SYNTHESIS OF 5,6,7-TRINOR-4,8-INTER-M-PHENYLENE PGI2 AND BERAPROST

Abstract We have disclosed a new class of stable PGI 2 analogue, 5,6,7-trinor-4,8-inter- m -phenylene PGI 2 which has a phenyl ether moiety instead of enol-ether skeleton in PGI 2 . The m -phenylene PGI 2 and its derivative (Beraprost) were synthesized via dihydrocyclopenta[ b ]benzofuran derivatives as key intermediates by ortho -selective metal-halogen exchange reaction with Grignard reagents and subsequent copper-catalyzed cyclization. The ω-side chains were introduced by stereoselective epoxide formation or Prins reaction.