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.