Biomedical Engineering Reference
In-Depth Information
N
PMBO
PMBO
PMBO
O
HG-II
(10 mol%)
30 min addition; then 2 min
1,2-dichloroethane, 50°C
TBSO
O
TBSO
O
TBSO
O
N
OMe
OH
O
O
O
O
O
O
O
O
O
71%
RuLn
103
105
106
(
−
)-Oximidine III
PMBO
TBSO
O
O
O
104
SCHEME 5.28
Relay ring-closing metathesis in the total synthesis of (
)-oximidine III by
Porco and coworkers.
LnRu
71% yield, presumably through the intermediacy of ruthenium carbene
with the
extrusion of cyclopentene. It is worth noting that the corresponding
E
-epoxy-alkene
failed to give the desired metathesis product
105
, and only a complex mixture of
oligomeric by-products was formed. These results suggested that the
Z
configuration
of the epoxy-alkene was essential for a fast reaction rate in the first ring-closing
metathesis step (Scheme 5.28) [53].
In the total synthesis of (
106
)-archazolid B, a potent and selective inhibitor
against mammalian V-ATPases, Trauner and coworkers implemented a related
relay ring-closing alkene metathesis with a carefully designed substrate
107
.Inthe
107
presence of Grubbs second generation catalyst,
underwent ring-closing
metathesis to afford the macrocyclic core of archazolid B in 27% yield. The
successful execution of this daring ring-closing event by means of alkene
metathesis in the presence of multiple sites of olefinic moieties was noteworthy
(Scheme 5.29) [54].
Lee and Cho further expanded the concept of relay metathesis and developed an
ingenious tandem strategy by combining with a metallotropic [1,3]-shift and cross-
metathesis
in their
total
synthesis of
the broad-spectrum antitumor agent
(
, treatment
withGrubbs second generation catalyst initiated the cascade processwith the extrusion
of dihydrofuran
)-(3
R
,9
R
,10
R
)-panaxytriol [55]. Starting with diene-diyne substrate
108
109
and the generation of the ruthenium carbene species
110
.
Transient species
110
then underwent metallotropic [1,3]-shift and cross-metathesis
Me
Me
MeO
MeO
Me
Me
OTBS
OH
OH
OH
1.
G-II
(5 mol%)
PhMe, 110°C, 2 h, 27
%
2. HCOOH/THF/ H
2
O
(3:6:1), 84%
O
O
Me
Me
O
O
N
N
S
S
O
O
MeHN
MeHN
O
O
107
(
−
)-Archazolid B
SCHEME 5.29
Relay ring-closing metathesis in the total synthesis of (
)-archazolid B by
Trauner and coworkers.
Search WWH ::
Custom Search