Biomedical Engineering Reference
In-Depth Information
MeO
O
MeO
O
O
O
PdCl
2
(PPh
3
)
2
(5 mol%)
MeOH, 4 MPa CO, 60°C
I
OTBS
OTBS
OTBS
+
69%
OTBDPS
OTBDPS
OTBDPS
345
(10
R
,11
S
)-
346
(10
S
,11
S
)-
346
2.6:1
MeOLi/MeOH
H
R
2
R
1
O
O
O
O
(-)-Neovibsanin A (R
1
=
OMe, R
2
= Me,
347
)
(+)-Neovibsanin B (R
1
Me, R
2
= OMe,
348
)
=
SCHEME 9.60
Formal synthesis of neovibsanin B
348
by Esumi and coworkers.
) belong to the group of diterpenoids and show
neurotropic activity that makes them interesting targets for the development of drugs
against Alzheimer's disease. Esumi and coworkers have now published the first
enantioselective approach to (
þ
)-neovibsanin B (
348)
using the Negishi palladium
(0)-catalyzed cyclic carbopalladation-carbonylative domino reaction in the presence
of MeOH [130]. After several trials, treatment of
Neovibsanins A (
347
) and B (
348
345
with 4MPa of CO in 24 equiv of
MeOH at 60
C gave the two diastereomers (10
R
)-
in a 2.6:1 ratio
and 69% yield. Fortunately, the undesired diastereomer could be isomerized to
(10
R
)-
346
and (10
S
)-
346
. Further transformations using Nishizawa's approach for the last step
finally afforded (
346
þ
)-neovibsanin B (
348
) (Scheme 9.60).
are very important antibiotics; they have been isolated
from the fermentation broth of
Streptomyces
and other microorganisms [131]. Tietze
and coworkers developed a domino Tsuji-Trost/Heck reaction for the formation of
the complete ABCD ring system of these compounds [132]. Thus, reaction of
Tetracyclines such as
351
349
with NaH in DMF with a catalytic amount of Pd(OAc)
2
and dppe as ligand led to
350
in 65% yield (Scheme 9.61).
Biyouyanagin A (
360
) shows a remarkable activity against HIV replication in
H9 lymphocytes (EC
50
¼
g/mL) [133], as well as some other biological
activities. It was isolated from
Hypericum
species
H. chinese
L. var.
salicifolium
[134].
Nicolaou and coworkers developed an efficient multicomponent Pd-catalyzed dom-
ino process to prepare the spiro moiety of
0.798
m
360
(Scheme 9.62) [135]. Thus, reaction of
352
and iodobenzene with Pd(PPh
3
)
4
in the presence of CO, CO
2
, and Et
3
N led to the
desired
359
in 79% yield via the probable intermediates
353
-
358
. Product
359
was
further transformed into the natural product
.
One of the most important reactions based on Pd(II)-catalysis is the Wacker
oxidation that among other applications is used industrially in the synthesis of acet-
aldehyde starting from ethene. A domino reaction combining this process with a Heck
reaction has been successfully applied by Tietze and coworkers for an efficient
enantioselective
360
synthesis of
-tocopherol
365
using a BOXAX ligand
a
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