Skip to main content
Log in

Multiple simultaneous synthesis of phenolic libraries

  • Research Papers
  • Published:
Molecular Diversity Aims and scope Submit manuscript

Summary

A series of analogous arrays of small, non-peptidyl, non-oligomeric compounds were synthesized on polystyrene resin. With the aid of a functionally differentiated phenolic scaffold, the batch preparation of unique benzamide and urea resins was accomplished, which were further derivatized in modified 96-well plates. An efficient cleavage reaction of the phenyl benzoate link enabled the isolation of more than 600 phenolic compounds in milligram quantities that were suitable for direct biological screening. The technology described herein represents a facile, economical approach to non-peptidyl chemical diversity.

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. Moos, W.H., Green, G.D. and Pavia, M.R.,Recent advances in the generation of molecular diversity, Annu. Rep. Med. Chem., 28 (1993) 315–324.

    Google Scholar 

  2. Gracheck, S.J., Miller, P.F. and Marks, J.S.,Recent developments in cell based mechanism screening, Annu. Rep. Med. Chem., 28 (1993) 161–167.

    Google Scholar 

  3. Pavia, M.R., Sawyer, T.K. and Moos, W.H.,The generation of molecular diversity, Bioorg. Med. Chem. Lett., 3 (1993) 387–396.

    Google Scholar 

  4. Gallop, M.A., Barrett, R.W., Dower, W.J., Fodor, S.P.A. and Gordon, E.M.,Applications of combinatorial technologies to drug discovery. 1. Background and peptide combinatorial libraries, J. Med. Chem., 37 (1994) 1233–1251.

    Google Scholar 

  5. Gordon, E.M., Barrett, R.W., Dower, W.J., Fodor, S.P.A. and Gallop, M.A.,Applications of combinatorial technologies to drug discovery. 2. Combinatorial organic synthesis, library screening strategies, and future directions, J. Med. Chem., 37 (1994) 1385–1401.

    Google Scholar 

  6. Zuckermann, R.N.,The chemical synthesis of peptidomimetic libraries, Curr. Opin. Struct. Biol., 3 (1993) 580–584.

    Google Scholar 

  7. Liskamp, R.M.J.,Opportunities for new chemical libraries: Unnatural biopolymers and diversomers, Angew. Chem., Int. Ed. Engl., 33 (1994) 633–636.

    Google Scholar 

  8. Bunin, B.A. and Ellman, J.A.,General and expedient method for the solid-phase synthesis of 1,4-benzodiazepine derivatives, J. Am. Chem. Soc., 114 (1992) 10997–10998.

    Google Scholar 

  9. DeWitt, S.H., Kiely, J.S., Stankovic, C.J., Schroeder, M.C., Reynolds Cody, D.M. and Pavia, M.R., ‘Diversomers’:An approach to nonpeptide, nonoligomeric chemical diversity, Proc. Natl. Acad. Sci. USA, 90 (1993) 6909–6913.

    Google Scholar 

  10. Chen, C., Ahlberg Randall, L.A., Miller, R.B., Jones, A.D. and Kurth, M.J., ‘Analogous’organic synthesis of small-compound libraries: Validation of combinatorial chemistry in small-molecule synthesis, J. Am. Chem. Soc., 116 (1994) 2661–2662.

    Google Scholar 

  11. Hutchins, S.M. and Chapman, K.T.,A general method for the solid phase synthesis of ureas, Tetrahedron Lett., 35 (1994) 4055–4058.

    Google Scholar 

  12. Bunin, B.A., Plunkett, M.J. and Ellman, J.A.,The combinatorial synthesis and chemical and biological evaluation of a 1,4-benzodiazepine library, Proc. Natl. Acad. Sci. USA, 91 (1994) 4708–4712.

    Google Scholar 

  13. Kurth, M.J., Ahlberg Randall, L.A., Chen, C., Melander, C., Miller, R.B., McAlister, K., Reitz, G., Kang, R., Nakatsu, T. and Green, C.,Library-based lead compound discovery: Antioxidants by an analogous synthesisldeconvolutive assay strategy, J. Org. Chem., 59 (1994) 5862–5864.

    Google Scholar 

  14. Backes, B.J. and Ellman, J.A.,Carbon-carbon bond forming methods on solid support. Utilization of Kenner's ‘safety-catch’ linker, J. Am. Chem. Soc., 116 (1994) 11171–11172.

