Biomedical Engineering Reference
In-Depth Information
Negishi
coupling
Wittig
olefination
H
OH
Intramolecular
Barbier-type
macrocyclization
O
H
O
HO
HO
O
(-)-Kendomycin
140
FIGURE 2.8
Retrosynthetic analysis of (
)-kendomycin
140
.
OTMS
CO
2
Me
I
SiMe
2
Ph
(
E
)-
syn
-
141
[4+2] -Annulation
17 steps
H
OMOM
O
+
H
OMe
9%
TBSO
OHC
OMe
TBSO
BnO
OMe
OMe
142
143
1.
I
OTBS
144
92%
t
-BuLi, ZnCl
2
, Et
2
O
-78 to 0°C
2. Pd(PPh
3
)
4
(10 mol%)
143
, THF, rt
OTBS
H
OMOM
8 steps
18%
O
(-)-Kendomycin
140
H
OMe
TBSO
TBSO
OMe
145
SCHEME 2.38
Synthesis of the aliphatic ANSA system of (
)-kendomycin
140
.
SmI
2
-assisted intramolecular Barbier-type cyclization reaction, affording the
quinone methide chromophore on the pseudo
C
-glycosidic bond (Scheme 2.38).
(
could thus be obtained in 26 steps and 1.51% overall yield,
starting from (
E
)-
syn
-crotylsilane
)-Kendomycin
140
141
.
2.2.3.3. Bryostatin Bryostatin
is a 26-membered macrolactone belonging
to a family of marine natural products with biological activities against several cancer
cell lines
in vivo
. Its ring-expanded analogue
146
147
, which retains the functionalities of
the parent compound
146
, inhibits the growth of breast cancer NCI-ADR cell line
with an IC
50
¼
123 nM (in the same assay, for discodermolide IC
50
¼
240 nM) [79]
Search WWH ::
Custom Search