Biomedical Engineering Reference
In-Depth Information
O
SC
6
H
13
O
O
SC
6
H
13
MeSO
3
H (0.01%)
CH
2
Cl
2
Me
Me
NHAlloc
NAlloc
N
N
MeO
MeO
OH
O
OH
O
OBn
OBn
5
6
Me
OH
Me
OH
OMe
OMe
O
O
SC
6
H
13
Me
Me
NAlloc
NAlloc
N
N
MeO
MeO
OH
OB
O
OH
O
OBn
7
8
Me
OH
Me
OH
OMe
OMe
OMe
OMe
HO
Me
R'
R
O
O
OH
Me
N
Me
Me
N
Alloc
O
N
MeO
N
MeO
O
O
O
OH
OB
O
Me
O
9
(R = OH and R
′
= Me)
10
(R = Me and R
′
= OH)
(
9
/
10
= 3.4
:
1)
Me
(-)-Cribrostatin 4
11
SCHEME 9.2
Total synthesis of (
)-cribrostatin 4
(11)
by Zhu and Chen.
Domino oxa- and carbacyclizations are well known in the biosynthesis of
steroids and other more complex natural products [8]. Hardcastle and coworkers have
recently used this method for biomimetic syntheses of durgamone, nakorone, and
abudinol B
[9], three compounds that have recently been isolated from Red Sea
sponges
Ptilocaulis spiculifer
of the Axinellidae family [10]. Hence, treatment of the
enyne diepoxide
(17)
with excellent stereo-
selectivity, which after ozonolysis of the allene moiety and cleavage of the TMS ether
moiety led to
ent
-nakorone
18
with TMSOTf afforded the oxepane
19
(21)
. This compound was further manipulated to afford
ent
-abudinol B (
ent
-
) (Scheme 9.4).
The red tide organism
Gymnodinium breve
-derived natural product
hemibrevetoxin B
17
(26)
was originally reported to elicit characteristic rounding of
cultured mouse neuroblastoma cells and showed cytotoxicity at a concentration of
5
mol [11]. Like its more complicated cousins, the brevetoxins, the binding to
receptors on voltage-dependent sodium channels is assumed to be the source of this
cytotoxicity. In the synthesis of hemibrevetoxin B [12], an advanced intermediate
m
22
was prepared by Holton and coworkers as a biomimetic precursor to the natural
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