Chemistry Reference
In-Depth Information
AcO
AcO
NHBz
O
O
NHBz
O
OH
O
OH
Ph
O
Ph
O
OH
OH
HO
O
HO
O
O
O
O
AcO
O
O
O
O
R
2
F
F
R
1
60a
R
1
=N
3
,
R
2
=Ac
60b
R
1
=N
3
, R
2
=cycloprapane
60c
R
1
=Cl, R
2
=cycloprapane
60d
AcO
NHBz
O
O
OH
Ph
O
OH
HO
O
O
AcO
O
O
61
at these two positions were replaced with nonaromatic groups, for example, cyclo-
hexane, isobutene, and trans-prop-1-ene, more rigid groups seem to be better than
freely rotating ones. However, even the best one in this series, the 2-debenzoyl-2-
isobutenoyl-3
0
-N-debenzoyl-N-isobutenoyl analog 62a,
96
was not superior to SB-T-
1212 (62b).
Chen et al. synthesized C-2-acetoxy-C-4-benzoate, so-called iso-paclitaxel 63.
This compound was totally inactive either in cytotoxicity or in tubulin polymeriza-
tion assays.
97
It is in agreement with previous observations that only small C-4 sub-
stituents were tolerated.
AcO
NHBoc
O
AcO
O
NHBz
O
OH
O
OH
R
1
O
Ph
O
OH
OH
HO
O
HO
R
2
COO
O
AcO
AcO
BzO
62a
R
1
=
i
-butene, R
2
=
i
-Bu
62b
R
1
=
i
-butene, R
2
=Ph
63
Synthesis of a 2a-N substituted analog 2-debenzoyloxy-2a-benzamido docetaxel
analog 65a was realized as the first example in the preparation of 2a-heteroatom
linkages in our laboratory recently. The key step for the synthesis is transformation
of 2a-baccatin 64a to 2a-azido baccatin 64b through a double S
N
2 conversion. The
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