Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigatorTohru Fukuyama
Publication year2004
Synthesis typeTotal
Number of steps 29 (3 parts)
References
Part 1 of 3
intermediate structure
CSCl2, Na2CO3
THF, H2O
-10 °C, 30 min, 56%
intermediate structure
TBSCl, Imidazole
CH2Cl2
RT, 5 min, 98%
intermediate structure
Dimethyl malonate, NaH
THF
0 °C to RT, 100 min, 71%
intermediate structure
n-Bu3SnH, Et3B
PhMe
RT, 10 min, 52%
intermediate structure
Part 2 of 3
intermediate structure
Na
NH3, EtOH
-78 °C
See the Birch Reduction
intermediate structure
AcCl, HC(OMe)3, NaOMe
MeOH
0 °C to RT, 22 h
intermediate structure
NBS
DMSO, H2O
RT, 10 min, 62% (3 steps)
intermediate structure
Lipase AYS, VinylOAc
40 °C, 12 h, 46%
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C, 5 min, 73%
intermediate structure
NaOMe
MeOH
RT, 5 min
intermediate structure
TBSCl, Imidazole
CH2Cl2
RT, 5 min, 61% (2 steps)
intermediate structure
Part 3 of 3
intermediate structure + intermediate structure
Pd2(dba)3, (2-Furyl)3P
PhMe
RT, 20 min, 86%
intermediate structure
MeOCH2Cl, i-Pr2NEt
CH2Cl2
RT, 3 h
intermediate structure
LiI, 2,4,6-Collidine
80 °C, 60 min
intermediate structure
Boc2O, DMAP
MeCN
RT, 20 min
intermediate structure
HF, NH4F
DMF, NMP
RT, 19 h, 72% (4 steps)
intermediate structure
NsNH2, Ph3P, DEAD
PhMe
RT, 5 min, 95%
intermediate structure
DBU
PhMe
100 °C, 3 h
intermediate structure
HCl
THF, H2O
50 °C, 2.5 h
intermediate structure
Dess-Martin Periodinane
CH2Cl2
0 °C to RT, 35 min, 69% (3 steps)
intermediate structure
TMSOTf, Et3N
CH2Cl2
0 °C, 10 min
intermediate structure
mCPBA, NaHCO3
CH2Cl2, H2O
0 °C, , 66% (2 steps)
intermediate structure
Pb(OAc)4
MeOH, PhH
0 °C, 10 min
intermediate structure
PhSH, Cs2CO3, Me2S, CF3CO2H
CH2Cl2
RT to 50 °C, 7.5 h, 84% (2 steps)
intermediate structure
i-Bu2AlH, BF3.OEt2
CH2Cl2
-78 °C, 70 min, 93%
intermediate structure
NaBH3CN
AcOH
10 °C, 60 min
intermediate structure
NaOMe
MeOH
RT, 7.5 h
intermediate structure
i-Bu2AlH
CH2Cl2
-98 °C
intermediate structure
Malonic Acid, NaOAc
AcOH, Ac2O
110 °C, 2 h, 42% (4 steps)
See the Aldol Addition
intermediate structure