Biomedical Engineering Reference
In-Depth Information
TBSO
OTBS
1. MeLi, HMPA, THF
-78°C to 0°C
O
H
S
S
+
Li
MeO
CO
2
Me
2. NaOMe, MeOH
0°C to reflux
O
OTMS
46
47
48
R
O
OMe
MeO
2
CH
2
OTBS
OTBS
H
1,6-stereo-
control
O
H
O
Li
H
OMe
S
86%
O
H
S
O
H
H
50
49
Solanapyrone D
51
(R = CHO)
Solanapyrone E
52
(R = CH
2
OH)
SCHEME 9.10
Synthesis of solanapyrones D and E.
product within 24 h, whereas initial trials using model compounds needed over
10 days.
The solanapyrones D
(51)
and E
(52)
isolated from
Alternaria solani
are part of
a larger solanapyrone family of
trans
-or
cis
-decalin natural products. This family of
compounds has attracted attention in the chemical community because of its origin,
which includes several fungi that cause early blight disease in tomato, potato and
chickpea plants. Various other biological effects such as antialgal activity are still
being explored. Hagiwara and coworkers approached the synthesis of the solanapyr-
ones D and E through a domino Michael/Michael addition to give bicyclo[2.2.2]
octanes with the enantiopure bis-silyl ether
46
and crotonate
47
as substrates
(Scheme 9.10) [21]. In the reaction, the bis-silyl ether
46
was proposed to form the
dichelated intermediate
48
that then underwent the first Michael addition to afford
49
.
In this addition, the attack at the less hindered
-face of the enolate is probably
a
controlled by the stereogenic center in
. The second Michael addition also occurred
from the same face to provide compound
46
as a mixture of its
cis
- and
trans
-
diastereomers. The
cis-isomer
, however, could be isomerized upon treatment with
sodium methoxide in methanol to give mainly
trans
-isomer, which was eventually
converted to the desired natural product.
The marine natural product (
50
containing a
cis
-fused
pyrroloindoline core from
Flustra foliacea
is shown to block voltage-activated
potassium channels [22] and has both skeletal and smooth muscle relaxant activities.
MacMillan and coworkers devised a domino Michael/cyclization reaction for their
synthesis with an enantioselective introduction of two stereogenic centers [23]. Thus,
treating the protected tryptamine derivative
)-flustramine B
(58)
53
with an iminium ion presumably
formed as an intermediate by reaction of acrolein
in the presence of a catalytic
amount of the enantiopure imidazolidinone, provided intermediate
54
. An ensuing
intramolecular reaction with the
N
-Boc tether and the subsequent hydrolysis gave
aldehyde
55
56
, which was immediately reduced to yield
57
. The overall process
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