Synthesis of Strychnine

Structure of Strychnine

C21H22N2O2

Principal investigator	Tohru Fukuyama
Publication year	2004
Synthesis type	Total
Number of steps	29 (3 parts)
References	J. Am. Chem. Soc. 2004, 126, 10246.

Part 1 of 3

intermediate structure

Na2CO3 , CSCl2
NaBH4

H2O, THF

-10 °C, 30 min, 56%

intermediate structure

Imidazole, TBSCl

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%

See the Fukuyama Indole Synthesis

intermediate structure

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Part 2 of 3

intermediate structure

Na

EtOH, NH3

-78 °C

See the Birch Reduction

intermediate structure

NaOMe, HC(OMe)3, AcCl

MeOH

0 °C to RT, 22 h

intermediate structure

NBS

DMSO, H2O

RT, 10 min, 62% (3 steps)

intermediate structure

VinylOAc, Lipase AYS

40 °C, 12 h, 46%

intermediate structure

i-Bu2AlH

CH2Cl2

-78 °C, 5 min, 73%

intermediate structure

NaOMe

MeOH

RT, 5 min

intermediate structure

Imidazole, TBSCl

CH2Cl2

RT, 5 min, 61% (2 steps)

intermediate structure

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Part 3 of 3

intermediate structure

+

intermediate structure

Pd2(dba)3, (2-Furyl)3P

PhMe

RT, 20 min, 86%

See the Tsuji-Trost Reaction

intermediate structure

i-Pr2NEt, MeOCH2Cl

CH2Cl2

RT, 3 h

intermediate structure

LiI, 2,4,6-Collidine

80 °C, 60 min

See the Krapcho Decarboxylation

intermediate structure

DMAP, Boc2O

MeCN

RT, 20 min

intermediate structure

HF, NH4F

DMF, NMP

RT, 19 h, 72% (4 steps)

intermediate structure

DEAD, Ph3P, NsNH2

PhMe

RT, 5 min, 95%

See the Mitsunobu Reaction

intermediate structure

DBU

PhMe

100 °C, 3 h

intermediate structure

HCl

H2O, THF

50 °C, 2.5 h

intermediate structure

Dess-Martin Periodinane

CH2Cl2

0 °C to RT, 35 min, 69% (3 steps)

See the Dess-Martin Oxidation

intermediate structure

TMSOTf, Et3N

CH2Cl2

0 °C, 10 min

intermediate structure

mCPBA, NaHCO3

CH2Cl2, H2O

0 °C, 66% (2 steps)

See the Rubottom Oxidation

intermediate structure

Pb(OAc)4

MeOH, PhH

0 °C, 10 min

See the Criegee Reaction

intermediate structure

Me2S, CF3CO2H, PhSH, Cs2CO3

CH2Cl2

RT to 50 °C, 7.5 h, 84% (2 steps)

See the Pictet-Spengler Reaction

intermediate structure

BF3.OEt2, i-Bu2AlH

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

Ac2O, AcOH

110 °C, 2 h, 42% (4 steps)

See the Aldol Addition

intermediate structure

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