An improved method for the preparation of N-unsubstituted 1,4,5,6-tetrahydrocyclopenta[b]pyrroles: Synthesis of an azaprostacyclin analogue and its 7-cyano derivative

Article abstract of DOI:10.1055/s-1996-4388

Paal-Knorr cyclization of 2-acetonylcyclopentanone derivatives can be carried out most efficiently by reaction with hexamethyldisilazane (HMDS) when the reagents are previously adsorbed on alumina. By this procedure, the unstable pyrroloprostacyclin derivative rac-6a has been synthesized in 66% yield from racemic 6-oxoprostaglandin E₁ (rac)-5b. In order to obtain less sensitive pyrroloprostacyclin derivatives, rac-6a has been transformed into the stable nitriles rac-7a and rac-7b by cyanation of the pyrrole ring with chlorosulfonyl isocyanate in the presence of triethylamine and subsequent cleavage of the protecting groups, respectively.