Biomedical Engineering Reference
In-Depth Information
O
O
Cl
Cl
Br
Br
N
N
NH
O
N
CuI,
L11
, Cs
2
CO
3
THF, 50-70°C
Br
Br
I
O
N
BOM
BOM
R
R
P
P
Br
Br
P = Boc, Me, BOM
R = H, C(Me)
2
CO
2
Me
23-91%
64
65
66
Cl
Cl
Cl
O
O
BOM
N
O
BOM
N
BOM
N
CuI,
L11
, Cs
2
CO
3
THF, 50°C
O
N
Br
N
NH
N
I
I
N
N
R
N
R
R
R = C(Me)
2
CO
2
Me
67
68
69
(47%)
70
(10%)
O
O
CuI,
L11
, Cs
2
CO
3
THF, 70°C
46%
I
NH
N
Cl
O
O
O
O
Cl
71
72
Cu
O
Cu
O
Br
Cl
Br
N
Y
N
N
X
N
Br
H
N
Br
N
X
Br
Me
Me
Me
O
Br
H
Chartelline A; X = Y = Br
Chartelline B; X = H, Y = Br
Chartelline C; X = Y = H
Chartellamide A; X = H
Chartellamide B; X = Br
Cu
N
N
NH
2
O
NH
2
N
SMe
N
H
CuI,
L11
Cs
2
CO
3
THF, 70°C
92%
HN
N
BOM
7 steps
O
SMe
HN
I
BOMN
BOM
BOMN
Br
Br
Br
Br
Br
Br
73
74
75
Ageladine A
SCHEME 3.27
Model studies toward chartellines and chartellamide and total synthesis of
ageladine A.
group used a similar method for the successful preparation of the zinc matrix
metalloproteinase inhibitor ageladine A by coupling an imidazole containing an
iodo vinylic core
[64].
The number of total syntheses in which copper-mediated enamide formation
has been employed is quite impressive. Besides the examples shown above, some
examples are shown in Scheme 3.28.
In 2001, F
73
and a pyrrole containing an amide group
74
urstner and coworkers used a CuTC-catalyzed cross-coupling in the
final steps of the total synthesis of two cytotoxic marine natural products salicyli-
halamides A and B [65]. Although Cs
2
CO
3
used as the base usually gives very good
results in other studies, it was inefficient in this case. Moving from Cs
2
CO
3
to
rubidium carbonate (Rb
2
CO
3
) proved judicious. The groups of Nicolaou [66] and
Panek [67] have adapted this protocol to prepare apicularen A, a novel natural
antiangiogenic polyketide with potent antitumor activity, via the construction of its
highly unsaturated enamide side chain.
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