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1,3-Dipolar cycloadditions using carbohydrate oximes
175
and
58
or related
structures have also been applied as key steps in the syntheses of complex natural
products. As the isoxazolidine N-O bond is readily cleaved under reductive condi-
tions, these cycloadditions are also useful for the preparation of compounds not
containing isoxazolidine motifs. In an elegant approach Vasella used mannofuran-
ose hydroxylamine in the stereoselective total synthesis of nojirimycin (Scheme
4.32) [46].
O
D-manno
1.)
CO
2
tBu
H
3
C
H
3
C
H
3
C
H
3
C
O
O
O
O
H
H
3
C
CH
3
H
3
C
CH
3
1.) OsO
4
, NMO
2.) FeCl
3
, acetone
178d
20% over 5 steps
HO
N
nojirimycin
O
O
- H
2
O
O
O
O
O
HO
58
CO
2
tBu
CO
2
tBu
HO
2.)
N
O
N
O
OH
OH
O
191
O
O
3
189
190
40% from
58
O
O
H
3
C
CH
3
Scheme 4.32
Asymmetric synthesis of nojirimycin via 1,3-dipolar cycloaddition with
carbohydrate-derived nitrones.
The group of Kibayashi reported an approach for the synthesis of the peptide-
analog natural products (
)-epinegamycin (
199
) using
cyclohexylidene-modified carbohydrate nitrone
194
derived from d-gulonic-
+
)-negamycin (
198
) and (
−
-
lactone
192
(Scheme 4.33) [47]. The 1,3-dipolar cycloaddition of
194
to
N-
Cbz allyl
γ
D-gulo
D-gulonic-
γ
-lactone
O
O
CO
2
Me
3 steps
CO
2
Me
N
NHCbz
O
OH
O
O
N
OH
H
OF
e
195
- H
2
O
OH
OH
O
O
O
O
toluene
OH
O
O
HO
O
O
192
193
194
CbzHN
CbzHN
O
O
N
N
CbzHN
O
O
CbzHN
+
+
CO
2
Me
CO
2
Me
OH
OH
O
O
1.) HCl, MeOH
2.) BnBr, K
2
CO
3
DMF
N
N
O
O
O
O
Bn
Bn
O
O
O
O
94%ee
94%ee
trans-197
cis-197
3.) LiAlH
4
, Et
2
O
50% trans/cis 1:2
trans-196
cis-196
84% combined yield
(-)-epinegamycin
CbzHN
(+)-negamycin
CbzHN
6 steps
OH
NH
2
O
6 steps
OH
NH
2
O
N
O
N
H
2
N
CO
2
H
O
N
H
2
N
CO
2
H
H
N
H
OH
Bn
OH
199
Bn
cis-197
trans-197
198
Scheme 4.33
Asymmetric synthesis of (
+
)-negamycin (
198
) and (
−
)-epinegamycin (
199
) with
carbohydrate nitrone
194
derived from d-gulono-
γ
-lactone (
192
).
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