Advertisement

Combinatorial Carbohydrate Chemistry

  • Zhi-Guang Wang
  • Ole Hindsgaul
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 435)

Abstract

Modern organic/medicinal chemistry is undergoing a “cultural revolution” in the way new drugs are discovered and developed. Instead of discrete synthess and biological screening of individual compounds, which often takes years to identify and optimize leads, the currently developing technology called “combinatorial chemistry” can rapidly provide large numbers of chemicals (libraries) in a short time. In conjunction with these new synthetic methods, high-throughput screening (HTS) can rapidly screen the libraries produced, and in so doing, can provide information for optimizing lead compounds. This is going to lighten the increasing burden traditional drug development places on the pharmaceutical industry. For this reason, the generation of chemical libraries through combinatorial chemistry, including parallel synthesis, is making explosive progress both in academic and industrial areas in the last two years, especially for creating peptide, nucleotide and small molecule libraries. A number of excellent reviews1 on this field have appeared.

Keywords

Insoluble Polymer Library Synthesis Oligosaccharide Synthesis Small Molecule Library Merrifield Resin 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.(a)
    M.A. Gallop, R.W. Barrett, W.J. Dower, S.P.A. Fodor, and E.M. Gordon, Application of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries, J. Med. Chem. 37:1233 (1994). 2. Combinatorial organic synthesis, library screening strategies and future directions, 37:1385 (1994).PubMedCrossRefGoogle Scholar
  2. 1.(b)
    L.A. Thompson and J.A. Ellman. Synthesis ands applications of small molecular libraries. Chem. Rev. 96:555(1996).PubMedCrossRefGoogle Scholar
  3. 1.(c)
    P.H.H. Hermkens, H.C.J. Ottenheijm, and D. Rees, Solid phase organic reactions: a review of the recent literature, Tetrahedron 52:4527 (1996)CrossRefGoogle Scholar
  4. 1.(d)
    F. Balkenhohl, C. Bussche-Hunnefeld, A. Lansky, and C. Zechel, Combinatorial synthesis of small organic molecules, Angew. Chem. Int. Ed. Engl. 35:2288 (1996).CrossRefGoogle Scholar
  5. 2.
    A recent general review about glycosylation: K. Toshima, and K. Tatsuta, Recent progress in O-glycosylation methods and its application to natural products synthesis, Chem. Rev. 93:1503 (1993).CrossRefGoogle Scholar
  6. 3.
    See a recent review: J.C. Mc Auliffe, and O. Hindsgaul, Carbohydrate drugs—an ongoing challenge, Chemistry and Industry 170 (1997).Google Scholar
  7. 4.(a)
    O. Kanie, F. Bafresi, Y. Ding, J. Labbe, A. Otter, L. S. Forsberg, B. Ernst, and O. Hindsgaul. A strategy of “random glycosylation” for the production of oligosaccharide libraries, Angew. Chem. Int. Ed. Engl. 34:2720 (1995).CrossRefGoogle Scholar
  8. 4.(b)
    Y. Ding, J. Labbe, O. Kanie, and O. Hindsgaul, Towards oligosaccharide libraries: a study of the random galactosylation of unprotected N-acetylglucosamine, Bioorg. Biomed. Chem. 4:683 (1996).Google Scholar
  9. 5.
    G.J. Boons, B. Heskamp, and F. Hout, Vinyl glycosides in oligosaccharide synthesis: a strategy for the preparation of trisaccharide libraries based on latent-active glycosylation, Angew. Chem. Int. Ed, Engl. 35:2845 (1996).CrossRefGoogle Scholar
  10. 6.(a)
    Z.G. Wang, S. Douglas and J.J. Krepinsky, Polymer-supported synthesis of oligosaccharides: using dibutylboron triflate to promote glycosylation with glycosyl trichloro-acetimidates, Tetrahedron Lett. 37:6985 (1996).CrossRefGoogle Scholar
  11. 6.(b)
    J.J. Krepinsky, 212th Amercian Chemical Society National Meeting at Orlando, August 25–29, Division of Organic Chemistry, 003 (1996). Previous works on soluble-phase polymer-supported synthesis See: S. Douglas, D.M. Whitfiled, and J.J. Krepinsky, Polymer-supported synthesis of oligosaccharides using a novel versatile linker for the synthesis of D-mannopentaose, a structural unit of D-Mannans of pathogenic yeasts, J. Am. Chem. Soc. 117:2116 (1995).Google Scholar
  12. 7.
    R. Liang, L. Yan, J. Loebach, M. Ge, Y. Uozumi, K. Sekanina, N. Horan, J. Gildersleeve, C. Thompsom, A. Smith, K. Biswas, W. C. Still, and D. Kahne, Parallel synthesis and screening of a solid phase carbohydrate library, Science. 274:1520 (1996).PubMedCrossRefGoogle Scholar
  13. 8.
    C.C. Lenzof, The use of insoluble polymer supports in general organic synthesis, Acc. Chem. Res.. 11:327 (1978).CrossRefGoogle Scholar
  14. 9.
