Skip to main content
SpringerLink
Log in

Solid-supported reagents and catalysts for the preparation of large ring compounds

  • Review
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

Parallel combinatorial synthesis in solution using immobilized reagents, catalysts, and scavengers has emerged as a powerful technique for the preparation of diverse libraries of compounds. This technique has only recently been applied to the synthesis of large-ring compounds. In this comprehensive review several strategies are presented and discussed, including Pd-catalyzed allylic alkylation, Stille-coupling, macrolactonization and macrolactamization using solid supported reagents and catalysts. In several cases site isolation has allowed operation of these macrocyclization reactions in concentrated solution (pseudo-dilution effect).

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

Abbreviations

DBU:

1,8-diazabicyclo[5.4.0]undec-7ene

DEAD:

Di(ethyl)azodicarboxylate

DIAD:

Di(isopropyl)azodicarb oxylate

DMAP:

N,N-Dimethyl-4-aminopyridine

dppe:

Bis(diphenylphosphino)ethane

dppf:

1,1′-Bis(diphenylphosphino) ferrocene

Eq.:

Equivalent

HOBT:

1-Hydroxybenzotriazole

PDBU:

polystyrene-supported 1, 8-diazabicyclo[5.4.0]undec-7ene

PEG:

Polyethylenglykol

PS:

Polystyrene

References

  1. Roxburgh, C.J., The syntheses of large-ring compounds, Tetrahedron, 51 (1995) 9767–9822.

    Google Scholar 

  2. Lambert, J.N., Mitchell, J.P. and Roberts, K.D., The synthesis of cyclic peptides, J. Chem. Soc., Perkin Trans., 1 (2001) 471–484.

    Google Scholar 

  3. Li, P. and Roller, P.P, Cyclization strategies in peptide derived drug design, Curr. Top. Med. Chem., 2 (2002) 325–341.

    Google Scholar 

  4. Masamune, S., Bates, G.S. and Corcoran, J.W., Makrolide. neuere fortschritte ihrer chemie und biochemie, Angew. Chem., 89 (1977) 602–624.

    Google Scholar 

  5. Rousseau, G., Medium ring lactones, Tetrahedron, 51 (1995) 2777–2849.

    Google Scholar 

  6. Nicolaou, K.C., Synthesis of macrolides, Tetrahedron, 33 (1977) 683–710.

    Google Scholar 

  7. Golebiowski, A., Klopfenstein, S.R. and Portlock, D.E., Lead compounds discovered from libraries, Curr. Opin. Chem. Biol., 5 (2001) 273–284.

    Google Scholar 

  8. Golebiowski, A., Klopfenstein, S.R. and Portlock, D.E., Lead compounds discovered from libraries: Part 2, Curr. Opin. Chem. Biol., 7 (2003) 308–325.

    Google Scholar 

  9. Dolle, R.E., Comprehensive survey of combinatorial library synthesis: 2002, J. Comb. Chem., 5 (2003) 693–753.

    Google Scholar 

  10. Dolle, R.E., Comprehensive survey of combinatorial library synthesis: 2001, J. Comb. Chem., 4 (2002) 369–418.

    Google Scholar 

  11. Dolle, R.E., Comprehensive survey of combinatorial library synthesis: 2000, J. Comb. Chem., 3 (2001) 477–517.

    Google Scholar 

  12. Dolle, R.E., Comprehensive survey of combinatorial library synthesis: 1999, J. Comb. Chem., 2 (2000) 383–433.

    Google Scholar 

  13. Dolle, R.E., Comprehensive survey of combinatorial library synthesis: 1998, J. Comb. Chem., 1 (1999) 235–282.

    Google Scholar 

  14. Dolle, R.E., Comprehensive survey of chemical libraries yielding enzyme inhibitors, receptor agonists and antagonists, and other biologically active agents: 1992 through 1997, Mol. Div., 3 (1998) 199–233.

    Google Scholar 

  15. Dolle, R.E., Comprehensive survey of combinatorial libraries with undisclosed biological activity: 1992 through 1997, Mol. Div., 3 (1998) 233–256.

