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AcO
AcO
OH
CHO
OTf
Tf
2
O
AcO
44
AcO
HO
O
HO
O
BzO
AcO
AcO
BzO
53
AcO
R
CHO
NH
O
O
Ph
OH
O
HO
AcO
BzO
54a
R=Bz
54b
R=Boc
Scheme 3-6. Synthesis of B-ring contracted taxoids.
did not affect the in vitro activity at all. Continued deoxygenation at the C-9 and
C-10 positions yield the less-active 7,9-dideoxypaclitaxel 52b and 7,9,10-trideoxy-
paclitaxel 52c within one order of magnitude. The results showed that deoxygena-
tion at these positions may be not of great importance to the cytotoxicity of taxoids.
When 44 was treated with trifluoromethanesulfonic anhydride, a B-ring con-
tracted product was obtained unexpectedly through a plausible Wagner-Meerwein
rearrangement (Scheme 3-6). The initially formed 7-triflate was easily disassociated
to C-7 cation. Subsequent migration of carbon bonds led to the formation of a
B-ring rearranged baccatin 53.
85
The B-ring contracted paclitaxel analog 54a
was about one order of magnitude less active than paclitaxel, whereas the docetaxel
analog 54b was comparable with that of paclitaxel.
When treated with hydrazine, 10-oxo baccatin 55 was transformated into 7,9-
pyrazoline derivatives 56. Cytotoxicities of those C-13 phenylisoserine derivatives
57 were comparable with that of corresponding taxoids, paclitaxel, docetaxel, and
butitaxel.
86
This example is the first successful one in heteroatom substitution at the
C-9 position.
R
2
O
O
O
O
N
NH
N
OH
O
NH
NH
H
HO
R
1
O
H
HO
OH
HO
HO
BzO
O
HO
AcO
BzO
O
O
AcO
BzO
AcO
55
56
57a
R
1
=Ph, R
2
=Bz
57b
R
1
=Ph, R
2
=Boc
57c
R
1
=
i
-Bu, R
2
=Boc
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