Synthesis of 5,6,7-trinor-4,8-inter-m-phenylene PGI2 and Beraprost

Article abstract of DOI:10.1016/S0040-4020(99)00020-4

We have disclosed a new class of stable PGI₂ analogue, 5,6,7-trinor- 4,8-inter-m-phenylene PGI₂ which has a phenyl ether moiety instead of enol- ether skeleton in PGI₂. The m-phenylene PGI₂ and its derivative (Betaprost) 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.