MeO
O
NH
MeO
MeO
Colchicine
O
OMe
Since more than 1500 years, colchicine has been used for the
treatment of gout and arthritis. Gout is an illness caused by faulty uric
acid metabolism in which excess uric acid is turned into crystals of
sodium urate, which are then deposited in the joints (most often in the
big toe), causing inflammation and pain. Researchers aren't sure
exactly how colchicine works against gout, but it does seem to reduce
the frequency of severe attacks and relieves residual pain.
- Before Woodward et al.'s synthesis of colchicine (1963),
isothiazoles were unknown.
Me
MeO2C
NH2
S
-H+
Me
MeO2C
Cl
Me
H
N
S-
N
H
H
N
S
MeO2C
Cl
S
MeO2C
Me
+H+
-H+
Me
H
N
3
MeO2C
S
Me
MeO2C
NH2
Me
CSCl2
N
S
Et3N
MeO2C
1. NBS/h!
2. Ph3P
Ph3P
N
S
MeO2C
MeO
1. NaOMe
2. MeO
CHO
MeO
MeO
MeO
MeO
1. LiAlH4
MeO2C
N
S
N2H4, Cu2+, H2O2
MeO
MeO
1. Ph3P=CHCH=CHCO2Me
OHC
MeO
MeO2C
N
S
2. MnO2
MeO
MeO
t
MeO
N
S
2. NaOH
3. I2
MeO
N
S
MeO
MeO
HO2C
HClO4, H2O
MeO
MeO
N
3 S
MeO
B
N2H4/Cu2+/H2O2
HO2C
CO2H
Li
Ph
MeO
MeO
MeO
1.
N
S
2. CO2
3. CH2N2
MeO
MeO
N
S
MeO
MeO
CO2Me
CO2Me
1. NaH
2. AcOH/H2SO4/H2O
N
S
MeO
MeO
C
O
1. EtO2CH/NaH
2. TolSO2S
TolSO2S
+ KOAc
MeO
MeO
MeO
MeO
N
S
Hg(OAc)2
O
AcOH
H2O
HClO4
O
N
S
MeO
MeO
O
SS
Ac2O/Py
N
S
N
S
O
O
AcO- H O
S
SO2Tol
N
S
O
SSO2Tol
AcO-
HS
S
SO2Tol
S
OS SO2Tol
MeO
MeO
N
S
MeO
NaOH/O2
N
S
MeO
MeO
MeO
OAc
O
OAc
OH
N
S
N
S
O-
OH
OH
N
S
OO O
N
S
H
O
O
O
HOO
O
H+
-H+
+H+
MeO
N
S
MeO
MeO
O
OH
1. Ni/NaOH
2. NaBH4
3. Ac2O/Py
MeO
NHAc
H
MeO
MeO
NHAc
1. resolve
H
MeO
MeO
O
OMe
2. CH2N2 and separate
MeO
OH
O