Skip to main content
Log in

A multi-component reaction (MCR) approach to the synthesis of highly diverse polymers with polypeptide-like features

  • Published:
Molecular Diversity Aims and scope Submit manuscript

Abstract

A new strategy for the combinatorial synthesis of new materials has been developed through the consecutive application of an Ugi 4CC reaction and a ring-opening metathesis polymerization (ROMP) reaction. Norbornenyl aldehydes and carboxylic acids could be used in the Ugi MCR to give highly diverse monomers that were converted to the corresponding polymers by exposure to the second-generation Grubbs' catalyst. These polymers have structural features reminiscent of polypeptides and the process could be extended to the preparation of chiral materials.

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

Access this article

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

Instant access to the full article PDF.

Similar content being viewed by others

References

  1. For examples see: (a) Rishton, G. M., Retz, D. M, Tempest, P. M., Novotny, J., Kahn, J., Treanor, J. S., Lile, J. D. and Citron, M., Fenchylamine sulfonamide inhibitors of ?-amyloi peptide production by the ?-secretase proteolytic pathway: Potential small-molecule therapeutic agents for the treatment of alz heimer's disease, J. Med. Chem., 43 (2000) 2297-2299.

    Google Scholar 

  2. Karan, C. and Miller, B. L. Dynamic diversity in drug discovery: Putting small-molecule evolution to work, Drug Design Trends, 5 (2000) 67-75.

    CAS  Google Scholar 

  3. Frutos, O. and Curran, D., Solution phase synthesis of libraries of polycyclic natural product analogues by cascade radical annulation: synthesis of a 64-member library of mappicine analogues and a 48-member library of mappicine ketone analogues, J. Comb. Chem., 2 (2000) 639-649.

    Article  Google Scholar 

  4. 2. For examples see: (a)_ Uozumi, Y., Mizutani, K. and Nagai, S., A parallel preparation of a bicyclic N-chiral amine library and its use for chiral catalyst screening, Tetrahedron Letter, 42 (2001) 407-410.

    Article  CAS  Google Scholar 

  5. Miller, S. J. and Copeland, G. T. A chemosensor-based approach to catalyst discovery in solution and on solid support, J. Am. Chem. Soc., 121 (1999) 4306-4307.

    Article  Google Scholar 

  6. For an example see: Gilbertson, S. R., Chen, G., Kao, J., Beatty, A. and Campana, C. F., Structure of phosphorouscontaining peptide ligands. X-ray and NMR structural study of free ligand and Rhodium complex, J. Org. Chem., 62 (1997) 5557-5566.

    Article  CAS  Google Scholar 

  7. Xiang, X-D. and Schultz, P. G., Combinatorial approaches to materials science. Current Opinion in Solid State & Materials Science, 3 (1998) 153-158.

    Article  Google Scholar 

  8. Basso, A., Banfi, L., Riva, R., Piaggio, P. and Guanti, G., Solid-phase synthesis of modified oligopeptides via Passerini multicomponent reaction, Tetrahedron Letters, 44 (2003) 2367-2370.

    Article  CAS  Google Scholar 

  9. de Nooy, A. E. J., Masci, G. and Crescenzi, V., Versatile synthesis of polysaccharide hydrogels using the Passerini and Ugi multicomponent condensations, Macromolecules, 32 (1999) 1318-1320.

    Article  CAS  Google Scholar 

  10. Presented in part at The Second International Conference on Multicomponent Reactions, Combinatorial and Related Chemistry, Genoa, Italy, April 14-16, 2003.

  11. Heck, S. and Ugi, I., The multicomponent reactions in the combinatorial synthesis of natural and preparative chemistry, Combinatorial Chemistry & High Throughput Screening, 4 (2001) 1-34.

