Chemistry Reference
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DBU and silica gel in 1,2-dichloroethane, respectively.
117
Paclitaxel and docetaxel
analogs with 7a-F are not superior to the parent compounds in both in vitro
and in vivo, and those with 7,19-cyclopropane and 6,7-olefin were comparably
active.
118
HO
xyl
AcO
OH
NHBz
glu
O
NHBoc
O
O
O
O
Ph
O
Ph
O
OH
OH
HO
HO
O
O
BzO
BzO
AcO
AcO
74
75
AcO
AcO
Bz
NHBz
O
O
O
NH
O
R
F
Ph
O
Ph
O
OH
OCO
2
Bn
HO
H
HO
O
BzO
O
AcO
BzO
AcO
76a
R=SMe
76b
R=SCH
2
OMe
77
AcO
AcO
NHBz
NHBz
O
O
O
O
Ph
O
Ph
O
OCO
2
Bn
OCO
2
Bn
HO
HO
O
O
BzO
BzO
AcO
AcO
79
78
In the early 1990s, the Bartons protocol was widely applied to the preparation of
deoxygenated derivatives at many sites on taxanes. Enhancement of cytotoxicity
was observed for many 7-deoxy paclitaxel and docetaxel analogs, along with a
reduction of cytotoxicity for 7,10-dideoxy analogs.
119,120
An efficient synthetic
route of 7-deoxypaclitaxel from taxine, a mixture containing several structurally
related
methylenes,
121
taxanes
with
4(20)-exocyclic
as
well
as
synthesis
of
7-deoxytaxane from
6,7
taxane were also reported.
122
In general, all above-mentioned modifications at C-7 did not change their
activities to a great extent, which indicates that C-7 radicals may not interact
with tubulin binding site significantly. This hypothesis was confirmed by x-ray
crystallography and molecular simulation.
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