Chemistry Reference
In-Depth Information
Stereoselective construction of the taxane BC substructure requires an intermedi-
ate isocyano function in 256. Intermediate 256 is obtained in 100% yield by dehy-
dration of the formamide 255 with mesyl chloride [189].
O
NHCHO
O
NC
Ms-Cl
pyridine
rt, 4 h
O
O
100 %
256
255
5.2.2
Semisynthetic Approaches
Some approaches for the semisynthesis of taxol are based on relatively economi-
cally priced 10-deacetylbaccatin III, obtained from leaves of the European yew Taxus
baccata. The leaves are able to regenerate by growing again, whereas removal of the
bark of the Pacific yew Taxus brevifolia, which contains taxol, kills the tree. The
semisyntheses of Denis and Greene from 1988 [190] and 1994 [191] are discussed
here. 10-Deacetylbaccatin III 257 is first protected at the 7-position with a triethyl-
silyl residue and acetylated at the 10-position with acetyl chloride. The resulting
7-TES-baccatin III 258 is coupled with O-protected N-benzoyl-3-phenylisoserine
using a sixfold excess of dipyridyl carbonate (DPC) to afford 2
0
-O-ethoxyethyl-7-
TES-taxol 259, which is deprotected with 0.5% hydrochloric acid to afford taxol
241 [190].
1. TES-Cl
pyridine
20 h
AcO
O
H
O
OTES
OH
H
H
2. Ac-Cl
pyridine
0°C, 48 h
O
O
H
H
H
H
OAc
OAc
OBz
OBz
258
7-TES-Baccatin III
74 %
257
10-Deacetylbaccatin III
Bz
NH
O
6
DPC
2 DMAP
toluene
73°C, 100 h
6
Ph
OH
O
O
0.5 % HCl
EtOH / H
2
O
0°C, 30 h
AcO
O
OTES
Bz
89 %
NH
Taxol
241
Ph
O
O
O
H
40 %
H
OAc
OBz
259
2´-O-Ethoxyethyl-7-O-TES-taxol
