Chemistry Reference
In-Depth Information
O
H
H
O
O-Troc
OH
Bz
Bz
NH
O
NH
O
Troc-Cl
10
2
7
2
7
O
O
pyridine
1
O
O-Troc
O
OH
CH
2
Cl
2
H
H
H
O
H
0°C
OAc
OAc
OBz
777
OBz
46 %
Yarovenko
reagent
870
O
OH
Bz
NH
O
10
O
O
OH
H
H
OAc
871
OBz
Oxidation of taxol 777 with Jones' reagent yields 7-oxotaxol 873,2
0
,7-dioxotaxol, or
2
0
-oxo-7-acetyl taxol. In order to selectively obtain 7-oxotaxol, it is necessary to block
the C-2
0
hydroxy function. This is accomplished using the Troc group, introduced
with Troc-Cl, affording 2
0
-O-Troc-taxol 872 in 85% yield [631].
AcO
O
O
AcO
OH
Bz
OH
Bz
NH
O
NH
O
Troc-Cl
2
2
7
O
O
pyridine
1
O
O-Troc
OH
O
CH
2
Cl
2
-23°C
45 min
H
H
85 %
H
O
OAc
H
OAc
OBz
OBz
777
Jones
reagent
872
O
AcO
O
Bz
NH
O
7
O
OH
O
H
H
OAc
873
OBz
Typical procedure. 2
0
-O-(2,2,2-Trichloroethyloxycarbonyl)taxol 872 [631]:
A solution
of taxol 777 (50 mg) in dichloromethane (1.0 mL) and pyridine (0.1 mL) was cooled
to
23
C and treated with Troc-Cl (0.008 mL) over a period of 45 min. Work-up
by standard methods yielded a mixture of 2
0
-O-Troc-taxol 872 (R
f
¼
0.34; EtOAc/
hexane, 1:1) together with small amounts of taxol, R
f
¼
0.11, and a product as-
sumed to be 2
0
,7-bis-Troc-taxol, R
f
0.74. The product was isolated by PTLC with
EtOAc/hexane (1:1) as solvent, yield: 51 mg (85%); FAB-MS: m/z
¼
1028 [MH
þ
],
¼
1780, 1740, 1690, 1675, 1530, 1505, 1390, 1290, 1255 cm
1
.
A similar, more detailed procedure for the preparation of 872 has been elabo-
rated in order to synthesize the tritiated derivative [
3
H]-7-acetyl-taxol [632].
509; IR: n
max
¼
