Abstract
Just after the discovery of PGI2, we started to find chemically and metabolically stable PGI2 derivatives with longer duration of action. Extensive studies led us to a new class of stable PGI2 analogue, 5, 6, 7-trinor-4, 8-inter-m-phenylenePGI2 that has a phenol moiety instead of enol-ether linkage in PGI2. In order to accomplish synthesis of the m-phenylenePGI2, novel synthetic methods were developed, for instance, ortho-selective metal-halogen exchange reaction of bromoanisoles by means of Grignard reagent, copper-catalyzed SN2' cyclization to prepare dihydrocyclopenta [b] benzofuran, and regioselective and stereo-selective elongation of ω-side chain by Prins reaction. Further efforts were devoted to synthesize derivatives of m-phenylenePGI2 with enhanced pharmacological activity and less adverse reaction. Finally, we attained to Beraprost sodium which is the first launched drug as an orally active PGI2. This paper will focus on the study of total syntheses of m-phenylenePGI2.
