Biomedical Engineering Reference
In-Depth Information
CHO
O
123
9
OH
OBn
BF
3
·Et
2
O
2,6-DTBP
O
OH
O
O
OMe O
steps
+
O
CH
2
Cl
2
, 78°C
78%
TMS
OBn
OTIPS
O
O
124
125
(dr = 5.5:1 at C9)
Leucascandrolide A
126
OTIPS
SCHEME 9.23
Synthesis of leucascandrolide A
126
by Rychnovsky and coworkers.
5.5:1 diastereomeric ratio (78% yield) in favor of the desired epimer is controlled by
the
-stereogenic center within compound
123
. The advanced intermediate
125
is
b
carried through to the production of leucascandrolide A (
) (Scheme 9.23).
A large group of diterpenes containing an otherwise rare oxacyclic core are
produced bymarine invertebrates. SclerophytinA (
126
) belonging to these compounds
was prepared by Overman and coworkers using a two-component domino reac-
tion of diol
132
127
and
a
,
b
-unsaturated aldehyde
128
in the presence of BF
3
OEt
2
(Scheme 9.24) [55]. One can assume that first oxenium ion
129
is formed, which then
undergoes a cyclization to give the carbocation
130
. The final step in this domino
131
process is a ring contraction to provide
with an annulated tetrahydrofuran moiety.
Compound
.
The domino Mukaiyama aldol/lactonization sequence has been used by Romo
and coworkers with great success, targeting the two natural products panclicin D
(
131
is then further elaborated to give the natural product
132
) that show potent pancreatic lipase inhibition [56,57].
In both cases, a thiopyridylsilylketene,
137
) and okinonellin B (
141
134
or
139
, is reacted with an appropriate
TIPSO
CHO
OH
F
3
BO
F
3
BO
128
BF
3
·OEt
2
, MgSO
4
CH
2
Cl
2
, -55°C to -20°C
79%
R
O
O
OH
R
R
TIPSO
TIPSO
127
129
130
TMS
(R = )
Me
H
H
H
H
CHO
H
steps
H
H
O
O
HO
HO
OH
Sclerophytin A
132
OTIPS
131
TMS
SCHEME 9.24
Synthesis of sclerophytin A
132
by Overman and coworkers.
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