Chemistry Reference
In-Depth Information
A substantially better yield in the coupling step can be achieved using differently
protected coupling partners (N,O-protection with an isopropylidene residue), in
particular (2S)-2-O-3-N-isopropylidene-N-benzoyl-3-phenylisoserine 260, which has
the ''wrong'' configuration at C-2. Coupling of 260 with 7-TES-baccatin III 258 us-
ing DCC/DMAP leads to complete epimerization at C-2 of 260 affording (2
0
R)-2
0
-
O-3
0
-N-isopropylidene-7-TES-taxol 261 in 91% (!) yield [191].
2,2,2-Trichloroethyl chloroformate (Troc-Cl) has been used for the O-protection
of the C-7, C-10, and C-19 positions of 10-deacetyl-19-hydroxybaccatin III 262,a
novel baccatin derivative which is reacted with the N-Boc-3-phenylisoserine 264
in the presence of DCC/DMAP to form, after further steps, the novel 19-hydroxy-
docetaxel 265 [192]. The analogue 265 exhibits a high level of in vitro cytotoxicity
AcO
O
OTES
Bz
N
O
+
H
Ph
OH
3S
O
2S
H
O
260
H
O
OAc
DCC
DMAP
OBz
toluene
reflux
258
AcO
O
OTES
Bz
N
O
Ph
O
3´S
2´R
O
O
H
91 %
261
H
OAc
OBz
O-Troc
OH
O
Troc-O
H
O
O
O-Troc
OH
5 eq.
19
19
OH
10
10
Troc-Cl
7
7
H
H
Boc
N
O
pyridine
20°C, 3 h
1
O
O
264
H
H
H
OAc
H
OAc
OBz
OBz
262
263
DCC DMAP
toluene, 80°C, 2h
OH
H
O
OH
Boc
19
NH
O
O
O
OH
H
H
OAc
OBz
19-hydroxy docetaxel 265
