, Volume 44, Issue 5, pp 447–449 | Cite as

Analysis of structural features responsible for the sweetness of the sesquiterpene, hernandulcin

  • C. M. Compadre
  • R. A. Hussain
  • R. L. de Compadre Lopez
  • J. M. Pezzuto
  • A. D. Kinghorn
Short Communications


The relationship between sweetness and structure was studied for several analogues of the intensely sweet sesquiterpene, hernandulcin. These derivatives were prepared synthetically, and were subjected to spectroscopic and conformational analysis. With the exception of the parent substance, none of the derivatives tested proved to be sweet. Evidence gathered in this study suggests that hernandulcin binds to its putative receptor through a three-point interaction, involving the C-1 carbonyl and C-1′ hydroxyl groups, and the double bond between C-4′ and C-5′. In the course of a preliminary safety assessment, the 3-desmethyl derivative of hernandulcin was found to be mutagenic towardSalmonella typhimurium strain TM677.

Key words

Hernandulcin intense sweetener synthetic analogues taste attributes conformational analysis structure-activity relationships safety assessment 


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 3.
    Kinghorn, A. D. and Compadre, C. M., Pharm. Int.6 (1985) 201.Google Scholar
  2. 4.
    O'Brien Nabors, L., and Gelardi, R. C. (Eds), Alternative Sweeteners. Marcel Dekker, New York and Basel 1986.Google Scholar
  3. 5.
    Birch, G. G., Endeavour, New Series11 (1987) 21.Google Scholar
  4. 6.
    Temussi, P. A., Lelj, F., Tancredi, T., Castiglione-Morelli, M. A., and Pastore, A., Int. J. Quantum Chem.26 (1984) 889.CrossRefGoogle Scholar
  5. 7.
    DuBois, G. E., A. Rep. Med. Chem.17 (1982) 323.Google Scholar
  6. 8.
    Compadre, C. M., Pezzuto, J. M., Kinghorn, A. D., and Kamath, S. K., Science227 (1985) 417.PubMedGoogle Scholar
  7. 9.
    Compadre, C. M., Hussain, R. A., Lopez de Compadre, R. L., Pezzuto, J. M., and Kinghorn, A. D., J. agric. Fd Chem.35 (1987) 273.CrossRefGoogle Scholar
  8. 10.
    Mori, K., and Kato, M., Tetrahedron42 (1986) 5895.CrossRefGoogle Scholar
  9. 11.
    Pezzuto, J. M., Compadre, C. M., Swanson, S. M., Nanayakkara, N. P. D., and Kinghorn, A. D., Proc. natl. Acad. Sci. USA82 (1985) 2478.PubMedGoogle Scholar
  10. 12.
    Lopez de Compadre, R. L., Pearlstein, R. A., Hopfinger, A. J., and Seydel, J. K., J. med. Chem.30 (1987) 900.CrossRefPubMedGoogle Scholar
  11. 13.
    Shallenberger, R. S., and Acree, T. E., Nature216 (1967) 480.PubMedGoogle Scholar
  12. 14.
    Shallenberger, R. S., Acree, T. E., and Lee, C. Y., Nature221 (1969) 555.PubMedGoogle Scholar
  13. 15.
    Deutsch, E. W., and Hansch, C., Nature211 (1966) 75.PubMedGoogle Scholar
  14. 16.
    Kier, L. B., J. pharm. Sci.61 (1972) 1394.PubMedGoogle Scholar
  15. 17.
    Lutz, D., Eder, E., Neudecker, T., and Henschler, D., Mutation Res.93 (1982) 305.Google Scholar
  16. 18.
    Marnett, L. J., Hurd, H. K., Hollstein, M. C., Levin, D. E., Esterbauer, H., and Ames, B. N., Mutation Res.148 (1985) 25.PubMedGoogle Scholar
  17. 19.
    Ciajolo, M. R., Lelj, F., Tancredi, T., Temussi, P. A., and Tuzi, A., J. med. Chem.26 (1983) 1060.CrossRefPubMedGoogle Scholar
  18. 20.
    Shinoda, I., and Okai, H., J. agric. Fd Chem.33 (1985) 792.CrossRefGoogle Scholar

Copyright information

© Birkhäuser Verlag 1988

Authors and Affiliations

  • C. M. Compadre
    • 1
  • R. A. Hussain
    • 1
  • R. L. de Compadre Lopez
    • 1
  • J. M. Pezzuto
    • 1
  • A. D. Kinghorn
    • 1
  1. 1.Department of Medicinal Chemistry and Pharmacognosy, and Program for Collaborative Research in the Pharmaceutical Science, College of PharmacyUniversity of Illinois at ChicagoChicagoUSA

Personalised recommendations