    Google Scholar 

  12. Ugi, I., Domling, A. and Horl, W., Multicomponent reactions in organic chemistry, Endeavour, 3 (1994) 115.

    Google Scholar 

  13. Trost, B. M. and Hachiya, I., Assymetric molybdenumcatalyzed alkylations, J. Am. Chem. Soc., 120 (1998) 1104-1105.

    Article  CAS  Google Scholar 

  14. Murara, H., Sanda, F. and Endo, T. Highly radicalpolymerizable methacrylamide having dipeptide structure, Macromolecules, 29, (1996) 5535-5538.

    Article  Google Scholar 

  15. Langer, R. Biomaterials in Drug Delivery and Tissue Engineering: One Laboratory's Experience, Acc. Chem. Res., 33 (2000) 94-109.

    Article  CAS  Google Scholar 

  16. For reviews on catalytic olefin metathesis, see: (a) Grubbs, R. H., Miller, S. J., Fu, G. C. Acc. Chem. Res., 28, (1995) 446-452.

    Google Scholar 

  17. Schmalz, H,-G., Angew. Chem., Int. Ed., 34, (1995) 1833-1836.

    Article  CAS  Google Scholar 

  18. Schuster, M. and Blechert, S., Angew. Chem., Int. Ed., 36, (1997) 2036-2056.

    Article  Google Scholar 

  19. Wright, D. L., Curr. Org. Chem., 3, (1999) 211-240.

    CAS  Google Scholar 

  20. Liaw, D.-J, Tsai, J,-S and Wu, P,-L., polynorbornene with cross-linkable side chains via ring-opening metathesis polymerization, Macromolecules, 33 (2000) 6925-6929.

    Article  CAS  Google Scholar 

  21. Nomura, K. and Schrock, R. R., Preparation of 'Sugar-Coated' homopolymers and multiblock ROMP copolymers, Macromolecules, 29 (1996) 540-545.

    Article  CAS  Google Scholar 

  22. Maynard, H. D., Okada, S. and Grubbs, R. H., Synthesis of Norbornenyl polymers with bioactive Oligopeptides by ring-opnening metathesis polymerization, Macromolecules, 33 (2000) 6239-6248.

    Article  CAS  Google Scholar 

  23. Roberts, K. S. and Sampson, N. S., Increased Polymer Length of Oligopeptide-Substituted Polynorbornenes with LiCl, J. Org. Chem., 68 (2003), 2020-2023.

    Article  CAS  Google Scholar 

  24. I. Ugi, U. Fetzer, U. Eholzer, H. and Knupfer, K., Neuere Methoden der präparativen organischen Chemie IV. Isonitril-Synthesen, Angew. Chem., 77 (1965) 492-504; Angew. Chem. Int. Ed. Engl., 4 (1965) 452-464.

  25. Trnka, T. M. and Grubbs, R. H., The development of L2X2 R = CHR olefin metathesis catalysts: An organometallic success story, Acc. Chem. Res., 34 (2000) 18-29.

    Article  Google Scholar 

  26. Bielawski, C. W. and Grubbs, R. H., Highly efficient ring-opening metathesis polymerization (ROMP) using new Ruthenium catalysts containing N-heterocyclic carbene ligands, Angew. Chem. Int., Ed., 39 (2000) 2903-2906.

    Article  CAS  Google Scholar 

  27. Corey, E. J., Shibata, T. and Lee, T. W., Asymmetric Diels-Alder reactions catalyzed by a triflic acid activated chiral oxazaborolidine, J. Am. Chem. Soc., 124 (2002) 3808-3809.

    Article  CAS  Google Scholar 

  28. Sheldrick, G. M. (1998). SHELXTL5. Bruker-AXS, Madison, Wisconsin, USA.

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Robotham, C.V., Baker, C., Cuevas, B. et al. A multi-component reaction (MCR) approach to the synthesis of highly diverse polymers with polypeptide-like features. Mol Divers 6, 237–244 (2003). https://doi.org/10.1023/B:MODI.0000006777.63423.40

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1023/B:MODI.0000006777.63423.40

Navigation