Biomedical Engineering Reference
In-Depth Information
R
2
O
NH
O
O
organocatalysis
+
R
2
+
NH
2
H
R
1
R
1
H
H
R
3
R
3
MeO
Catalyst:
Product:
90%
ee = 98%
syn
:
anti
> 95:5
(after NaBH
4
reduction)
NH
CO
2
H
H
Ph
OH
2
38
Me
SCHEME 6.8
Proline-catalyzed Mannich reaction.
HO
MeO
CO
2
-
Me
O
Me
O
O
R
N
H
OMe
H
NH
3
+
OH
OBz
NHBz
HO
OH
Nikkomycin B (
39
; R = )
N
-terminal amino acid unit
41
N
O
NH
O
CHO
Nikkomycin B
x
(
40
; R =
)
N
NH
O
FIGURE 6.2
Synthetic analysis of nikkomycin B and B
X
.
) are nucleoside peptide antibiotics isolated
from the culture broth of
Streptomyces tendae
(Figure 6.2) [15]. They are potent
chitin synthetase inhibitors and exhibit fungicidal,
Nikkomycins B (
39
) and B
x
(
40
insecticidal, and acaricidal
activities [16]. For the synthesis of nikkomycins
39
and
40
, a stereoselective
preparation of the
N
-terminal amino acid unit
41
containing three contiguous
stereogenic centers was envisioned.
Hayashi and coworkers employed a proline-catalyzed Mannich reaction between
furfural (
33
), the aniline derivative
42
, and propanal (
23
) to afford
b
-aminoaldehyde
43
in a highly enantio- and diastereoselective fashion (Scheme 6.9). Subsequent
installation of the 4-methoxyphenyl moiety followed by oxidation and diastereose-
lective reduction furnished
b
-amino alcohol
in 96% ee and 69% overall yield.
Oxidative removal of the aromatic substituent on the nitrogen atom followed by
cleavage of the furan ring finally afforded the key intermediate
44
41
[17].
6.2.3. Michael Reaction
The conjugate addition of a carbanion to an
a
,
b
-unsaturated carbonyl compound is
one of the most fundamental carbon-carbon bond forming reaction in organic
synthesis [4,18]. The organocatalytic Michael reaction has been widely investigated
and used in the total synthesis of various bioactive molecules with catalysts such
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