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OBn
BnO
BnO
H
H
H
MeNH
2
HOAc
Δ
OHC
MeN
MeN
OHC
189
188
187
OBn
OBn
OBn
[1,5]-hydride
shift
H
H
H
H
2
O
H
N
~75%
N
H
HN
192
191
190
O
O
O
steps
H
HN
Secodaphniphylline
193
SCHEME 9.32
Synthesis of secodaphniphylline
193
by Heathcock and coworkers.
The hexahydropyrolo[2,3-
b
]indole alkaloids include an interesting array of
natural products, including amauromine, ardeemins, aszonalenin, flustramines,
roquefortine, and pseudophrynamines among others. The group of Kawasaki has
utilized a domino Wittig-Horner/Claisen reaction to install the required allylic
moiety at the C3a position in the total syntheses of several of these alkaloids.
In one such example, when flustramines and flustramides (both isolated from the
marine bryozoan
F. foliacea
) were targeted, an aryl bromide moiety remained
throughout the synthesis [74]. Treating substrate
with diethyl cyanomethylpho-
sphonate in the presence of
t-
BuOK forms the Wittig-Horner product
194
195
, which
upon warming aromatizes to give compound
. As the last step of the domino
process, a Claisen rearrangement through the allyl vinyl ether moiety creates the C3a
allyl functionality required for the natural product in high ee of 97%. From this
advanced precursor
196
) can be accessed in six
steps (Scheme 9.33). The series of flustramines and flustramides have several modes
of biological activity. Along with the described synthesis, several other natural allyl
indole derivatives have been prepared through a similar route.
197
, the natural product flustramine B (
198
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