Biomedical Engineering Reference
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NHPh
O
O
organocatalysis
R
1
O
+
PhNO
R
1
R
2
R
2
NHPh
NHPh
O
O
Catalyst:
Product:
Me
OH
OH
CO
2
H
Me
N
H
Me
2
125
82%, 99%
ee
(after NaBH
4
reduction)
126
quant., 98%
ee
(after NaBH
4
reduction)
O
O
O
O
PhHN
PhHN
S
Me
Me
127
84%, ee > 99%
128
69%, ee > 99%
SCHEME 6.26
Proline-catalyzed
a
-aminoxylation of aldehydes and ketones.
ketones with nitrosobenzene (PhNO) afforded the corresponding
a
-aminoxycarbonyl
compounds (
125
128
-
) with excellent selectivities. Cleavage of the N-O bond
a
-hydroxyaldehydes
eventually
furnished
the
corresponding
and
ketones
(Scheme 6.26) [48-51].
MacMillan and coworkers constructed the C10-C13 unit of callipeltoside C
(
) [9] using a proline-catalyzed
a
-aminoxylation. Indeed,
a
-aminoxylation of
aldehyde
19
129
in the presence of proline (
2
) produced
a
-aminoxyaldehyde
130
.
Subsequent reduction of the aldehyde moiety and the N-O bond gave diol
in
high yield and excellent enantioselectivity (Scheme 6.27). The latter was then
converted to the corresponding vinyl magnesium bromide
131
132
in order to be
coupled with the aldehyde
21
, thus completing the synthesis of the C1-C14 unit
133
[10].
Fumagillin
was isolated in 1949 from the microbial organism
Aspergillus
fumigatus
and was described as an antimicrobial agent [52] till the early 1990s,
when it was reported to be a potent and selective inhibitor of angiogenesis [53]
(Scheme 6.28).
In 1972, Corey and Snider reported the first total synthesis of fumagillin
134
134
in a racemic form [54]. More recently, Hayashi and coworkers employed the
a
-aminoxylation of ketone
to form the epoxycyclohexane ring in a diastereo-
selective fashion (Scheme 6.28). The bis-TMS ether
135
was then prepared via a
diastereoselective cyanation, while a diastereoselective Michael addition allowed
the introduction of the side chain [55]. Hayashi et al. demonstrated that the
a
-aminoxylation of aldehydes could also be used to control the C3 chiral center of
cytotrienin A (
137
31
) (Scheme 6.7) [12].
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