Synthesis of Strychnine

C21H22N2O2
Principal investigator | Philip Magnus |
---|---|
Publication year | 1992 |
Synthesis type | Total |
Number of steps | 28 (linear) |
References |
Part 1 of 1

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)."

NaOMe
MeOH
RT, 30 min, 98%


Zn
AcOH, THF
RT, 10 h, 82%

PhSCH2CO2H,
BOP-Cl,
Et3N
CH2Cl2
0 °C, 95 min, 71%

mCPBA,
NaHCO3
CH2Cl2
0 °C, 30 min, 95%



HgO,
CaCO3
H2O, THF
RT, 12 h

Br(CH2)2OH,
DBU
PhMe
RT, 60 min, 81% (3 steps)

BH3.THF
THF
RT, 60 min, 100%

NaHCO3
MeOH
Reflux, 16 h

Hg(OAc)2
AcOH
RT, 60 h, 43% (2 steps)

Zn,
H2SO4
MeOH
Reflux, 30 min, 88%

NaOMe
MeOH
Reflux, 2 h, 100%

4-Methoxybenzenesulfonyl chloride,
i-Pr2NEt,
DMAP
CH2Cl2
0 °C to RT, 24 h, 81%

LiBH4
THF
50 °C, 19 h, 67%

HClO4
RT, 24 h, 55%
"This product can be obtained from the degradation of natural strychnine and serves as an enantiopure relay."

TIPSOTf,
DBU
CH2Cl2
0 °C to RT, 30 min, 69%

TMS2NK,
(EtO)2P(O)CH2CN
THF
RT, 42 h, 43%
See the Horner-Wadsworth-Emmons Reaction
"Also isolated was the Z-isomer (29 % yield) which could be photoisomerized to the desired E-isomer."

i-Bu2AlH
CH2Cl2
RT, 20 min

NaBH4
MeOH
RT, 30 min, 31% (2 steps)

HCl
H2O, MeOH
RT, 15 h, 81%

TBSOTf,
DBU
CH2Cl2
-20 °C, 60%


Pyr.HF
Pyr
0 °C, 2 h, 60%

Na.Anthracene
DME
-30 °C to RT, 13.5 h, 90%

NaOAc,
Malonic Acid
Ac2O
Reflux, 2 h, 70%
