Biomedical Engineering Reference
In-Depth Information
Bn
Bn
Bn
NMe
N
N
Bn
CO
2
H
•HCl
Et
3
N
PhMe
reflux
H
Br
Br
CHO
Br
Br
O
+
+
N
Bn
O
N
R
N
O
N
O
Bn
Bn
222a
(R = H)
222b
(R = Bn)
223
(16%)
224
(7%)
225
(51%)
steps
NH
HN
N
HN
RO
2
C
MeO
2
C
N
N
•xHCl
H
NH
2
H
NH
H
N
Martinelline
227a
(R = )
Martinellic acid
227b
(R = H)
NH
2
NH
226
SCHEME 13.45
Snider and coworkers started with the pyrrolidine-substituted benzaldehyde
228
(Scheme 13.46) [84]. Upon heating with
N
-benzyl glycine, azomethine ylide
formation and intramolecular cycloaddition produced
229
in 68% yield, along with
7% of the diastereomer with opposite configurations at C5a and C2a. Reaction of
229
with LiBH
4
resulted in a reductive cleavage of the amide bond to provide
230
in 67%
yield. Several steps were required to convert the side chain alcohol group into an
azide. The sequence began with the protection of the aniline nitrogen as the
trifluoroacetate with subsequent mesylation, displacement with NaN
3
, and removal
of the trifluoroacetate group, giving
231
in 55% yield from
230
. Finally, exposing an
ethanolic acid solution of
231
to Pearlman's catalyst under a hydrogen atmosphere
afforded the pyrroloquinoline
232
in 82% yield.
Bn
Bn
N
N
Bn
CHO
5a
H
CO
2
H
2a
LiBH
4
MeOH/THF
reflux
67%
H
OH
PhMe, reflux
68%
N
N
H
N
O
O
228
229
230
1. TFAA, Et
3
N
2. MsCl, Et
3
N
then NaN
3
3. K
2
CO
3
, MeOH
55%
Bn
HN
N
H
2
, Pd(OH)
2
NH
2
N
3
EtOH
conc. HCl
82%
H
H
232
231
SCHEME 13.46
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