Synthesis of biosynthetic precursors of chromophores of red fluorescent proteins

  • P. E. Ivashkin
  • K. A. Lukyanov
  • I. V. Yampolsky


A method for the synthesis of 5-arylidene-3,5-dihydro-4H-imidazol-4-ones corresponding to the chromophore of the green fluorescent protein (GFP) with acylaminoalkyl substituents at position 2 of the imidazolone core has been developed. These biomimetic model compounds are the precursors of the chromophores of red fluorescent proteins. The method is based on the masking of the dehydrotyrosine fragment of target compounds by the β-hydroxytyrosine moiety. The key stages of the synthesis include the condensa-tion of β-hydroxytyrosine with the appropriate N-acetylamino acid, the unmasking of dehydrotyrosine by O-acylation with subsequent elimination, and the cyclization of the resulting 3-acylaminocinnamic acid derivatives in basic medium.


chromophore imidazolone green fluorescent protein GFP DsRed 







the red fluorescent protein of the coral polyp Discosoma


electrospray ionization


green fluorescent protein




matrix-assisted laser desorption ionization








  1. 1.
    Ivashkin, P.E., Yampol’skii, I.V., and Luk’yanov, K.A., Bioorg. Khim., 2009, vol. 35, pp. 726–743 [Russ. J. Bioorg. Chem. (Engl. Transl.), 2009, vol. 35, pp. 652–669].PubMedGoogle Scholar
  2. 2.
    Niwa, H., Inouye, S., Hirano, T., Matsuno, T., Kojima, S., Kubota, M., Ohashi, M., and Tsuji, F., Proc. Natl. Acad. Sci. USA, 1996, vol. 93, pp. 13617–13622.PubMedCrossRefGoogle Scholar
  3. 3.
    Yampolsky, I.V., Remington, S.J., Martynov, V.I., Potapov, V.K., Lukyanov, S., and Lukyanov, K.A., Biochemistry, 2005, vol. 44, pp. 5788–5793.PubMedCrossRefGoogle Scholar
  4. 4.
    Yampolsky, I.V., Kislukhin, A.A., Amatov, T.T., Shcherbo, D., Potapov, V.K., Lukyanov, S., and Lukyanov, K.A., Bioorg. Chem., 2008, vol. 36, pp. 96–104.PubMedGoogle Scholar
  5. 5.
    Yampolsky, I.V., Balashova, T.A., and Lukyanov, K.A., Biochemistry, 2009, vol. 48, pp. 8077–8082.PubMedCrossRefGoogle Scholar
  6. 6.
    Kojima, S., Ohkawa, H., Hirano, T., Maki, S., Niwa, H., Ohashi, M., Inouye, S., and Tsuji, F.I., Tetrahedron Lett., 1998, vol. 39, pp. 5239–5242.CrossRefGoogle Scholar
  7. 7.
    Devasia, G.M., Tetrahedron Lett., 1976, vol. 17, pp. 571–572.CrossRefGoogle Scholar
  8. 8.
    Ekeley, J.B. and Ronzio, A.R., J. Am. Chem. Soc., 1935, vol. 57, pp. 1353–1356.CrossRefGoogle Scholar
  9. 9.
    Kidwai, A.R. and Devasia, G.M., J. Org. Chem., 1962, vol. 27, pp. 4527–4531.CrossRefGoogle Scholar
  10. 10.
    Wu, L. and Burgess, K., J. Am. Chem. Soc., 2008, vol. 130, pp. 4089–4096.PubMedCrossRefGoogle Scholar
  11. 11.
    Oumouch, S., Bourotte, M., Schmitt, M., and Bourguignon, J.-J., Synthesis, 2005, pp. 25–27.Google Scholar
  12. 12.
    Rao, Y.S. and Filler, R., Synthesis, 1975, pp. 749–764.Google Scholar
  13. 13.
    Tripathy, K.P. and Mukerjee, A.K., Synthesis, 1985, pp. 285–288.Google Scholar
  14. 14.
    Boyd, V.L., Bozzini, M., Guga, P.J., DeFranco, R.J., Yuan, P.-M., Loudon, G.M., and Nguyen, D., J. Org. Chem., 1995, vol. 60, pp. 2581–2587.CrossRefGoogle Scholar
  15. 15.
    Kojima, S., Hirano, T., Niwa, H., Ohashi, M., Inouye, S., and Tsuji, F.I., Tetrahedron Lett., 1997, vol. 38, pp. 2875–2878.CrossRefGoogle Scholar
  16. 16.
    Boger, D.L., Cerbone, L.R., and Yohannes, D., J. Org. Chem., 1988, vol. 53, pp. 5163–5166.CrossRefGoogle Scholar
  17. 17.
    Martin, T. and Moody, C.J., J. Chem. Soc., Perkin Trans., 1988, pp. 235–242.Google Scholar
  18. 18.
    Bolhofer, W.A., J. Am. Chem. Soc., 1954, vol. 76, pp. 1322–1326.CrossRefGoogle Scholar
  19. 19.
    Shigematsu, N., Kayakiri, N., Okada, S., and Tanaka, H., Chem. Pharm. Bull., 1997, vol. 45, pp. 236–242.PubMedGoogle Scholar
  20. 20.
    Tanabe, T., Yajima, S., and Imaida, M., Bull. Chem. Soc. Jpn., 1968, vol. 41, pp. 2178–2179.CrossRefGoogle Scholar
  21. 21.
    Williams, M.E., Masui, H., Long, J.W., Malik, J., and Murray, R.W., J. Am. Chem. Soc., 1997, vol. 119, pp. 1997–2005.CrossRefGoogle Scholar
  22. 22.
    Dong, X., Zhang, Z., Wen, R., Shen, J., Shen, X., and Jiang, H., Bioorg. Med. Chem. Lett., 2006, vol. 16, pp. 5913–5916.PubMedCrossRefGoogle Scholar

Copyright information

© Pleiades Publishing, Ltd. 2011

Authors and Affiliations

  • P. E. Ivashkin
    • 1
  • K. A. Lukyanov
    • 1
  • I. V. Yampolsky
    • 1
  1. 1.Shemyakin-Ovchinnikov Institute of Bioorganic ChemistryRussian Academy of SciencesMoscowRussia

Personalised recommendations