Discovery and synthesis of rioprostil.
Between 1972 and 1979 a research team at Miles Laboratories produced 1200 prostaglandin analogues as potential pharmaceuticals. Most of these analogues were produced using the Sih synthesis. They were screened in several animal models and a few were found to inhibit gastric acid secretion in the rat. The best compound (TR-4698, rioprostil) is being pursued as an anti-ulcer and cytoprotective agent. An improved synthesis of this compound involves the use of n-butyllithium and copper (I) cyanide in a one-pot conjugate addition of a vinyl tin intermediate with a chiral alkylated cyclopentenone. Multihundred gram lots of rioprostil are produced with only one chromatography, that of the final substance, needed.
Kluender
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Miles Laboratories, Inc., Elkhart, Indiana 46514.
Corey
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D000818:Animals; D000897:Anti-Ulcer Agents / Q000138:chemical synthesis / Q000266:history; D049673:History, 20th Century; D006801:Humans; D011458:Prostaglandins E / Q000266:history; D016630:Rioprostil; D013329:Structure-Activity Relationship; D014481:United States
D000897:Anti-Ulcer Agents; D011458:Prostaglandins E; D016630:Rioprostil