetic oligosaccharide antigens for vaccine formulation. Eur. J. Org. Chem. 5723–5777 (2011)

  20. 20.

    Lee, C.-J., Lee, L.H., Frasch, C.E.: Protective immunity of pneumococcal glycoconjugates. Crit. Rev. Microbiol. 29, 333–349 (2003)

    CAS  Article  Google Scholar 

  21. 21.

    Cheesman, M.J., Ilanko, A., Blonk, B., Cock, I.E.: Developing new antimicrobial therapies: are synergistic combinations of plant extracts/compounds with conventional antibiotics the solution? Pharmacogn. Rev. 11, 57–72 (2017)

    CAS  Article  Google Scholar 

  22. 22.

    He, H., Chen, D., Li, C., Zhao, J.-H., Qin, H.-B.: Synthesis of trisaccharide repeating unit of fucosylated chondroitin sulfate. Org. Biomol. Chem. 17, 2877–2882 (2019)

    CAS  Article  Google Scholar 

  23. 23.

    Susanto, W., Kong, K.-H., Hua, K.-F., Wu, S.-H., Lam, Y.: Synthesis of the trisaccharide repeating unit of capsular polysaccharide from Klebsiella pneumonia. Tetrahedron Lett. 60, 288–291 (2019)

    CAS  Article  Google Scholar 

  24. 24.

    Gucchait, Misra, A.K.: Influence of remote functional groups towards the formation of 1,2-cis glycosides: special emphasis on β-mannosylation. Org. Biomol. Chem. 17, 4605–4610 (2019)

    CAS  Article  Google Scholar 

  25. 25.

    Lönn, H.: Synthesis of a tri- and a heptasaccharide which contain α-L-fucopyranosyl groups and are part of the complex type of carbohydrate moiety of glycoproteins. Carbohydr. Res. 139, 105–113 (1985)

    PubMed  Google Scholar 

  26. 26.

    Schmidt, R.R., Zhu, X.: Glycosyl Trichloroacetimidates. In: Fraser-Reid, B.O., Tatsuta, K., Thiem, J. (eds.) Glycoscience. Springer, Berlin, Heidelberg (2008).

    Google Scholar 

  27. 27.

    Chakraborti, A.K., Gulhane, R.: Perchloric acid adsorbed on silica gel as a new, highly efficient, and versatile catalyst for acetylation of phenols, thiols, alcohols, and amines. Chem. Commun. 2003, (1896-1897)

  28. 28.

    Mukhopadhyay, B., Maurer, S.V., Rudolph, N., van Well, R.M., Russell, D.A., Field, R.A.: From solution phase to “on-column” chemistry: trichloroacetimidate-based glycosylation promoted by perchloric acid-silica. J. Org. Chem. 70, 9059–9062 (2005)

    CAS  Article  Google Scholar 

  29. 29.

    Si, A., Misra, A.K.: Synthesis of a pentasaccharide repeating unit corresponding to the cell wall O-antigen of Escherichia coli O59 using iterative glycosylations in one pot. Tetrahedron. 72, 4435–4441 (2016)

    CAS  Article  Google Scholar 

  30. 30.

    Love, K.R., Andrade, R.B., Seeberger, P.H.: Linear synthesis of a protected H-type II pentasaccharide using glycosyl phosphate building blocks. J. Org. Chem. 66, 8165–8176 (2001)

    CAS  Article  Google Scholar 

  31. 31.

    DeNinno, M.P., Etienne, J.B., Duplantier, K.C.: A method for the selective reduction of carbohydrate 4,6-O-benzylidene acetals. Tetrahedron Lett. 36, 669–672 (1995)

    CAS  Article  Google Scholar 

  32. 32.

    Ishiwata, A., Munemura, Y., Ito, Y.: Synergistic solvent effect in 1,2-cis-glycoside formation. Tetrahedron. 64, 92–102 (2008)

    CAS  Article  Google Scholar 

  33. 33.

