Enantioselective total synthesis of (-)-strychnine using the catalytic asymmetric Michael reaction and tandem cyclization.
The enantioselective total synthesis of (-)-strychnine was accomplished through the use of the highly practical catalytic asymmetric Michael reaction (0.1 mol % of (R)-ALB, more than kilogram scale, without chromatography, 91% yield and >99% ee) as well as a tandem cyclization that simultaneously constructed B- and D-rings (>77% yield). Moreover, newly developed reaction conditions for thionium ion cyclization, NaBH3CN reduction of the imine moiety in the presence of Lewis acid to prevent ring opening reaction, and chemoselective reduction of the thioether (desulfurization) in the presence of exocyclic olefin were pivotal to complete the synthesis. The described chemistry paves the way for the synthesis of more advanced Strychnos alkaloids.
Ohshima
Takashi
T
Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Xu
Youjun
Y
Takita
Ryo
R
Shimizu
Satoshi
S
Zhong
Dafang
D
Shibasaki
Masakatsu
M
D003500:Cyclization; D013237:Stereoisomerism; D013331:Strychnine / Q000138:chemical synthesis*
D013331:Strychnine