Skip to main content
Proceedings of the National Academy of Sciences of the United States of America logoLink to Proceedings of the National Academy of Sciences of the United States of America
. 1975 Sep;72(9):3355–3358. doi: 10.1073/pnas.72.9.3355

Synthesis and biological properties of a 9,11-azo-prostanoid: highly active biochemical mimic of prostaglandin endoperoxides.

E J Corey, K C Nicolaou, Y Machida, C L Malmsten, B Samuelsson
PMCID: PMC432991  PMID: 1059121

Abstract

The 9,11-azo-prostanoid III [(5Z, 9alpha, 11alpha, 13E, 15S)-9, 11-azo-15-hydroxyprosta-5,13-dienoic acid] has been obtained by synthesis and tested for biological activity in systems which are responsive to the prostaglandin endoperoxides PGH2 (I) and PGG2 (II). The azo analog III is a powerful mimic of these endoperoxides with reference to platelet aggregation and release of serotonin when added to human platelet-rich plasma. The analog III is substantially more active (about 7 fold) than PGG2 in stimulating muscle contraction in the isolated rabbit aorta strip. The very great stability of III relative to PGH2 and PGG2 and its potency as a mimic of these important substances suggest that this azo analog will be of considerable value in future studies of the prostaglandin endoperoxides.

Full text

PDF
3355

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Corey E. J., Mann J. A new stereocontrolled synthesis of prostaglandins via prostaglandin A. J Am Chem Soc. 1973 Oct 3;95(20):6832–6833. doi: 10.1021/ja00801a053. [DOI] [PubMed] [Google Scholar]
  2. Corey E. J., Schaaf T. K., Huber W., Koelliker U., Weinshenker N. M. Total synthesis of prostaglandins F2-alpha and E2 as the naturally occurring forms. J Am Chem Soc. 1970 Jan 28;92(2):397–398. doi: 10.1021/ja00705a609. [DOI] [PubMed] [Google Scholar]
  3. Hamberg M., Hedqvist P., Strandberg K., Svensson J., Samuelsson B. Prostaglandin endoperoxides IV. Effects on smooth muscle. Life Sci. 1975 Feb 1;16(3):451–462. doi: 10.1016/0024-3205(75)90266-0. [DOI] [PubMed] [Google Scholar]
  4. Hamberg M., Samuelsson B. Detection and isolation of an endoperoxide intermediate in prostaglandin biosynthesis. Proc Natl Acad Sci U S A. 1973 Mar;70(3):899–903. doi: 10.1073/pnas.70.3.899. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Hamberg M., Samuelsson B. Prostaglandin endoperoxides. Novel transformations of arachidonic acid in human platelets. Proc Natl Acad Sci U S A. 1974 Sep;71(9):3400–3404. doi: 10.1073/pnas.71.9.3400. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Hamberg M., Svensson J., Samuelsson B. Prostaglandin endoperoxides. A new concept concerning the mode of action and release of prostaglandins. Proc Natl Acad Sci U S A. 1974 Oct;71(10):3824–3828. doi: 10.1073/pnas.71.10.3824. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Hamberg M., Svensson J., Wakabayashi T., Samuelsson B. Isolation and structure of two prostaglandin endoperoxides that cause platelet aggregation. Proc Natl Acad Sci U S A. 1974 Feb;71(2):345–349. doi: 10.1073/pnas.71.2.345. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Malmsten C., Hamberg M., Svensson J., Samuelsson B. Physiological role of an endoperoxide in human platelets: hemostatic defect due to platelet cyclo-oxygenase deficiency. Proc Natl Acad Sci U S A. 1975 Apr;72(4):1446–1450. doi: 10.1073/pnas.72.4.1446. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Nelson N. A. Prostaglandin nomenclature. J Med Chem. 1974 Sep;17(9):911–918. doi: 10.1021/jm00255a001. [DOI] [PubMed] [Google Scholar]
  10. Schneider W. P., Hamilton R. D., Rhuland L. E. Occurrence of esters of (15S)-prostaglandin A 2 and E 2 in coral. J Am Chem Soc. 1972 Mar 22;94(6):2122–2123. doi: 10.1021/ja00761a060. [DOI] [PubMed] [Google Scholar]
  11. Smith J. B., Ingerman C., Kocsis J. J., Silver M. J. Formation of prostaglandins during the aggregation of human blood platelets. J Clin Invest. 1973 Apr;52(4):965–969. doi: 10.1172/JCI107262. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. VANE J. R. THE USE OF ISOLATED ORGANS FOR DETECTING ACTIVE SUBSTANCES IN THE CIRCULATING BLOOD. Br J Pharmacol Chemother. 1964 Oct;23:360–373. doi: 10.1111/j.1476-5381.1964.tb01592.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Weinheimer A. J., Spraggins R. L. The occurrence of two new prostaglandin derivatives (15-epi-PGA2 and its acetate, methyl ester) in the gorgonian Plexaura homomalla chemistry of coelenterates. XV. Tetrahedron Lett. 1969 Dec;(59):5185–5188. doi: 10.1016/s0040-4039(01)88918-8. [DOI] [PubMed] [Google Scholar]

Articles from Proceedings of the National Academy of Sciences of the United States of America are provided here courtesy of National Academy of Sciences

RESOURCES