Biomedical Engineering Reference
In-Depth Information
9.5. PERICYCLIC REACTIONS
In 2009, Porco and coworkers developed an enantioselective method for the con-
struction of the bicyclo[2.2.2]oxetane skeleton found in (
þ
)-chamaecypanone C
(
) [112]. The natural product isolated from the heartwood of
Chamaecyparis
obtusa
var.
formosana
has been shown to be cytotoxic to several human cancer cell
lines. The construction of the carbocyclic core of this natural product was carried out
through a domino retro-Diels-Alder/Diels-Alder reaction starting from compound
287
289
, which was also proposed as an intermediate in the biosynthesis of
289
.
Preparation of
287
was carried out through an initial asymmetric
-ketol rearrange-
a
ment of 4-alkyl-2,4-cyclohexadienone
285
obtained from
284
, which was mediated
by a (
)-sparteine peroxo-copper (II) catalyst (Scheme 9.49) [113]. In this reaction,
an initial [4
. Upon heating, the latter
underwent a retro-Diels-Alder cycloaddition to afford diene
þ
2]-dimerization process led to compound
287
286
, which was sub-
sequently trapped with the reactive cyclopentadienone
288
present in the reaction
mixture, thus affording the natural product (
). Interest-
ingly, further biological studies indicated a tubulin polymerization inhibition to be
the mode of action of
)-chamaecypanone C (
289
.
Overman and Deng used a [3
289
þ
3]-sigmatropic rearrangement in a domino
process for their synthesis of antifungal antibiotic (
294
)-preussin (
). In this example,
(
S
)-phenylalanine was first converted to amine
as the precursor for the domino
reaction [114]. Following a reaction with decanal to form imine
290
, an aza-Cope
rearrangement generated the second intermediate
292
. Subsequent Mannich reaction
afforded acylpyrrolidine
291
293
, which was then taken through to the natural product as a
single enantiomer
294
in 11 steps and 8% overall yield (Scheme 9.50).
Carre
no and coworkers completed the enantioselective synthesis of
~
(
) using a Diels-Alder reaction/pyrolytic sulfoxide elimination
process. The natural product, initially isolated from the roots of
Inula royleana
DC,
has been used in the Himalayan region as an insecticide and disinfectant. It has also
þ
)-royleanone (
300
Cu(CH
3
CN)
4
PF
6
(-)-Sparteine, LiOH·H
2
O
OH
O
OH
OH
EtOH, Toluene, 3 Å MS
O
2
, THF, -78°C, 16 h
O
284
285
286
Benzene
reflux, 12 h
47%
O
1.
288
, DDQ
o
-Dichlorobenzene
150°C, 1 h
2. BBr
3
, CH
2
Cl
2
-78°C to rt
OH
OH
OH
H
OH
O
H
OMe
O
O
OH
O
H
288
OH
286
287
(+)-Chamaecypanone C
289
O
OMe
SCHEME 9.49
Synthesis of chamaecypanone C
289
by Porco and coworkers.
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