Biomedical Engineering Reference
In-Depth Information
HO
OH
Pd(OAc)
2
BINAP
Cs
2
CO
3
PhMe, 100°C
62%
OMe
CO
2
Me
CO
2
Me
Me
Me
OMe
5 steps
N
H
Me
HO
Br
OTf
H
Me
NH
2
OMe
OMe
Br
18
19
20
Carbazomadurin A
Me
Me
SCHEME 3.9
Carbazomadurin A synthesis by Knolker and Knoll.
The first total synthesis of carbazomadurin A, a neuronal cell protecting
carbazole alkaloid, was accomplished for the first time in 2003 by Kn
olker and
€
Kn
oll [25]. Among the key steps, the Buchwald-Hartwig aminationwas shown to be a
versatile method for building
N,N
0
-diarylamine
€
20
from arylamine
18
and aryl triflate
19
in 62% yield (Scheme 3.9). A similar reaction was used a few years later by
S
anchen for the total synthesis of the free radical scavenger lipocar-
bazoles A4, A3, and A2 [26].
Chida provided a straightforward way to synthesize nucleoside antibiotics
possessing novel
N
-glycoside structures via
N
-arylation of sugar amines with
heteroaryl halides (Scheme 3.10) [27]. It is worth mentioning that a good yield of
65% was obtained in the presence of a sensitive and highly functionalized sugar.
Enantioselective syntheses of RWJ444772, a promising male erectile dys-
function (MED) phosphodiesterase 5 (PDE5) inhibitor, were reported by Mark
ussmuth and H
€
€
o and
coworkers [28] and Santos and Shankaraiah [29]. Both groups took advantage of
Pd-catalyzed
N
-arylation of the secondary amine
in
the final step of the synthesis (Scheme 3.11). Whereas classical reaction conditions
(e.g., Pd
2
(dba)
3
, BINAP,
t-
BuONa in tetrahydrofuran (THF)) were used byMarko and
coworkers, a novel approach based on cheaper Pd source, ligand-free catalytic
system, and microwave irradiation was proposed by Santos and Shankaraiah (e.g.,
PdCl
2
, 1-butyl-3-methylimidazolium hexafluorophosphate,
24
with 2-bromopyridine
25
[bmin]PF
6
,K
2
CO
3
,
microwave irradiation (MW) (180
C) in dioxane).
NSEM
Pd
2
(dba)
3
(+)-BINAP
t-
BuONa
PhMe, 130°C
65%
N
N
AcO
SEM
AcO
N
BnO
N
3 steps
N
N
BnO
O
SPM VIII
NH
2
N
3
N
N
NH
O
H
OBn
N
3
OBn
Cl
H
OBn
OBn
21
22
23
H
N
N
OMe
CN
HO
N
OH
N
N
OH
HO
O
O
H
N
O
NH
O
MeO
N
H
O
N
N
HO
HO
H
Me(CH
2
)
10
N
H
H
OH
OH
OH
OH
O
SPM VIII
Dapiramicin B
SCHEME 3.10
Synthesis of novel
N
-glycoside structures via Buchwald-Hartwig
N
-
arylation by Chida and coworkers.
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