Biomedical Engineering Reference
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MeO
OMe
NMe
2
NMe
2
O
OH
OMOM
O
MOMO
MOMO
o
-Xylene, 140°C
O
OH
89%
PMBO
OPMB
OPMB
Me
2
N
O
O
Paniculide A
NMe
2
Ph
OH
Ph
O
Ph
O
NMe
2
MeO OMe
NMe
2
Toluene, reflux, 10 h
84%
O
OMOM
OMOM
OMOM
Br
Aplysin
(ee = 95%)
SCHEME 8.16
Synthesis of paniculide and aplysin.
be attributed to the formation of a highly nucleophilic enolate species just as in the
anionic oxy-Cope rearrangement (see above). Owing to the highly ordered cyclic
transition state, the rearrangement proceeds with a high level of stereocontrol. As a
general trend, when THF is used as the solvent, the (
Z
)-ester enolate is formed
preferentially, thus leading to the (
E
)-silyl ketene acetal. On the other hand, when a
HMPA/THF mixture is used, the (
E
)-ester enolate intermediate is generated, thus
affording the (
Z
)-silyl ketene acetal.
The Ireland-Claisen rearrangement was used in the synthesis of a number of
natural products, such as (
)-breynolide [100], myxalamide A [101], aspidophy-
tine [102], herboxidiene [103], racemic patulolide [104], epothilones B and D [105],
potent toxin atractyligenin [106], (
þ
)-methyl palustramine [107], sphydrofuran [108],
(
)-indolizidine 167B [109],
(
þ
)-iridomyrmecin [110], (
)-fumagillol
[111],
(
)-kendomycin [113]. For the latter, the authors
reported four synthetic approaches, two of which successfully afforded enantiomeri-
cally pure (
þ
)-discodermolide [112], and (
)-kendomycin via a key Ireland-Claisen rearrangement (Scheme 8.18).
MeO
MeO
MeO
NMe
2-Nitrophenol (1.5 equiv)
CH
3
C(OEt)
3
MeO
MeO
CO
2
Et
O
OBn
OBn
140°C (sealed tube), 60 h
80%
HO
OH
OTBS
OTBS
Galanthamine
CH
3
C(OEt)
3
EtCO
2
H (cat.)
Xylenes, reflux
HO
O
CO
2
Et
O
61%
OMe
OMe
OH
Velloziolide
SCHEME 8.17
Synthesis of galanthamine and velloziolide.
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