Biomedical Engineering Reference
In-Depth Information
O
N
O
O
N
N
O
G-II
(20 mol%)
O
O
N
N
N
CH
2
Cl
2
(0.7 mM)
reflux
75%
OTBDPS
OTBDPS
30
31
32
OTBDPS
OTBDPS
G-I
(40 mol%)
CH
2
Cl
2
(0.2 mM), reflux
66%
O
N
O
O
N
H
N
H
N
H
H
H
H
O
G-I
(20 mol%)
O
O
O
O
N
CH
2
Cl
2
(0.5 mM)
reflux, 24 h
70%
N
N
N
O
34
35
33
(
+
)-Nakadomarin A
(
E
/
Z
= 1.7:1)
separable
(
E
/
Z
= 5:3)
inseparable
N
H
N
H
G-I
(15 mol%), (+)-CSA
O
O
N
CH
2
Cl
2
, reflux, 3.5 h
N
62%
36
(
−
)-Nakadomarin A
(
Z
/
E
=
63:37)
(no CSA,
Z
/
E
=
40:60)
SCHEME 5.12
Ring-closing metathesis in the total syntheses of (
þ
)- and (
)-kendomycin
by Nishida and coworkers, Kerr and coworkers, Dixon and coworkers.
(
Z
)-isomer, thereby completing the total synthesis of civetone. In stark contrast,
ring-closing alkene metathesis of diene
39
in the presence of ruthenium catalyst
40
afforded civetone as a mixture of geometric isomers (
E
/
Z
4.6:1) (Scheme 5.13).
Cruentaren A is a benzolactone that exhibits potent cytotoxicity against L929
cell line and acts as an inhibitor of mitochondrial F-ATPase in yeast. In Maier's total
synthesis, recognizing the
cis
-olefin embedded within the macrocyclic scaffold of
cruentaren A, a ring-closing alkyne metathesis/Lindlar hydrogenation sequence was
conceived for the installation of this functionality. Indeed, treatment of diyne
¼
41
with
(
t
-BuO)
3
W CCMe
3
(10 mol%)
PhMe, 80°C, 30 min
65%
or
Mo(CO)
6
(5 mol%)
Chlorobenzene, 7 h
H
2
(1 atm)
Lindlar-Pd
Quinoline, CH
2
Cl
2
94%
O
O
O
37
38
Civetone
F
3
CC
6
H
4
OH, 140°C
59%
PCy
3
Cl
Cl
Ru
Ph
PCy
3
Ph
40
CH
2
Cl
2
, reflux, 24 h
(5 mol%)
O
O
39
72%
Civetone
(
E
/
Z
= 4.6:1)
SCHEME 5.13
Ring-closing alkyne metathesis in the total synthesis of civetone by Furstner
and Seidel.
Search WWH ::
Custom Search