Rhodium-catalyzed cyclohydrocarbonylation approach to the syntheses of enantiopure homokainoids.
Homologues of kainic acid, a naturally occurring potent glutamate receptor agonist, were designed based on a rigidified pipecolinoglutamic acid structure and can be regarded as homokainoids for their potential activities in the central nervous system. These novel homokainoids in an enantiomerically pure form were synthesized from enantiopure (R)- and (S)-Garner's aldehyde, featuring (i) the highly diastereoselective addition of alkenylcuprates to the acrylate intermediates and (ii) the Rh-catalyzed cyclohydrocarbonylation of homoallylic amine intermediates to construct the functionalized piperidine moiety in the key steps. For the introduction of a substituent at the 4- or 5-position of pipecolinoglutamic acid, a few different strategies were used, which successfully led to the formation of enantiopure homokainoids.
Chiou
Wen-Hua
WH
Department of Chemistry, State University of New York at Stony Brook, Stony Brook, NY 11794-3400, USA.
Schoenfelder
Angèle
A
Sun
Liang
L
Mann
André
A
Ojima
Iwao
I
D002384:Catalysis; D018360:Crystallography, X-Ray; D003500:Cyclization; D006844:Hydrocarbons, Cyclic / Q000737:chemistry*; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008958:Models, Molecular; D008968:Molecular Conformation; D012238:Rhodium / Q000737:chemistry*; D013237:Stereoisomerism
D006844:Hydrocarbons, Cyclic; D012238:Rhodium; D007608:Kainic Acid