Degradation and isomerization of nileprost, 5-cyano-16-methyl-prostacyclin, in aqueous solution

Nileprost is a new prostacyclin analogue stabilized by introduction of the cyano group at its 5-position. The acidic and alkaline degradation and the structure determination of the degradation products were investigated. The degradation of nileprost is very slow in comparison with that of prostacyclin. Although prostacyclin is easily decomposed to 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) through the hydrolysis of a vinyl ether moiety, nileprost gives little of such hydrolysis product but many isomers and dehydrates. The structures of the products were determined by high-performance liquid chromatography (HPLC), negative ion fast atom bombardment mass spectra (N-FABMS) and nuclear magnetic resonance (NMR) studies. It was found that the vinyl ether moiety of nileprost is converted from 5Z form to 5E form in both media, and that the omega-side chain also undergoes transfer of hydroxyl group or dehydration in acid medium. These results indicate that introduction of the cyano group into the 5-position of prostacyclin is extremely effective for the stabilization of the vinyl ether moiety. Furthermore, on the basis of the structural elucidation, the reaction mechanism of nileprost in both media was clarified.