Biomedical Engineering Reference
In-Depth Information
O
O
O
OMOM
OH
OMOM
OH
N
SePh
BnO
OTIPS
BnO
OTIPS
Me
Me
Me
BnO
Me
BnO
O
O
O
O
O
R
(CF
3
)
2
CHOH, 0°C
R
O
O
H
H
H
H
SePh
O
22
(R = )
O
23
O
H
O
OMOM
OMOM
BnO
OTIPS
BnO
OTIPS
Me
O
Me
H
O
Me
Me
BnO
O
O
O
BnO
83%
R
R
O
O
O
H
H
H
H
H
H
H
SePh
SePh
25
24
OH
Me
H
H
O
H
O
O
O
O
H
H
H
HO
Me
H
H
Hemibrevetoxin B
26
SCHEME 9.5
Total synthesis of hemibrevetoxin B
(26)
.
diastereomer. This later compound was taken through to the tetracyclic natural
product in a biomimetic total synthesis that was completed in 39 steps with
approximately 4% overall yield.
The stemona alkaloids bearing a pyrrolo [1,2-
a
]azepine central core often
display a diverse range of biological profiles. The stemona family is widespread
in the monocotyledonous plants comprising of the genera
Stemona
,
Croomia
,and
Stichoneuron
. The secondary metabolite (
, isolated from
Stemona
japonica
, has been reported to have antitussive and anthelmintic properties. In
pursuit of an efficient formation of the pyrrolidine and butyrolactone ring, Williams
and coworkers devised a twofold cyclization process. The enantiopure azepine
precursor
)-stemonine
(31)
27
was first prepared from an enantiopure lactone known within the
Williams group [14]. In the later stages of this synthesis, treating compound
27
with
iodine initiated the first cyclization, presumably through the iodonium ion, to form
the intermediate alkyl iodide
(Scheme 9.6) [15]. Following the formation of
the aziridinium salt and an iodide-mediated second ring closure to the butyrolactone
moiety, the tricyclic ring system
29
was isolated. The excellent stereoselectivity
observed in this process is initially controlled through the kinetically favored
formation of
28
, which subsequently forms an aziridinium salt. The enantiopure
product of this bis-cyclization process was then taken through to the natural product
that was finally obtained in 23 steps.
28
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