Biomedical Engineering Reference
In-Depth Information
TiCp
2
AlMe
2
Cl
Tebbe reagent
90°C
TiCp
2
TiCp
2
DMAP, benzene
25°C
t
-BuO
2
C
t
-BuO
2
C
t
-BuO
2
C
127
129
130
Cp
Ti
Cp
128
HOCH
2
CH
2
OH
p
-TsOH
81%
H
H
H
O
H
H
H
H
H
H
O
O
t
-Bu
132
131
(9,12)
-Capnellene
(
±
)-
Δ
SCHEME 5.32
Tandem ring-opening/ring-closing metathesis in the total synthesis of
(9,12)
-capnellene by Grubbs and Stille.
(
)-
D
of tricyclic diterpenoid natural products isolated from the Jamaican sponge
Myrmekioderma styx
and found to display a diverse range of biological activities,
including cytotoxic, antimicrobial, antineoplastic, stimulation of nerve growth factor
synthesis, and
k
-opioid receptor agonism. In their total synthesis of (
þ
)-cyanthiwigin
U, the tandem olefin metathesis precursor alkenyl bis-enone
134
was prepared from
dialdehyde
through a double vinyl Grignard addition/oxidation sequence.
Treatment of substrate
133
with Grubbs second generation catalyst smoothly
delivered the challenging cyclohepta[
e
]indene system
134
)-cyanthiwigin U
in 43% yield. Several ruthenium carbenoid intermediates could be invoked for this
multistep process, resulting from several possible ring-opening and ring-closing
olefin metathesis events, as shown by structures
135
of (
þ
136
-
138
(Scheme 5.33) [62].
)-8-
epi
-Xanthatin is a sesquiterpenoid lactone isolated from various species
of the genus
Xanthium
and has been found to exhibit antimalarial and antitumor
activities, and it is also an inhibitor of the farnesylation of human lamin-B. Martin and
coworkers devised an expedient synthesis of this natural product, demonstrating a
tandem enyne ring-closing metathesis/cross-metathesis as the final step in their
synthesis. The phosphine-free ruthenium catalyst was selected for this transformation
since it is well documented to be more effective in cross-metathesis reactions
involving electron-deficient olefins. Thus, treatment of enyne
(
þ
139
with Grubbs
O
H
H
O
O
H
H
1.
BrMg
2. DMP
, CeCl
3
G-II
(20 mol%)
Ethylene
PhMe, 120°C, 12 h
43% (3 steps)
O
HO
O
Me
Me
Me
O
O
Me
Me
133
134
135
(
+
)-Cyanthiwigin U
O
O
O
H
H
H
H
RuLn
O
Me
O
Me
RuLn
Me
Me
O
LnRu
136 137 138
SCHEME 5.33
Tandem ring-opening/bis-ring-closing metathesis in the total synthesis of
(
þ
)-cyanthiwigin U by Phillips and Henderson.
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