Total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid via stereoselective C-H insertion and efficient 3,4-stereocontrol.
Reported herein is a novel approach to the total syntheses of (-)-alpha-kainic acid and (+)-alpha-allokainic acid, where the stereochemistries on C(2), C(3), and C(4) of the pyrrolidine core were introduced efficiently and selectively. A regio- and stereoselective C-H insertion reaction was utilized to prepare the gamma-lactam as an intermediate. A Michael-type cyclization of phenylsulfone with a conjugated acetylenic ketone was developed to prepare the tricyclic ketone as a key intermediate for (-)-alpha-kainic acid. Subsequently, a stereoselective dephenylsulfonylation was carried out successfully to secure the cis relationship at C(3) and C(4) centers. An unprecedented acetylation on the phenylsulfone, followed by a stereoselective dephenylsulfonylation, secured the trans relationship at C(3) and C(4) centers in (+)-alpha-allokainic acid.
Loker Hydrocarbon Research Institute and Department of Chemistry, University of Southern California, Los Angeles, California 90089-1062, USA.
Young Chun
YC
Jung
Cheol Hwan
CH
Yoon
Edward
E
Turos
Kyung Soo
KS
Yoo
Kyung Woon
KW
Jung
D003500:Cyclization; D007608:Kainic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry; D008968:Molecular Conformation; D013237:Stereoisomerism
C495695:allokainic acid; D007608:Kainic Acid