A new approach to kainoids: Total syntheses of (-)-kainic acid and (+)-allokainic acid

• Main Author: Jung, Young Chun
• Format: Others
• Published: Scholar Commons 2006
• Subjects: C-H insertion; Y-lactam; Dephenylsulfonylation; Rhodium; Boron heck; Palladium; American Studies; Arts and Humanities
• Online Access: http://scholarcommons.usf.edu/etd/2577; http://scholarcommons.usf.edu/cgi/viewcontent.cgi?article=3576&context=etd

(-)-Kainic acid and its C-4 epimer, (+)-allokainic acid are parent members of a class of substituted pyrrolidines known as kainoids. They have been found to exhibit powerful biological properties, principally neuroexcitatory. Kainic acid has become especially important in the study of Alzheimer's disease, epilepsy, and other neurological disorders. The total syntheses of (-)-kainic acid and (+)-allokainic acid were achieved using (L)-glutamic acid as the starting material and the sole source of stereochemical induction. The key steps for these successful syntheses involve formation of the gamma-lactam core via rhodium (II) catalyzed intramolecular C-H insertion of the alpha-diazo-alpha-(phenylsulfonyl)acetamide intermediate and the stereoselective dephenylsufonylation. Pd(II)-catalyzed and oxygen promoted carbon-carbon bond formation methodologies using organoboronic reagents were developed. The first one is a mild and efficient Pd(II) catalysis, leading to the formation of carbon-carbon bonds between a broad spectrum of organoboron compounds and alkenes. Molecular oxygen was employed to reoxidize the resultant Pd(0) species back to Pd(II) during catalytic cycles.This oxygen protocol promoted the desired Pd(II) catalysis, whereas it retarded competing Pd(0) catalytic pathways such as Heck or Suzuki couplings. The second one is the formation of symmetric biaryls and dienes via oxidative dimerization of aryl and alkenyl boronic acids. These conditions utilized Pd(II) catalysts under an oxygen atmosphere with water as the solvent. The use of phase transfer catalysts promoted efficient and mild syntheses of a wide range of materials.