Biomedical Engineering Reference
In-Depth Information
Me
S
H
CO
2
Et
S
H
S
CSA (10 mol%)
Xylene, heat
68%
N
S
N
O
N
H
Me
EtO
2
C
H
238
239
AB
OH
N
D
H
C
N
Me
S
S
A
H
H
CO
2
Et •HCl
B
E
N
N
Boc
Boc
S
C
S
i-
Pr
2
NEt, PhMe
reflux
52%
H
N
O
Me
Manzamine A
EtO
2
C
240
241
CO
2
Et
H
H
H
H
Pd(dba)
2
, dppb
OMe
OMe
OMe
N
N
N
CO
2
H
PhMe, reflux
43%
Boc
Boc
Boc
OMe
OMe
OMe
H
N
NH
SH
O
EtO
2
C
86%
EtO
2
C
242
243
244
COCl
3
79%
245
NaOH
N
N
Mes
Mes
Cl
H
H
H
Ru
Cy
3
P
Cl
Ph
A
B
OMe
OMe
OMe
1. NaBH
4
, CaCl
2
N
N
N
1.
248
2. PPTS
Acetone/H
2
O
Boc
Boc
Boc
OMe
OMe
OMe
2. TPAP, NMO
3. MePPh
3
KHMDS
C
O
O
O
N
N
N
H
E
EtO
2
C
75%
52%
249
247
246
SCHEME 13.48
The Coldham group also targeted the synthesis of indole alkaloids for appli-
cation of the intramolecular dipolar cycloadditions [90]. For example, condensation
of
250
with
N
-allyl glycine in toluene at reflux temperature produced
251
in 42%yield
(Scheme 13.49). Palladium-mediated cleavage of the
N
-allyl group gave
252
(40%
yield), which corresponds to an intermediate in the synthesis of deethylibophyllidine.
The cycloaddition was examined using several amines [91]. Notably, proline reacted
with
253
in dioxane at 110
Ctogive
254
as a 1/1 mixture of diastereomers in
68% yield.
Coldham and coworkers also examined a route to several
aspidosperma
alkaloids, beginning with a cascade sequence similar to theone reported by Pearson
et al. (
cf
Scheme 13.39). In these syntheses,
255
was treated with glycine to give
amine
256
in 79% yield (Scheme 13.50) [92]. Hydrolysis of the ketal group furnished
ketone
257
in 89%yield, whichwas converted into aspidospermidine, aspidospermine,
and quebrachamine through Fischer indole syntheses. These syntheses spurred further
investigation into the scope of the cyclization cascade, and it was found that the acid-
catalyzed condensation of
258a
with glycine ethyl ester followed by intramolecular
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