(–)-Kainic acid (TKGP-120317) T. Fukuyama, H.

Tokuyama1)

Me CO2H
H H

N CO2H
H H

Activity Neuroexcitory activity（神経興奮作用）

(A) Reformatsky-type reaction, (B) Mitsunobu reaction,

Key Reactions
(C) elimination-Michael addition protocol

TBSO TBSO CO2t-Bu CbzCl TBSO CO2t-Bu

H H ? H H ? H H ?
OAc
Me Me Me
NH THF NH THF NCbz EtOH
O 0 °C to rt O –78 °C to rt O 0 °C

(A)

H
N
Me OTBS Ns Me OTBS H ?, K2CO3;
Me O O
CO2t-Bu CO2Me Ns CO2t-Bu TFA ?, DMAP
N Ns
HO N
?, ? CH2Cl2 DMF
NHCbz CO2Me NHCbz H
toluene, 70 °C 0 °C to rt CO2Me NHCbz
C-002
(B)

LHMDS
H CbzCl TPAP
Me O O
–60 °C to rt; Et3N NMO
Boc
N
LHMDS MeOH CH2Cl2
H
CO2Me NHCbz –60 °C
C-035
(C)

?
O
?, TiCl4 1) aq KOH
Me CO2Me Me CO2Me Me CO2H
cat PbCl2 MeOH
H H H H H H
THF 2) ?
N HCO2Me N HCO2Me CH2Cl2 N H
CO2H
Boc Boc H

(–)-Kainic acid

Reference:
1) H. Sakaguchi, H. Tokuyama, T. Fukuyama., Org. Lett., 10, 1711 (2008)