    Google Scholar 

  16. Nicolaou, K.C., Winssinger, N., Pastor, J., Ninkovic, S., Sarabia, F., He, Y., Vourloumis, D., Yang, Z., Li, T., Giannakakou, P. and Hamel, E., Synthesis of epothilones A and B in solid and solution phase, Nature, 387 (1997) 268–272.

    Google Scholar 

  17. Nicoloau, K.C., Winssinger, N., Pastor, J. and Murphy, F., Solid Phase Synthesis of Macrocyclic Systems by a Cyclorelease Strategy. Application of the Stille Coupling to a Synthesis of (S)-Zearalenone, Angew. Chem. Int. Ed., 37 (1998) 2534–2537.

    Google Scholar 

  18. Kiselyov, A.S., Eisenberg, S. and Luo, Y., Solid support synthesis of 14-membered macrocycles via SNAr methodology on acrylate resin, Tetrahedron Lett., 40 (1999) 2465–2468.

    Google Scholar 

  19. Bourne, G.T., Golding, S.W., McGeary, R.P., Meeutermans, W.D.F., Jones, A., Marshall, G.R., Alewood, P.F. and Smythe M.L., The development and application of a novel safety-catch linker for BOC-based assembly of libraries of cyclic peptides, J. Org. Chem., 66 (2001) 7706–7713.

    Google Scholar 

  20. Seitz, O., Die cyclisierende ablösung, Nachr. Chem., 49 (2001) 912–916.

    Google Scholar 

  21. Kirschning, A., Monenschein, H. and Wittenberg, R., Functionalized polymers—emerging versatile tools for solution-phase chemistry and automated parallel synthesis, Angew. Chem. Int. Ed., 40 (2001) 650–679.

    Google Scholar 

  22. Ley, S.V., Baxendale, I.R., Bream, R.N., Jackson, P.S., Leach, A.G., Longbottom, D.A., Nesi, M., Scott, J.S., Storer, R.I. and Taylor, S.J., Multi-step organic synthesis using solid-supported reagents and scavengers: A new paradigm in chemical library synthesis, J. Chem. Soc., Perkin Trans. 1 (2000) 3815–4195.

    Google Scholar 

  23. Parlow, J.J., Devraj, R.V. and South, M.S., Solution-phase chemical library synthesis using polymer-assisted purification techniques, Curr. Opin. Chem. Biol., 3 (1999) 320–336.

    Google Scholar 

  24. Kaldor, S.W. and Siegel, M.G., Combinatorial chemistry using polymer-supported reagents, Curr. Opin. Chem. Biol., 1 (1997) 101–106.

    Google Scholar 

  25. McNamara, C.A., Dixon, M.J. and Bradley, M., Recoverable catalysts and reagents using recyclable polystyrene-based supports, Chem. Rev., 102 (2002) 3275–3300.

    Google Scholar 

  26. Clapham, B., Reger, T.S. and Janda, K.D., Polymer-supported catalysis in synthetic organic chemistry, Tetrahedron, 57 (2001) 4637–4662.

    Google Scholar 

  27. Scott, L.T. and Naples, J.O., Macrolide synthesis by the polystyrene-mediated lactonization of ω-hydroxycarboxylic acids, Synthesis, (1976) 738–739.

  28. Regen, S.L. and Kimura, Y., Triphase catalytic cyclization. Efficiacious macrolide synthesis, J. Am. Chem. Soc., 104 (1982) 2064–2065.

    Google Scholar 

  29. Regen, S.L. and Kimura, Y., High dilution via solid–liquid phase transfer catalysis. A practical approach to the synthesis of macrolides, J. Org. Chem., 48 (1983) 1533–1534.

    Google Scholar 

  30. Hodge, P., Ji-Long, J., Owen, G.J. and Houghton, M.P., Reactions of polymer-supported ω-bromoalkylcarboxylates: Formation of lactones versus oligomerization, Polymer, 37 (1996) 505–5067.

    Google Scholar 

  31. Tomoi, M., Watanabe, T., Suzuki, T. and Kakiuchi, H., Macrolide synthesis from ω-bromocarboxylic acids using polymer-supported 1,8-diazabicyclo[5.4.0]undec-7-ene, Macromol. Chem., 186 (1985) 2473–2481.

