Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigatorMartin E. Kuehne
Publication year1993
Synthesis typeTotal
Number of steps 19 (linear)
References
Part 1 of 1
intermediate structure
BnBr, K2CO3
MeOH
Reflux, 3 d, 89%
intermediate structure
Et3N, t-BuOCl
THF
-78 °C, 2.5 h
intermediate structure + intermediate structure
THF
-78 °C to RT, 13 h, 83% (2 steps)
intermediate structure
LiCl, Et3N.HCl
DMA
130 °C, 2.5 h, 84%
intermediate structure
H2, Pd/C
AcOH
RT, , 87%
intermediate structure + intermediate structure
BF3.OEt2
PhMe
Reflux, 18 h
intermediate structure
HClO4
H2O, THF
0 °C to RT, 5 h, 51% (2 steps)
intermediate structure
n-BuLi, Me3S+ I-
THF
-20 °C to RT, 4 h, 70%
intermediate structure
  1. DBU
  2. H2
  3. Pd/C
MeOH
RT to Reflux, 12 h, 70% (2 steps)
intermediate structure
NaBH3CN
AcOH
RT, 30 min
intermediate structure
Ac2O
Pyr
RT, 10 h, 83% (2 steps)
intermediate structure
TMS2NLi
THF
Reflux, 30 min
intermediate structure
NaBH4
AcOH, MeOH
0 °C, 60 min, 64% (2 steps)
intermediate structure
Ac2O
Pyr
RT, ON, 98%
intermediate structure
DBU
Dioxane , H2O
Reflux, 10 h, 61%
intermediate structure
(COCl)2, DMSO, Et3N
CH2Cl2
-78 °C to RT, 2 h, 98%
See the Swern Oxidation
intermediate structure
TMS2NK, (EtO)2P(O)CH2CO2Me
THF
RT, 2.5 h, 39%
"Also isolated was the Z-isomer (42 % yield) which could be photoisomerized to the desired product."
intermediate structure
BF3.OEt2, i-Bu2AlH
CH2Cl2
-78 °C, 4.5 h, 87%
intermediate structure
KOH
EtOH
Reflux, 6 h, 28%
"The yield was 72 % brsm."
intermediate structure