    For a review of solid-phase synthesis of oligosaccharides up to 1980, see J. M. Frechet, In polymer-supported synthesis of oligosaccharides, Hodge, P., Sherrington, D.C., eds., Wiley: Chichester, 407 (1980) and reference cited there. (a) U. Zehavi, and A. Patchornik, Oligosaccharide synthesis on a light-sensitive solid support. the polymer and synthesis of isomaltose( 6-O-a-D-glucopyranosyl-D-glucose). J. Am. Chem. Soc. 95: 5673 (1973) (b) J. M. Frechet, and C. Schuerch, Solid-phase synthesis of oligosaccharides. Preparation of the solid support. poly[p-(l-propen-3-ol-l-yl) styrene], J. Am. Chem. Soc. 93: 492 (1971).Google Scholar
  15. 10.
    G. H. Veeneman, S. Notermans, R. M. Liskamp, G. A. van der Marel, and J. H. van Boom, Solid-phase synthesis of a natually occuring β-(1→5)-linked D-galactofuranosyl heptamer containing the artificial linkage arm L-homoserine, Tetrahedron Lettt. 28: 6695 (1987)CrossRefGoogle Scholar
  16. 11.
    J. Rademann, and R. R. Schmidt, A new method of the solid-phase synthesis of oligosaccharides, Tetrahedron Lett. 37:3989 (1996).CrossRefGoogle Scholar
  17. 12.
    J. A. Hunt, and W. R. Roush, Solid-phase synthesis of 6-deoxyoligosaccharides, J. Am. Chem. Soc. 118:9998 (1996).CrossRefGoogle Scholar
  18. 13.
    K.C. Nicolaou, N. Winssinger, J. Pastor, and F. DeRoose, A general and highly efficient solid phase synthesis of oligosaccharides: total synthesis of a heptasaccharide phytoalexin elicitor (HPE), J. Am. Chem. Soc. 119:449 (1997).CrossRefGoogle Scholar
  19. 14.(a)
    L. Yan, C.M. Taylor, R. Goodnow, and D. Kahne, Glycosylation on the Merrifield resin using anomeric sulfoxides, J. Am. Chem. Soc. 116:6953 (1994).CrossRefGoogle Scholar
  20. 14.(b)
    S. Nilsson, M. Bengtsson, and T. Norberg, Solid-phase synthesis of a fragment of the capsular polysaccharide of haemophilus influenzae type B using H-phosphonate intermediates, J. Carbohydrate chemistry 11:265 (1992).CrossRefGoogle Scholar
  21. 15.
    M. Schuster, P. Wang, J.C. Paulson, and C.H. Wong, Solid-phase chemical-enzymatic synthesis of glycopeptides and oligosaccharide, J. Am. Chem. Soc. 116:1135 (1994).CrossRefGoogle Scholar
  22. 16.
    Y. Ito, O. Kanie, and T. Ogawa, Orthogonal glycosylation strategy for rapid assembly of oligosaccharides on a polymer support, Angew. Chem. Int. Ed. Engl. 35:2510 (1996).CrossRefGoogle Scholar
  23. 17.(a)
    J. Y. Roberge, X. Beebe, and S.J. Danishefsky, A strategy for a convergent synthesis of N-linked glycopeptides on a solid support, Science 269:202 (1995).PubMedCrossRefGoogle Scholar
  24. 17.(b)
    S.J. Danishefky, K.F. McClure, J.T. Randolph, and R.B. Ruggeri, A strategy for the solidphase synthesis of oligosaccharides, Science 260:1307 (1993).CrossRefGoogle Scholar
  25. 17.(c)
    J.T. Randolph, K.F. McClure, and S.J. Danishefky, Major simplifications in oligosaccharide syntheses arising from a solid-phase based method: an application to the synthesis of the Lewis b antigen, J. Am. Chem. Soc. 117:5712 (1995).CrossRefGoogle Scholar
  26. 18.
    U.J. Nilsson, and O. Hindsgaul, Combinatorial michael additions and reductive aminations towards carbohydrate libraries designed to inhibit galactose-binding protein. XVIII International Carbohydrate Symposium. Milano, Italy, Abstract P 212 (1996).Google Scholar
  27. 19.(a)
    H.P. Wessel, C.M. Mitchell, CM. Lobato, and G. Schmid, Saccharide-peptide hybrids as novel oligosaccharide mimetics. Angew. Chem. Int. Ed. Engl. 34:2712 (1995).CrossRefGoogle Scholar
  28. 19.(b)
    E.G. von Roedern, and A. Kessler, A sugar amino acid as a novel peptidomimetic, Angew. Chem. Int. Ed. Engl.. 33:687 (1994).CrossRefGoogle Scholar
  29. 19.(c)
    J.P. McDevitt, and P.T. Lansbury, Glycosamino acid: new building blocks for combinatorial synthesis, J. Am. Chem. Soc. 118:3818 (1996).CrossRefGoogle Scholar
  30. 20.
    M.H.D. Postema, Recent development in the synthesis of C-glycosides, Tetrahedron 48:8545 (1992).CrossRefGoogle Scholar
  31. 21.
    I. Ugi, From isocyanides via four-component condensations to antibiotic synthesis, Angew. Chem. Int. Ed. Engl. 21:810 (1982).CrossRefGoogle Scholar
  32. 22.
    D.P. Sutherlin, T.M. Stark, R. Hughes, and R.W. Armstrong, Generation of C-glycoside peptide ligands for cell surface carbohydrate receptors using a four-component condensation on solid support, J. Org. Chem. 61:8350 (1996).PubMedCrossRefGoogle Scholar
  33. 23.
    W.K. Park, M. Auer, H. Jaksche, and C.H. Wong, Rapid combinatorial synthesis of aminoglycoside antibiotic mimetics: use of a polyethylene glycol-linked amine and a neamine-derived aldehyde in multiple component condensation as a strategy for the discovery of new inhibitors of the HIV RNA rev responsive element, J. Am. Chem. Soc. 118:10150 (1996).CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media New York 1998

Authors and Affiliations

  • Zhi-Guang Wang
    • 1
  • Ole Hindsgaul
    • 1
  1. 1.Department of ChemistryUniversity of AlbertaEdmontonCanada

Personalised recommendations