Application of Rhodium-Catalyzed Cyclohydrocarbonylation to the Syntheses of Enantiopure Homokainoids.

Kainic acid, rigidified (S)-glutamic acid, is a well-known kainite receptor agonist for the excitatory transmission in the central nerve system. Our interest in highly selective kainite ligands, prompted us to design a series of new kainic homologues, "homokainoids", i.e., conformationally rigidified (S)-glutamic acids. For the syntheses of enantiopure novel homokainoids (pipecolinoglutamic acids), we successfully applied cyclohydrocarbonylation (CHC) reaction that has been developed in these laboratories. Efficient total syntheses of enantiopure novel homokainoids from (R)-serine feature the highly diastereoselective conjugate addition and the regioselective CHC process in the key steps.