    Kanie, O., Ito, Y., Ogawa, T.: Orthogonal glycosylation strategy in oligosaccharide synthesis. J. Am. Chem. Soc. 116, 12073–12074 (1994)

    CAS  Article  Google Scholar 

  34. 34.

    Kasai, R., Okihara, M., Asakawa, J., Mizutani, K., Tanaka, O.: 13C NMR study of α- and β-anomeric pairs of D-mannopyranosides and L-rhamnopyranosides. Tetrahedron Lett. 35, 1427–1432 (1979)

    CAS  Article  Google Scholar 

  35. 35.

    Bock, K., Pedersen, C.: A study of 13CH coupling constants in hexopyranoses. J. Chem. Soc. Perkin Trans. 2, 293–297 (1974)

    Article  Google Scholar 

  36. 36.

    Wuts, P.G.M.: In: Crich, D. (ed.) Handbook of Reagents for Organic Synthesis: Reagents for Glycoside, Nucleotide, and Peptide Synthesis, pp. 425–428. Wiley, Chichester (2005)

    Google Scholar 

  37. 37.

    Mukherjee, C., Misra, A.K.: Glycosylation and pyranose-furanose isomerization of carbohydrates using HClO4-SiO2: synthesis of oligosaccharides containing galactofuranose. Synthesis. 683–692 (2007)

  38. 38.

    Fügedi, P., Garegg, P.J.: A novel promoter for the efficient construction of 1,2-trans linkages in glycoside synthesis, using thioglycosides as glycosyl donors. Carbohydr. Res. 149, C9–C-12 (1986)

    Article  Google Scholar 

  39. 39.

    Veeneman, G.H., van Leeuwen, S.H., van Boom, J.H.: Iodonium ion promoted reactions at the anomeric centre. II An efficient thioglycoside mediated approach toward the formation of 1,2-trans linked glycosides and glycosidic esters. Tetrahedron Lett. 31, 1331–1334 (1990)

    CAS  Article  Google Scholar 

  40. 40.

    Lönn, H.: Glycosylation using a thioglycoside and methyl trifluoromethanesulfonate. A new and efficient method for cis and trans glycoside formation. J. Carbohydr. Chem. 6, 301–306 (1986)

    Article  Google Scholar 

  41. 41.

    Zheng, X., Xu, D., Edgar, K.J.: Cellulose levulinate: a protecting group for cellulose that can be selectively removed in the presence of other ester groups. Cellulose. 22, 301–311 (2015)

    CAS  Article  Google Scholar 

  42. 42.

    Bhattacharyya, S., Magnusson, B.G., Wellmar, U., Nilsson, U.J.: The p-methoxybenzyl ether as an in situ-removable carbohydrate-protecting group: a simple one-pot synthesis of the globotetraose tetrasaccharide. J. Chem. Soc. Perkin Trans. 1, 886–890 (2001)

    Article  Google Scholar 

  43. 43.

    Shangguan, N., Katukojvala, S., Greenberg, R., Williams, L.J.: The reaction of thio acids with azides: a new mechanism and new synthetic applications. J. Am. Chem. Soc. 125, 7754–7755 (2003)

    CAS  Article  Google Scholar 

  44. 44.

    Pearlman, W.M.: Noble metal hydroxides on carbon nonpyrophoric dry catalysts. Tetrahedron Lett. 8, 1663–1664 (1967)

    Article  Google Scholar 

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P. S. thanks CSIR, New Delhi for providing Senior Research Fellowship. The work is supported by SERB, India (Project No. CRG/2019/000352 dated 23.01.2020) (AKM) and Bose Institute.

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Correspondence to Anup Kumar Misra.

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Shit, P., Misra, A.K. Straightforward synthesis of the pentasaccharide repeating unit of the cell wall O-antigen of Escherichia coli O43 strain. Glycoconj J (2020).

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  • Oligosaccharide
  • Glycosylation
  • O-antigen
  • Diarrhea
  • E. coli