Pure Appl. Chem., 2008, Vol. 80, No. 5, pp. 1019-1024
doi:10.1351/pac200880051019
Application of rhodium-catalyzed cyclohydrocarbonylation to the syntheses of enantiopure homokainoids*
Wen-Hua Chiou, Angèle Schoenfelder1, André Mann1, and Iwao Ojima2
1Faculty of Pharmacy, Université Louis Pasteur Strasbourg, France; 2Department of Chemistry, State University of New York at Stony Brook, Stony Brook, New York, USA
Abstract:
Kainic acid (KA), rigidified (S)-glutamic acid, is a well-known kainite receptor agonist for excitatory transmission in the central nervous system (CNS). Our interest in highly selective kainite ligands prompted us to design a series of new kainic homologs, "homokainoids", i.e., conformationally rigidified (S)-glutamic acids. For the syntheses of enantiopure novel homokainoids (pipecolino-glutamic acids), we successfully applied the cyclohydrocarbonylation (CHC) reaction, which 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.
Keywords: cyclohydrocarbonylation; hydroformylation; kainic acid; pipecolinoglutamates; rhodium-catalyzed; rigidified glutamates.
*Paper based on a presentation at the 14th International Symposium on Organometallic Chemistry Directed Towards Organic Synthesis (OMCOS-14), 2-6 August 2007, Nara, Japan. Other presentations are published in this issue, pp. 807-1194.