Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigatorPhilip Magnus
Publication year1992
Synthesis typeTotal
Number of steps 28 (linear)
References
Part 1 of 1
intermediate structure
ClCO2CH2CCl3
CH2Cl2
RT, 40 h, 79%
"The starting material was made according to: Can. J. Chem. 1964, 42, 489. Also isolated was the unsaturated ester (10 % yield, see next step)."
intermediate structure
NaOMe
MeOH
RT, 30 min, 98%
intermediate structure
NaOH, ClCO2Me, Et3NBn+ Cl-
CH2Cl2, H2O
0 °C, 5 h, 86%
intermediate structure
Zn
AcOH, THF
RT, 10 h, 82%
intermediate structure
Et3N, BOP-Cl, PhSCH2CO2H
CH2Cl2
0 °C, 95 min, 71%
intermediate structure
mCPBA, NaHCO3
CH2Cl2
0 °C, 30 min, 95%
intermediate structure
NaH
THF
0 °C, 105 min, 98%
intermediate structure
(CF3CO)2O, 2,6-Di-tert-butyl-4-methylpyridine
CH2Cl2
RT, 3 h
intermediate structure
CaCO3, HgO
H2O, THF
RT, 12 h
intermediate structure
DBU, Br(CH2)2OH
PhMe
RT, 60 min, 81% (3 steps)
intermediate structure
BH3.THF
THF
RT, 60 min, 100%
intermediate structure
NaHCO3
MeOH
Reflux, 16 h
intermediate structure
Hg(OAc)2
AcOH
RT, 60 h, 43% (2 steps)
intermediate structure
H2SO4, Zn
MeOH
Reflux, 30 min, 88%
intermediate structure
NaOMe
MeOH
Reflux, 2 h, 100%
intermediate structure
DMAP, i-Pr2NEt, 4-Methoxybenzenesulfonyl chloride
CH2Cl2
0 °C to RT, 24 h, 81%
intermediate structure
LiBH4
THF
50 °C, 19 h, 67%
intermediate structure
HClO4
RT, 24 h, 55%
"This product can be obtained from the degradation of natural strychnine and serves as an enantiopure relay."
intermediate structure
DBU, TIPSOTf
CH2Cl2
0 °C to RT, 30 min, 69%
intermediate structure
TMS2NK, (EtO)2P(O)CH2CN
THF
RT, 42 h, 43%
"Also isolated was the Z-isomer (29 % yield) which could be photoisomerized to the desired E-isomer."
intermediate structure
i-Bu2AlH
CH2Cl2
RT, 20 min
intermediate structure
NaBH4
MeOH
RT, 30 min, 31% (2 steps)
intermediate structure
HCl
H2O, MeOH
RT, 15 h, 81%
intermediate structure
DBU, TBSOTf
CH2Cl2
-20 °C, , 60%
intermediate structure
Et3N, Pyr.SO3
DMSO
RT, 4 h, 70%
intermediate structure
Pyr.HF
Pyr
0 °C, 2 h, 60%
intermediate structure
Na.Anthracene
DME
-30 °C to RT, 13.5 h, 90%
intermediate structure
Malonic Acid, NaOAc
Ac2O
Reflux, 2 h, 70%
intermediate structure