Synthesis and structure of the platelet aggregation factor thromboxane A2

Abstract

In 1975, Hamberg et al.1 reported evidence for the existence of an unstable platelet-aggregating factor which they named thromboxane A2 (TXA2) and for which they proposed a novel bicyclic oxetane structure (1, below) based on the short half-life of the factor (t1/2(37°C) = 32 s at pH 7.4) and the isolation of degradation products related to thromboxane (TXB2) (2, below). As natural TXA2 has not yet been isolated and characterized as a pure compound, we have synthesized the proposed structure (1) from TXB2 and compared its biological properties with those of authentic, biologically generated material. Here we present evidence that synthetic material having structure (1) is indistinguishable from platelet-derived TXA2 in various biological assays and that the proposed structure (1) for TXA2 is correct.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

References

  1. 1

    Hamberg, M., Svensson, J. & Samuelsson, B. Proc. natn. Acad. Sci. U.S.A. 72, 2994–2998 (1975).

    ADS  CAS  Article  Google Scholar 

  2. 2

    Bhagwat, S. S., Hamann, P. R. & Still, W. C. Tetrahedron Lett. 26, 1955–1958 (1985).

    CAS  Article  Google Scholar 

  3. 3

    Ito, H., Eby, R., Kramer, S. & Schuerch, C. Carbohydr. Res. 86, 193–202 (1980).

    CAS  Article  Google Scholar 

  4. 4

    Varma, A. J. & Schuerch, C. J. org. Chem. 46, 799–803 (1981).

    CAS  Article  Google Scholar 

  5. 5

    Kong, F. & Schuerch, C. Carbohydr. Res. 112, 141–147 (1983).

    CAS  Article  Google Scholar 

  6. 6

    Fried, J., Hallinan, E. A. & Szedo, M. J. J. Am. chem. Soc. 106, 3871–3872 (1984).

    CAS  Article  Google Scholar 

  7. 7

    Mitsunobu, O. Synthesis, 1–28 (1981).

  8. 8

    Krebs, H. A. & Henseleit, K. Hoppe-Seyler's Z. physiol. Chem. 210, 33 (1932).

    CAS  Article  Google Scholar 

  9. 9

    Corey, E. J. & Nicolaou, K. C. J. Am. chem. Soc. 96, 5614–5616 (1974).

    CAS  Article  Google Scholar 

  10. 10

    Corey, E. J. & Clark, D. A. Tetrahedron Lett., 2875–2878 (1979).

  11. 11

    Corey, E. J., Nicolaou, K. C. & Melvin, L. S. J. Am. chem. Soc. 97, 653–654 (1975).

    CAS  Article  Google Scholar 

  12. 12

    Narasaka, K., Maruyama, K. & Mukaiyama, T. Chem. Lett., 885–888 (1978).

    Article  Google Scholar 

  13. 13

    Bundy, G. L. et al. J. med. Chem. 26, 1089–1099 (1983).

    CAS  Article  Google Scholar 

  14. 14

    Mukaiyama, T., Usui, M. & Shimada, E. Chem. Lett., 1045–1048 (1975).

    Article  Google Scholar 

  15. 15

    Weinshenker, N. M., Crosby, G. A. & Wong, J. Y. J. org. Chem. 40, 1966–1971 (1975).

    CAS  Article  Google Scholar 

  16. 16

    Laganis, E. D. & Chenard, B. L. Tetrahedron Lett. 25, 5831–5834 (1984).

    CAS  Article  Google Scholar 

  17. 17

    Needleman, P. et al. Nature 261, 558–560 (1976).

    ADS  CAS  Article  Google Scholar 

  18. 18

    Needleman, P., Minkes, M. & Raz, A. Science 193, 163–165 (1976).

    ADS  CAS  Article  Google Scholar 

  19. 19

    Folco, G., Granstrom, E. & Kindahl, H. FEBS Lett. 82, 321–324 (1977).

    CAS  Article  Google Scholar 

  20. 20

    Smith, J. B., Ingerman, C. & Silver, M. J. clin. Invest. 58, 1119–1122 (1976).

    CAS  Article  Google Scholar 

  21. 21

    Fitzpatrick, F. et al. Biochim. biophys. Acta 573, 238–244 (1979).

    CAS  Article  Google Scholar 

  22. 22

    Piper, P. J. & Vane, J. R. Nature 223, 29–35 (1969).

    ADS  CAS  Article  Google Scholar 

  23. 23

    Vane, J. R. Br. J. Pharmac. 12, 344–349 (1957).

    CAS  Google Scholar 

  24. 24

    Bunting, S., Moncada, S. & Vane, J. R. Br. J. Pharmac. 57, 462 (1976).

    Google Scholar 

  25. 25

    Born, G. V. R. Nature 194, 927–929 (1962).

    ADS  CAS  Article  Google Scholar 

Download references

Author information

Affiliations

Authors

Rights and permissions

Reprints and Permissions

About this article

Cite this article

Bhagwat, S., Hamann, P., Still, W. et al. Synthesis and structure of the platelet aggregation factor thromboxane A2. Nature 315, 511–513 (1985). https://doi.org/10.1038/315511a0

Download citation

Further reading

Comments

By submitting a comment you agree to abide by our Terms and Community Guidelines. If you find something abusive or that does not comply with our terms or guidelines please flag it as inappropriate.