Chemistry Reference
In-Depth Information
and thus the results demonstrate that chemical modifications at C-19 can be made
without significant loss of biological activity.
5.2.3
Modifications of Taxol
Modifications of taxol by manipulation of specific functional groups on the entire
system can be performed by treatment with the appropriate reagents.
10-Deoxytaxol 267 is prepared from taxol 241 in four steps. Dehydration of
the alcohol group at C-10 requires protection of the hydroxy functions at C-2
0
and C-7, which is accomplished with Troc-Cl, affording the corresponding 2,2,2-
trichloroethyl carbonate 266 [193].
H
O
OH
Bz
NH
O
7
2´
O
1
O
OH
H
H
OAc
241
OBz
H
O
O-Troc
Bz
NH
O
Troc-Cl
10
7
2´
O
pyridine
O-Troc
O
CH
2
Cl
2
H
H
O
0°C
OAc
OBz
46 %
Yarovenko
reagent
266
O
OH
Bz
NH
O
10
O
O
OH
H
H
OAc
267
OBz
Oxidation of taxol 241 with Jones' reagent yields 7-oxotaxol, 2
0
,7-dioxotaxol, or 2
0
-
oxo-7-acetyl taxol. In order to selectively obtain 7-oxotaxol 269, it is necessary to
block the C-2
0
hydroxy function of 241, which is accomplished using the Troc
group, introduced with Troc-Cl, to afford 2
0
-O-Troc-taxol 268 [194].
Protection of the amidic nitrogen with di-tert-butyl dicarbonate (Boc
2
O) to afford
272, as part of an e
cient and regioselective method for the N-debenzoylation of
taxol 241 to 10-acetyldocetaxel and to Docetaxel 270, has been reported [195]. Taxol
and its semisynthetic analogue Docetaxel (Taxotere
2
) are among the most impor-
tant new antitumor agents of last decade.
