Biomedical Engineering Reference
In-Depth Information
NC
NC
O
(EtO)
2
P
O
CN
Br
Br
Br
( )
5
( )
5
( )
5
t-
BuOK, DMF
-78°C to rt
88%
O
O
O
N
Ac
N
Ac
N
Ac
194
195
196
OH
( )
5
steps
O
CN
Br
Br
NMe
NMe
O
N
H
N
H
N
H
H
H
(-)-Flustramide B
198
(-)-Pseudophrynaminol
199
197
SCHEME 9.33
Synthesis of flustramide B
198
by Kawasaki and coworkers.
) is a fungal
metabolite with a complex bridged carbocyclic core. This compound has been
reported to inhibit squalene synthase and hence has cholesterol-lowering properties,
and it also inhibits farnesyl transferase. A total synthesis of this natural product
based on earlier domino methodology work involving a triple domino process
was conceived by Shair and coworkers [75]. In this work, the ester
The natural antibiotic (
þ
)-CP-263114 (phomoidride B,
205
200
was treated
with the Grignard reagent
(Scheme 9.34).
This latter intermediate then underwent an anionic oxy-Cope rearrangement to
give the expected nine-membered ring
201
to afford unconjugated diene
202
containing two new stereogenic centers.
Finally, a transannular Dieckmann cyclization afforded the bridged ketone species
204
203
205
, which is the core of the natural product of CP-263114 (
).
O
O
O
O
MOMO
Toluene (0.01 M)
-78°C to rt
53%
C
5
H
9
O
MOMO
5
MeO
O
+
C
8
H
15
BrMg
CO
2
Me
OPMB
BrMgO
OPMB
200
201
202
O
O
O
O
H
( )
2
MOMO
O
O
O
C
5
H
9
O
( )
2
O
steps
MeO
O
OMOM
H
O
O
O
( )
5
C
8
H
15
( )
5
O
BrMgO
CO
2
H
OPMB
OPMB
(+)-CP-263114
205
204
203
SCHEME 9.34
Synthesis of (+)-CP-263114
205
by Shair and coworkers.
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