Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigatorRobert B. Woodward
Publication year1954
Synthesis typeTotal
Number of steps 29 (linear)
References
Part 1 of 1
intermediate structure + intermediate structure
PPA
100 °C, 10 min, 54%
intermediate structure
CH2O, Me2NH, AcOH
Dioxane , H2O
RT, 2 h, 92%
intermediate structure
MeI
PhH
0 °C, 2 h
intermediate structure
NaCN
DMF
Reflux, 60 min, 97% (2 steps)
intermediate structure
LiAlH4
THF
RT to Reflux, 3 h, 85%
intermediate structure
Ethyl glyoxalate
PhH
Reflux, 5 h, 92%
intermediate structure
TsCl
Pyr
RT, 18 h, 64%
intermediate structure
NaBH4
EtOH, H2O
RT, 60 min, 85%
intermediate structure
Ac2O
Pyr
100 °C, 60 min, 99%
intermediate structure
O3
AcOH, H2O
RT, 22 min, 29%
intermediate structure
HCl
MeOH
Reflux, 10 h, 75%
intermediate structure
HI, P (Red)
AcOH, H2O
Reflux, 3.5 h, 72%
intermediate structure
Ac2O
Pyr
RT, 60 min, 94%
intermediate structure
CH2N2
MeOH
RT, 60 min, 84%
intermediate structure
NaOMe
MeOH
Reflux, 20 min, 88%
intermediate structure
TsCl
Pyr
RT, 10 h, 95%
intermediate structure
NaSBn
MeOH
RT, 3 h, 77%
intermediate structure
Ni (Raney)
EtOH
Reflux, 3 h, 84%
intermediate structure
H2, Pd/C
EtOH
RT, 2 min, 73%
intermediate structure
KOH
MeOH, H2O
Reflux, 60 min, 59%
"The yield was 82 % brsm. The enantiomers were resolved by crystallization with (-)-quinine (21 % yield)."
intermediate structure
Ac2O
Pyr
Reflux, 60 min, 42%
intermediate structure
HCl
H2O, AcOH
Reflux, 6 h
intermediate structure
SeO2
EtOH
RT to Reflux, 16 h, 12% (2 steps)
intermediate structure
Sodium acetylide
THF
0 °C to RT, 60 min, 53%
intermediate structure
H2, Lindlar Catalyst
MeOH
RT, 3 min, 86%
intermediate structure
LiAlH4
Et2O, THF
Reflux, , 30%
intermediate structure
HBr, P (Red)
AcOH
120 °C, 3.5 h
intermediate structure
H2SO4
H2O
Reflux, 90 min, 13% (2 steps)
"Also isolated was an oil which, once treated with acetic anhydride and pyridine, afforded a mixture of isostrychnine acetates."
intermediate structure
KOH
EtOH
100 °C, 5 h
"8 mg of strychnine was obtained from a mixture of 7 mg isostrychnine and 65 mg isostrychnine acetates."
intermediate structure