Biomedical Engineering Reference
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O
O
NH
NH
N
N
Sulfolane, 240°C
H
H
O
45%
O
Me
N
O
Me
N
O
Boc
Me
Me
H
Me
Me
151
152
O
O
NH
NH
N
N
3
H
H
O
O
Me
Me
N
H
Me
O
O
Me
Me
Me
Me
(+)-Stephacidin A
154
Me
153
CO
2
H
NHCbz
O
NH
N
Boc
O
156
H
Me
Me
O
Me
N
Me
O
Me
O
HN
MeO
2
C
HN
MeO
2
C
Me
CO
2
Me
CO
2
Me
(+)-Avrainvillamide
155
(
S
)
-
157
(
R
)
-
157
SCHEME 9.27
Synthesis of stephacidin
154
and avrainvillamide
155
by Baran and coworkers.
(Scheme 9.27) [62]. Heating
N
-Boc-protected indole
151
in sulfolane first initiated
deprotection to give compound
that then underwent immediate cyclization
through an ene reaction to the proposed spiro compound
152
153
(Scheme 9.27) [63].
From this intermediate
, a 1,2-alkyl shift (ring expansion) furnished the desired
indole alkaloid stephacidin A (
153
). Ingeniously, both enantiomers of stephacidin A
could be accessed in this approach initiated through peptide coupling between acid
156
154
was
prepared in seven steps (12% overall yield) and, furthermore, was used to prepare
(
and either enantiomer of the amine
157
. In this work, the natural product
154
) through oxidation.
The natural antibiotics mycotacins A and B belong to a large family of poly-1,3-
hydroxylated macrocyclic polyene lactones, many of which exhibit antifungal
properties [64]. Early success in the preparation of (
þ
)-avrainvillamide (
155
þ
)-mycotacins A (
166
) and B
(
) was reported by Schreiber and coworkers via the pseudo-
C
2
-symmetric
trisacetonide
167
165
[65]. In an alternative domino-type approach to prepare this
trisacetonide
intermediate, the group of Smith applied reactions involving silyl
dithioacetals and enantiopure epoxides. In this procedure, originally developed by
Tietze et al. [66] for the synthesis of 1,3,5-triols and dihydroxyketones, compound
165
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