    Google Scholar 

  15. Brenner, S. and Lerner, R.A.,Encoded combinatorial chemistry, Proc. Natl. Acad. Sci. USA, 89 (1992) 5381–5383.

    Google Scholar 

  16. Kerr, J.M., Banville, S.C. and Zuckermann, R.N.,Encoded combinatorial peptide libraries containing non-natural amino acids, J. Am. Chem. Soc., 115 (1992) 2529–2531.

    Google Scholar 

  17. Nielsen, J., Brenner, S. and Janda, K.D.,Synthetic methods for the implementation of encoded combinatorial chemistry, J. Am. Chem. Soc., 115 (1993) 9812–9813.

    Google Scholar 

  18. Needels, M.C., Jones, D.G., Tate, E.H., Heinkel, G.L., Kochersperger, L.M., Dower, W.J., Barrett, R.W. and Gallop, M.A.,Generation and screening of an oligonucleotide-encoded synthetic peptide library, Proc. Natl. Acad. Sci. USA, 90 (1993) 10700–10704.

    Google Scholar 

  19. Ohlmeyer, M.H., Swanson, R.N., Dillard, L.W., Reader, J.C., Asouline, G., Kobayashi, R., Wigler, M. and Still, W.C.,Complex synthetic chemical libraries indexed with molecular tags, Proc. Natl. Acad. Sci. USA, 90 (1993) 10922–10926.

    Google Scholar 

  20. Nestler, H.P., Bartlett, P.A. and Still, W.C.,A general method for molecular tagging of encoded combinatorial chemistry libraries, J. Org. Chem., 59 (1994) 4723–4724.

    Google Scholar 

  21. Janda, K.D.,Tagged versus untagged libraries: methods for the generation and screening of combinatorial chemical libraries, Proc. Natl. Acad. Sci. USA, 91 (1994) 10779–10785.

    Google Scholar 

  22. Farall, M.J. and Frechet, J.M.J.,Bromination and lithiation: Two important steps in the functionalization of polystyrene resins, J. Org. Chem., 41 (1976) 3877–3882.

    Google Scholar 

  23. Pinori, M., Di Gregorio, G. and Mascagni, P.,A new anchor group for the solid-phase synthesis of C-terminal peptide amides in neutral conditions, In Epton, R. (Ed.) Innovation and Perspectives in Solid Phase Synthesis, Mayflower Worldwide, Kingswinford, 1994, p. 635.

    Google Scholar 

  24. CAmps, F., Cartells, J. and Pi, J.,Organic synthesis with functionalized polymers IV, Anales Quim., 70 (1974) 848–849.

    Google Scholar 

  25. Rapoport, H. and Crowley, J.I.,Solid phase organic synthesis: Novelty or fundamental concept?, Acc. Chem. Res., 9 (1976) 135–144.

    Google Scholar 

  26. Leznoff, C.C.,The use of insoluble polymer supports in general organic synthesis, Acc. Chem. Res., 11 (1978) 327–333.

    Google Scholar 

  27. Kulanthaivel, P., Hallock, Y.F., Boros, C., Hamilton, S.M., Janzen, W.P., Ballas, L.M., Loomis, C.R. and Jiang, J.B.,Balanol: A novel and potent inhibitor of protein kinase C from the fungus Verticillium bananoides, J. Am. Chem. Soc., 115 (1993) 6452–6453.

    Google Scholar 

  28. Onoda, T., Iinuma, H., Sasaki, Y., Hamada, M., Isshiki, K., Naganawa, H., Takeuchi, T., Tatsuta, K. and Umezawa, K.,Isolation of a novel tyrosine kinase inhibitor, lavendustin A, from Streptomyces griseolavendus, J. Nat. Prod., 52 (1989) 1252–1257.

    Google Scholar 

  29. Giralt, E., Rizo, J. and Pedroso, E.,Application of gel-phase 13 C-NMR to monitor solid phase peptide synthesis, Tetrahedron, 40 (1984) 4141–4152

    Google Scholar 

  30. Look, G.C., Holmes, C.P., Chinn, J.P. and Gallop, M.A.,Methods for combinatorial organic synthesis: The use of fast 13 C NMR analysis for gel phase reaction monitoring, J. Org. Chem., 59 (1994) 7588–7590.

    Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Meyers, H.V., Dilley, G.J., Durgin, T.L. et al. Multiple simultaneous synthesis of phenolic libraries. Mol Divers 1, 13–20 (1995). https://doi.org/10.1007/BF01715805

Download citation

  • Received:

  • Accepted:

  • Issue Date:

  • DOI: https://doi.org/10.1007/BF01715805

Keywords

Navigation