Biomedical Engineering Reference
In-Depth Information
OPiv
OPiv
OH
O
O
O
(CH
2
OH)
2
cat.
p-
TsOH
7 steps
O
OMOM
O
Benzene, reflux
O
O
OMe
O
OMe
H
H
(-)
-
142
143
144
MeO
MeO
MeO
H
O
OH
O
O
O
O
OH
H
OH
OH
H
H
O
H
O
O
O
OPiv
OPiv
O
OPiv
147
146
145
MeO
MeO
MeO
3 steps
steps
O
O
O
OPiv
NMe
NMe
H
H
O
H
O
HO
O
O
148
149
(-)-Morphine
150
SCHEME 9.26
Synthesis of morphine
150
by Ogasawara and coworkers.
at reflux forms the hydrophenanthrene
as a single stereoisomer in 50% yield.
The rationale behind this complex transformation is explained through initial
ketal ring opening to
148
144
, which then undergoes a retro-aldol cleavage to give
oxenium ion
. Subsequent electrophilic aromatic substitution and elimination then
affords the domino product
145
148
. Conversion of compound
148
to morphinan
149
,a
known precursor to morphine, constitutes a formal synthesis of morphine (
).
Interestingly, the same strategy has been used to produce the second natural products
(
150
รพ
)-ferruginol [59] and 18-keto-pseudoyohimbane [60].
9.3.3. Nucleophilic Substitutions, 1,2-Additions, or Other
Reactions as the Initiating Step
Stephacidin (
), isolated from the
Aspergillus ochraceus
WC76466 fungus, and
related avrainvillamide (
154
), isolated from a marine fungal strain
Aspergillus
sp.,
belong to a similar class of indole alkaloids, the latter in the
N
-oxide form. This group
of compounds have shown
in vitro
cytotoxic activity against various human tumor cell
lines, as well as displaying a more selective activity against the testosterone-
dependent prostate LNCaP cell line (IC
50
value of 0.06
155
M) [61]. Baran and
coworkers devised an attractive thermal deprotection/cyclization/rearrangement
protocol
m
in the later stages of
their preparation of
these natural products
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