Biomedical Engineering Reference
In-Depth Information
13.2.6.2. Alkaloid Synthesis Using Aziridine Ring-Opening Reactions
The Weinreb and Heathcock groups simultaneously developed related approaches
to the marine alkaloids sarain A. In Weinreb's model studies, pyrolysis of
262
at
320
C gave
264
in 73% yield via the azomethine ylide intermediate
263
(Scheme 13.51) [94,95]. Functional group manipulation and conversion of the
pyrrolidine side chain into an allyl silane provided intermediate
265
, which is poised
for cyclization to the sarain core. Subsequent DIBAL-H reduction and exposure to
FeCl
3
effected the desired cyclization to afford
266
in 57% yield from
265
.
Continued development of the azomethine ylide cycloaddition route employed
aziridine
267
to access bicycle
268
in 78% yield [96]. This approach simplifies the
sequence of reactions used to append the allyl silane moiety (Scheme 13.52). An
enolate anion derived from the amide group was used to provide a functional handle
that could be leveraged for constructing the “eastern” ring. The result of these efforts
was the formation of tricycle
269
[97]. As before, reduction of the lactam carbonyl
Bn
O
O
Bn
Cl
O
Bn
H
N
N
Bn
Bn
Bn
N
N
N
N
Cl
73%
320°C
H
262
263
264
OBn
OBn
OBn
steps
CHO
O
Bn
N
H
H
Ts
N
N
Bn
1. DIBAL-H
N
OH
N
Ts
N
2. FeCl
3
HO
H
57%
Sarain A
TMS
266
265
SCHEME 13.51
O
Bn
TMS
Cl
H
Bn
Bn
O
N
O
N
N
steps
O
N
Bn
Cl
325°C
78%
Ts
N
OMe
N
O
OMe
H
OMe
OMe
OMe
267
268
269
1. DIBAL-H
2. FeCl
3
56%
OMOM
CHO
H
O
O
NH
O
N
steps
N
steps
Ts
N
N
N
O
O
O
O
O
OMe
OTBS
272
271
270
O
SCHEME 13.52
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