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Ph
O
O
Boc
Boc
O
H
N
N
O
H
2
Pd(OH)
2
/
C
Ph
O
O
Ph
N
-H
2
O
+
H
+
O
H
H
55%
92%
Ph
H
O
N
H
O
O
O
CO
2
H
N
H
OO
H
Boc
O
134
138
139
140
141
steps
F
Boc
Cy
3
P
Boc
H
Cl
N
C
N
Ru
O
Cl
B
A
A
Cy
3
P
N
Ph
H
H
H
143
CH
2
Cl
2
,
D
D
O
CO
2
Me
N
O
CO
2
Me
H
N
N
E
E
O
O
Nakadomarine A
144
142
SCHEME 13.31
produced
140
as a single diastereomer in 35% yield (Scheme 13.31) [60].
Hydrogenation of
140
over Pearlman's catalyst gave
141
in 92% yield. Functional
group manipulation and elaboration of the pyrrolidine ring provided
142
, which is
set for a ring-closing metathesis to form ring E. Accordingly, exposing
142
to
Grubbs catalyst
143
produced
144
, containing the A, D, and E rings of nakadomarin
A, in 65% yield.
13.2.5.2. Aziridine Ring Opening DeShong and coworkers developed a
[3
þ
2] dipolar cycloaddition approach to
a
-mannosidase inhibitors related to swain-
sonine [61]. Heating a benzene solution of aziridines
145
and
147
at 165
C for 72 h
produced
148
in 65% yield, presumably through the involvement of azomethine ylide
146
(Scheme 13.32). Reduction of
148
with LiAlH
4
gave
149
in 50% yield, which
showed an IC
50
value of 8 mM against
-mannosidase.
This approach was also applied toward the synthesis of (
a
)-
allo
-kainic
acid [62]. Thermolysis of aziridine
150
in the presence of
151
produced a 1:69
mixture of
152
and
153
, predominating in the latter, in 70% yield (Scheme 13.33).
The relative stereochemistry in
153
corresponds to that found in the natural product.
O
O
O
HO
OH
O
CO
2
Me
OH
CO
2
Me
LiAlH
4
OO
N
N
CO
2
Me
N
N
PhH
147
65%
50%
165°C
OMe
OMe
OMe
OMe
145
146
148
149
SCHEME 13.32
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