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Combinatorial synthesis of small-molecule libraries using 3-amino-5-hydroxybenzoic acid

Summary

A non-peptide library of 2001 compounds has been prepared utilizing solid-phase techniques. The split/combine method was demonstrated to work well to form mixtures of compounds based on 3-amino-5-hydroxybenzoic acid as a core structure. The benzoic acid of the core structure served as the attachment point for the resin and the amino and hydroxy positions were variably substituted.

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References

  1. 1 a.

    For peptides see: 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 and references cited therein.

  2. 1 b.

    For oligosaccharides and glycopeptides see: Polt, R., Szabó, L., Treiberg, J., Li, Y. and Hruby, V.J.,General methods for α- or β-O-Ser/Thr glycosides and glycopeptides. Solid-phase synthesis of O-glycosyl cyclic enkephalin analogues, J. Am. Chem. Soc., 114 (1992) 10249–10258.

  3. 1 c.

    Verduyn, R., Van der Klein, P.A.M., Douwes, M., Van der Marel, G.A. and Van Boom, J.H.,Polymer-supported solution synthesis of a heptaglucoside having phytoalexin elicitor activity, Recl. Trav. Chim. Pays-Bas, 112 (1993) 464–466.

  4. 1 d.

    Yan, L., Taylor, C.M., Goodnow Jr., R. and Kahne, D.,Glycosylation on the Merrifield resin using anomeric sulfoxides, J. Am. Chem. Soc., 116 (1994) 6953–6954 and references cited therein.

  5. 1 e.

    For oligonucleotides see: Letsinger, R.L. and Mahadevan, V.,Stepwise synthesis of oligodeoxyribonucleotides on an insoluble polymer support, J. Am. Chem. Soc., 88 (1966) 5319–5324.

  6. 1 f.

    Beaucage, S.L. and Iyer, R.P.,Advances in the synthesis of oligonucleotides by the phosphoramidate approach, Tetrahedron, 48 (1992) 2223–2311.

  7. 1 g.

    Reddy, M.P., Michael, M.A., Faroqui, F. and Giorgis, N.S.,New and efficient solid support for the synthesis of nucleic acids, Tetrahedron Lett., 35 (1994) 5771–5774.

  8. 1 h.

    For unnatural biopolymers see: Zuckermann, R.N., Kerr, J.M., Kent, S.B.H. and Moos, W.H.,Efficient method for the preparation of peptiods [oligo(N-substituted glycines) ] by submonomer solid-phase synthesis, J. Am. Chem. Soc., 114 (1992) 10646–10647.

  9. 1 i.

    Cho, C.Y., Moran, E.J., Cherry, S.R., Stephans, J.C., Fodor, S.P.A., Adams, C.L., Sundaram, A., Jacobs, J.W. and Schultz, P.G.,An unnatural biopolymer, Science, 261 (1993) 1303–1305.

  10. 2 a.

    Leznoff, C.C.,The use of insoluble polymer supports in organic chemical synthesis, Chem. Soc. Rev., (1974) 65–85.

  11. 2 b.

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

  12. 2 c.

    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 and references cited therein.

  13. 2 d.

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

  14. 2 e.

    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 and references cited therein.

  15. 3

    Furka, A., Sebestyén, F., Asgedom, M. and Dibó, G.,General method for rapid synthesis of multicomponenl peptide mixtures, Int. J. Pept. Protein Res., 37 (1991) 487–493.

  16. 4

    Becker, A.M., Rickards, R.W. and Brown, R.F.C.,An expedient synthesis of 3-amino-5-hydroxybenzoic acid and its N-alkyl analogues, Tetrahedron, 39 (1983) 4189–4192.

  17. 5

    Abraham, D.J., Gazze, D.M., Kennedy, P.E. and Makotoff, M.,Design, synthesis, and testing of potential antisickling agents. 5. Disubstituted benzoic acids designed for the donor site and proline salicylates designed for the acceptor site, J. Med. Chem., 27 (1984) 1549–1559.

  18. 6 a.

    Daines, R.A. and Kingsbury, W.D.,Benzoic acid derivatives, International Patent WO 91/18601, 1991.

  19. 6 b.

    Chambers, P.A., Daines, R.A., Jakas, D.R., Kingsbury, W.D. and Pendrak, I.,Pyridine compounds for treating leukotrienerelated diseases, International Patent WO 93/06085, 1993.

  20. 7

    Betts, M.J., Davies, G.M. and Swain, M.L.,Carbapenems containing a carboxy substituted phenyl group, processes for their preparation, intermediates and use as antibiotics, International Patent WO 93/15078, 1993.

  21. 8

    Howe, R. and Smith, L.H.,Alkanolamine derivatives — beta-adrenergic blocking agents, U.S. Patent 3,712,927, 1973.

  22. 9

    Rink, H.,Solid-phase synthesis of protected peptide fragments using a trialkoxy-diphenyl-methylester resin, Tetrahedron Lett., 28 (1987) 3787–3790.

  23. 10

    Simon, R.J., Kania, R.S., Zuckermann, R.N., Huebner, V.D., Jewell, D.A., Banville, S., Ng, S., Wang, L., Rosenberg, S., Marlowe, C.K., Spellmeyer, D.C., Tan, R., Frankel, A.D., Santi, D.V., Cohen, F.E. and Bartlett, P.A.,Peptoids: A modular approach to drug discovery, Proc. Natl. Acad. Sci. USA, 89 (1992) 9367–9371.

  24. 11

    Carpino, L.A., El-Faham, A., Minro, C.A. and Albericio, F.,Advantageous applications of azobenzotriazole (triazolopyridine)-based coupling reagents to solid-phase peptide synthesis, J. Chem. Soc., Chem. Commun., (1994) 201–203.

  25. 12

    Zaugg, H.E.,Selective cleavage of aryl esters by anhydrous alkali carbonates, J. Org. Chem., 41 (1976) 3419–3421.

  26. 13

    Mergler, M., Tanner, R., Gosteli, J. and Grogg, P.,Peptide synthesis by a combination of solid-phase and solution methods I: A new very acid-labile anchor group for the solid phase synthesis of fully protected fragments, Tetrahedron Lett., 29 (1988) 4005–4008.

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Correspondence to Sharon M. Dankwardt.

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Dankwardt, S.M., Phan, T.M. & Krstenansky, J.L. Combinatorial synthesis of small-molecule libraries using 3-amino-5-hydroxybenzoic acid. Mol Divers 1, 113–120 (1996). https://doi.org/10.1007/BF01721326

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Keywords

  • Solid-phase synthesis
  • Combinatorial approach
  • Non-peptide library
  • 3-Amino-5-hydroxybenzoic acid