Chemistry Reference
In-Depth Information
Metaferia et al. reported on the synthesis and cytotoxicity of C3
0
-C4 linked
macrocyclic taxoids in 2001. The synthetic strategy was also based on RCM. Simi-
lar to Ojima et al.'s finding, these compounds (100) are less active than paclitaxel in
both cytotoxicity and tubulin assays.
150
However, after careful inspection of the bio-
active conformations of taxoids with computer simulation and nuclear magnetic
resonance (NMR) experiments, they designed several C-4 and C3
0
-Ph ortho-position
linked taxoids (101) that were highly active, several times better than paclitaxel.
151
AcO
AcO
O
O
O
O
OH
OH
HO
HO
O
O
HN
Boc
HO
HO
H
H
O
O
AcO
AcO
O
O
HN
O
O
O
O
O
99b
99a
AcO
AcO
O
O
O
O
OH
OH
HO
HO
O
O
HO
HN
Bz
H
O
HO
H
O
AcO
BzO
O
HN
O
O
X
O
O
100a
X=CH
2
100b
X=OCH
2
99c
AcO
O
O
OH
HO
O
HN
HO
H
Boc
O
BzO
O
X
O
101a
X=OCH
2
, trans
101b
X=CH
2
, cis
3.2.7 Miscellaneous
The conjugate of two molecules with different functions or mechanisms of action
often displayed dual functions or enhanced activities. Based on this rationale,
Shi et al. prepared five taxoid-epipodophyllotoxin dimers. All dimers showed
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