    Google Scholar 

  32. Amos, R.A., Emblidge, R.W. and Havens, N., Esterification using a polymer-supported phosphine reagent, J. Org. Chem., 48 (1983) 3598–3600.

    Google Scholar 

  33. Herb, C. and Maier, M.E., A Formal Total Synthesis of the Salicylhalamides, J. Org. Chem., 68 (2003) 8129–8135.

    Google Scholar 

  34. Boden, E.P. and Keck, G.E., Proton-transfer steps in Steglich esterification: A very practical new method for macrolactonization, J. Org. Chem., 50 (1985) 2394–2395.

    Google Scholar 

  35. Keck, G.E., Sanchez, C. and Wager, C.A., Macrolactonization of hydroxyl acids using a polymer bound carbodiimide, Tetrahedron Lett., 41 (2000) 8673–8676.

    Google Scholar 

  36. Storer, R.I., Takemoto, T., Jackson, P.S. and Ley, S.V., A total synthesis of epothilones using solid-supported reagents and scavengers, Angew. Chem. Int. Ed., 42 (2003) 2521–2525.

    Google Scholar 

  37. Inanaga, J., Hirata, K., Saeki, H., Katsuki, H. and Yamaguchi, M., A rapid esterificaion by means of mixed anhydride and its application to large-ring lactonization, Bull. Chem. Soc. Jpn., 52 (1979) 1989–1973.

    Google Scholar 

  38. Huang, W. and Kalivretenos, A.G., Synthesis of medium ring lactams Via cyclization reactions using polymer bound HOBT as catalyst, Tetrahedron Lett., 36 (1996) 9113–9116.

    Google Scholar 

  39. Trost, B.M. and Warner, R.W., Makrocyclization via an isomerization reaction at high concentrations promoted by palladium templates, J. Am. Chem. Soc., 104 (1982) 6112–6114.

    Google Scholar 

  40. Trost, B.M. and Warner, R.W., Macrolide formation via an isomerization reaction. An unusual dependence on nucleophile, J. Am. Chem. Soc., 105 (1983) 5940–5942.

    Google Scholar 

  41. Trost, B.M., Cyclizations via palladium-catalyzed allylic alkylations, Angew. Chem. Int. Ed. Engl., 28 (1999) 1173–1192.

    Google Scholar 

  42. Fürstner, A. and Weintritt, H., Total synthesis of roseophilin, J. Am. Chem. Soc., 120 (1998) 2817–2825.

    Google Scholar 

  43. Stille, J.K., Su, H., Hill, D.H., Schneider, P., Tanaka, M., Morrison, D.L. and Hegedus, L.S., Synthesis of large-ring keto lactones by the homogeneous and polymer-supported palladium-catalyzed carbonylative coupling of esters having vinyl triflate and vinylstannane termini, Organometallics, 10 (1991) 1993–2000.

    Google Scholar 

  44. Barrett, A.G.M., Hennessy, A.J., Le Vezouet, R., Procopiou, P.A., Seale, P.W., Stefaniak, S., Upton, R.J., White, A.J.P. and Williams, D.J., Synthesis of diverse macrocyclic peptidomimetics utilizing ring-closing metathesis and solid-phase synthesis, J. Org. Chem, 69 (2004) 1028–1037.

    Google Scholar 

  45. Annis, I., Chen, L. and Barany, G., Novel solid-phase reagents for facile formation of intramolecular disulfide bridges in peptides under mild conditions, J. Am. Chem. Soc., 120 (1998) 7226–7238.

    Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Fachbereich Chemie, University Dortmund, Dortmund, Germany

    Elisabeth Gonthier & Rolf Breinbauer

  2. Max-Planck-Institute for Molecular Physiology, Dortmund, Germany

    Rolf Breinbauer

Authors
  1. Elisabeth Gonthier
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rolf Breinbauer
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rolf Breinbauer.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Gonthier, E., Breinbauer, R. Solid-supported reagents and catalysts for the preparation of large ring compounds. Mol Divers 9, 51–62 (2005). https://doi.org/10.1007/s11030-005-1308-8

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11030-005-1308-8

Keywords

Search

Navigation