Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigatorMasakatsu Shibasaki
Publication year2002
Synthesis typeTotal
Number of steps 31 (linear)
References
Part 1 of 1
intermediate structure
Dimethyl malonate, KOt-Bu
THF
4 °C to RT, 24 h, 91%
intermediate structure
TsOH, 2-Ethyl-2-methyl-1,3-dioxolane
RT, 16 h
intermediate structure
LiCl
DMSO, H2O
140 °C, 17 h, 97% (2 steps)
intermediate structure + intermediate structure
i-Pr2NLi
THF
-78 °C, 19 h, 72%
"The yield was 82 % brsm."
intermediate structure
NaBH3CN, TiCl4
CH2Cl2, THF
-78 to -55 °C, 10.5 h
intermediate structure
CuCl, DCC
PhH
Reflux, 5 h, 70% (2 steps)
intermediate structure
i-Bu2AlH
CH2Cl2
-78 °C, 60 min
intermediate structure
Et3N, TIPSOTf
CH2Cl2
-78 °C, 10 min, 98% (2 steps)
intermediate structure
Camphorsulfonic acid
Acetone
RT, 2 d, 62%
"The yield was 90 % brsm."
intermediate structure
TMSCl, LiTMP
THF
-78 °C, 2 h
intermediate structure
Pd2(dba)3.CHCl3, Diallyl carbonate
MeCN
RT, 12 h, 90% (2 steps)
intermediate structure
i-Pr2NLi, TMSCl
THF
-78 °C, 2 h
intermediate structure
CH2O, Yb(OTf)3
H2O, THF
RT, 3 d
intermediate structure
DBU
CH2Cl2
RT, 60 min, 57% (3 steps)
intermediate structure
DMAP, I2
CH2Cl2
RT, 5 h, 89%
intermediate structure + intermediate structure
CuI, Pd2(dba)3.CHCl3, Ph3As
DMF
RT, 48 h, 100%
See the Stille Coupling
intermediate structure
i-Pr2NEt, TMS(CH2)2OCH2Cl
CH2Cl2
4 °C to RT, 24 h, 100%
intermediate structure
Et3N.3HF
THF
RT, 2.5 d, 100%
intermediate structure + intermediate structure
i-Pr2NEt, Tf2O
CH2Cl2
-78 °C, 90 min
intermediate structure
NH4Cl, Zn
H2O, MeOH
RT, 2 h, 77% (2 steps)
intermediate structure
Me2SSMe+ BF4-
CH2Cl2
RT, 3 h, 86%
intermediate structure
NaBH3CN, TiCl4
CH2Cl2, THF
-78 °C, 65 min, 68%
intermediate structure
HCl
H2O, MeOH
55 °C, 3 h
intermediate structure
Ac2O
Pyr
RT, 36 h
intermediate structure
NaOMe
MeOH
RT, 30 min
intermediate structure
Imidazole, TIPSCl
CH2Cl2, DMF
4 °C, 2 h, 51% (4 steps)
intermediate structure
NaBH4, NiCl2
EtOH, MeOH
RT, 40 min, 33%
"The yield was 94 % brsm."
intermediate structure
Et3N, Pyr.SO3
DMSO
RT, 60 min
intermediate structure
Et3N.3HF
THF
RT, 12 h, 83% (2 steps)
intermediate structure
NaOMe
MeOH
40 °C, 2 d
intermediate structure
Malonic Acid, NaOAc
Ac2O, AcOH
110 °C, 2 h, 42% (2 steps)
See the Aldol Addition
intermediate structure