Abstract
The structure of the most recently discovered, biologically highly active prostaglandin, PGI2 or prostacyclin, is correctly predicted on biogenetic grounds, and a general synthesis starting with prostaglandins of the F2alpha series is reported. Starting with the biologically active 13,14-dehydro-PGF2alpha, the synthesis involves formation of a 5-bromo-6,9alpha-epoxy derivative, followed by esterification and dehydrobromination of the methyl ester to form the prostacyclin structure. The stereochemistry at C-5 and C-6 of all reported products is assigned on the basis of experimental findings and mechanistic reasoning. 13,14-Dehydroprostacyclin methyl ester is considerably more stable at pH 7.5 than prostacyclin. It inhibits platelet aggregation induced by a variety of agents and causes an increase in renal blood flow in the dog at nanomolar levels.
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Selected References
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- Chapnick B. M., Paustian P. W., Klainer E., Joiner P. D., Hyman A. L., Kadowitz P. J. Influence of prostaglandins E, A and F on vasoconstrictor responses to norepinephrine, renal nerve stimulation and angiotensin in the feline kidney. J Pharmacol Exp Ther. 1976 Jan;196(1):44–52. [PubMed] [Google Scholar]
- Fried J., Lee M. S., Gaede B., Sih J. C., Yoshikawa Y., McCracken J. A. Chemical and biological studies on 13-dehydroprostaglandins. Adv Prostaglandin Thromboxane Res. 1976;1:183–193. [PubMed] [Google Scholar]
- Fried J., Lin C. H. Synthesis and biological effects of 13-dehydro derivatives of natural prostaglandin F 2 and E 2 and their l5-epi enantiomers. J Med Chem. 1973 Apr;16(4):429–430. doi: 10.1021/jm00262a032. [DOI] [PubMed] [Google Scholar]
- Gryglewski R. J., Bunting S., Moncada S., Flower R. J., Vane J. R. Arterial walls are protected against deposition of platelet thrombi by a substance (prostaglandin X) which they make from prostaglandin endoperoxides. Prostaglandins. 1976 Nov;12(5):685–713. doi: 10.1016/0090-6980(76)90047-2. [DOI] [PubMed] [Google Scholar]
- Hamberg M., Svensson J., Samuelsson B. Thromboxanes: a new group of biologically active compounds derived from prostaglandin endoperoxides. Proc Natl Acad Sci U S A. 1975 Aug;72(8):2994–2998. doi: 10.1073/pnas.72.8.2994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Moncada S., Gryglewski R., Bunting S., Vane J. R. An enzyme isolated from arteries transforms prostaglandin endoperoxides to an unstable substance that inhibits platelet aggregation. Nature. 1976 Oct 21;263(5579):663–665. doi: 10.1038/263663a0. [DOI] [PubMed] [Google Scholar]
- Pace-Asciak C. Letter: Isolation, structure, and biosynthesis of 6-ketoprostaglandin F1 alpha in the rat stomach. J Am Chem Soc. 1976 Apr 14;98(8):2348–2349. doi: 10.1021/ja00424a065. [DOI] [PubMed] [Google Scholar]
- Pace-Asciak C., Wolfe L. S. A novel prostaglandin derivative formed from arachidonic acid by rat stomach homogenates. Biochemistry. 1971 Sep 28;10(20):3657–3664. doi: 10.1021/bi00796a004. [DOI] [PubMed] [Google Scholar]
- Whittaker N., Bunting S., Salmon J., Moncada S., Vane J. R., Johnson R. A., Morton D. R., Kinner J. H., Gorman R. R., McGuire J. C. The chemical structure of prostaglandin X (prostacyclin). Prostaglandins. 1976 Dec;12(6):915–928. doi: 10.1016/0090-6980(76)90126-x. [DOI] [PubMed] [Google Scholar]