Synthesis of Strychnine
C21H22N2O2
| Principal investigator | Robert B. Woodward |
|---|---|
| Publication year | 1954 |
| Synthesis type | Total |
| Number of steps | 29 (linear) |
| References |
Part 1 of 1
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MeI
PhH
0 °C, 2 h
NaCN
DMF
Reflux, 60 min, 97% (2 steps)
LiAlH4
THF
RT to Reflux, 3 h, 85%
Ethyl glyoxalate
Dean-Stark
PhH
Reflux, 5 h, 92%
TsCl
Pyr
RT, 18 h, 64%
NaBH4
EtOH, H2O
RT, 60 min, 85%
Ac2O
Pyr
100 °C, 60 min, 99%
O3
AcOH, H2O
RT, 22 min, 29%
HCl
MeOH
Reflux, 10 h, 75%
HI,
P (Red)
AcOH, H2O
Reflux, 3.5 h, 72%
Ac2O
Pyr
RT, 60 min, 94%
CH2N2
MeOH
RT, 60 min, 84%
TsCl
Pyr
RT, 10 h, 95%
Ni (Raney)
EtOH
Reflux, 3 h, 84%
H2,
Pd/C
EtOH
RT, 2 min, 73%
KOH
H2O, MeOH
Reflux, 60 min, 59%
"The yield was 82 % brsm. The enantiomers were resolved by crystallization with (-)-quinine (21 % yield)."
HCl
AcOH, H2O
Reflux, 6 h
SeO2
EtOH
RT to Reflux, 16 h, 12% (2 steps)
Sodium acetylide
THF
0 °C to RT, 60 min, 53%
H2,
Lindlar Catalyst
MeOH
RT, 3 min, 86%
LiAlH4
Et2O, THF
Reflux, 30%
HBr,
P (Red)
AcOH
120 °C, 3.5 h
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."
KOH
EtOH
100 °C, 5 h
See the Michael Addition
"8 mg of strychnine was obtained from a mixture of 7 mg isostrychnine and 65 mg isostrychnine acetates."