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ON
O
O
Boc
O
O
Boc
NH
O
OH
NH
O
OH
O
Ph
O
OH
O
OH
HO
H
O
HO
H
BzO
O
BzO
OAc
OAc
47
48
N
O
N
O
Boc
O
O
NH
O
Boc
O
NH
O
N
O
N
O
OH
F
R
HO
H
HO
O
BzO
HO
H
O
BzO
OAc
OAc
49
50a
R=H
50b
R=Me
Cheng et al.
82
conjugated cyclic adenosine monophosphate (cAMP) with 9-OH
in the 7-deoxy-9-(R)-dihydro paclitaxel analog, with the hope that cAMP can be
converted to ATP in vivo to promote tubulin polymerization actions of paclitaxel,
and they found conjugate 51a was more cytotoxic for two to three times, and the
cAMP 2
0
-conjugate 51b exhibited reduced cytotoxicity. They also coupled different
purine and pyrimidine ribosides through a succinyl linker to the 9a-OH in 7-deoxy-
9(R)-dihydropaclitaxel.
83
Those derivatives were generally less active toward all
five human normal tumor cells in the assays, whereas enhancement of cytotoxicity
was also observed for two of these analogs toward Bel-7402 human liver and Eca-
109 human esophagus cancer cells.
A series of 9-deoxy analogues was prepared from 13-acetyl-9(R)-OH-baccatin
III (44) by an Abbott Lab group.
84
They found that the 9-deoxypaclitaxel 52a
R
1
BzO
NHBz
R
2
NHBz
O
O
R
2
Ph
O
Ph
O
OR
1
OH
HO
HO
O
O
AcO
BzO
AcO
BzO
51a
R
1
=H, R
2
= 9α−O−cAMP
51b
R
1
=cAMP, R
2
=O
52a
R
1
=OAc, R
2
=OH
52b
R
1
=OAc, R
2
=H
52c
R
1
=H, R
2
=H
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