Synthesis and Gastrointestinal Pharmacology of a 3E,5Z Diene Analogue of Misoprostol

Article abstract of DOI:10.1021/jm00384a032

A stereospecific synthesis and the gastric antisecretory and diarrheal activity of a 3E,5Z diene analogue of misoprostol are described.The key intermediate in the synthesis was an α chain truncated acetylene that was obtained by a cuprate/enolate capture procedure on the corresponding cyclopentenone.Palladium-catalyzed coupling of the acetylene with methyl 4-iodo-3(E)-butenoate provided the conjugated enyne.Although selected hydrogenation of the enyne with Lindlar catalyst failed, the desired 3E,5Z diene was obtained with P-2 nickel as a catalyst.The diene was about 3 times more potent than misoprostol in inhibiting gastric acid secretion in dogs and also in producing diarrhea in rats.