Biomedical Engineering Reference
In-Depth Information
remarkable example was reported by Ley and coworkers in the total synthesis of
azadirachtin
240
(Scheme 4.67) [70]. The key crowded C8-C18 bond and
the allene functionality, required for the further construction of the complete
azadirachtin skeleton, were installed by a gold-catalyzed Claisen rearrangement
of the propargylic enol ether
[71]. This transformation is highly illustrative of
the synthetic advantage that can be taken from gold-catalyzed reactions, since the
Claisen compound
238
, which can also be thermally obtained at 185
C under
irradiation (80%), is formed with the same efficiency (80%) but under milder and
more practical conditions.
The less impressive but synthetically useful gold-catalyzed conversion of
alkynes to ketones (hydration) has been used as a new strategy for the synthesis of
prostaglandins and their drug analogues bimatoprost and latanoprost [72]. Zanoni
et al. [72a] and Nolan and coworkers [72b] showed that both propargylic ester
239
241
and
propargylic alcohol
derived from Corey aldehyde can be used as precursors for
the gold-catalyzed formation of the key intermediate enone
242
(Scheme 4.68). This
procedure, which allows introduction of the lower side chain of prostaglandins,
represents an efficient and highly
E
-selective alternative to the more classically
employed but less atom-economical Horner-Wadsworth-Emmons reaction.
Another type of alkyne hydration was reported by Takemoto and coworkers in
their study toward the synthesis of the cytotoxic alkaloid ecteinascidin 743
243
248
(Scheme 4.69) [73]. The real synthetic purpose of the described transformation is
1. LiOH, MeOH/H
2
O/THF
0°C, 20 h
2. (Ph
3
P)AuCl (1mol%)
AgNTf
2
(1mol%)
CH
2
Cl
2
, rt, 3.5 h
3. RNH
2
, rt, 22 h
OMe
OMe
OMe
HO
AcO
HO
AuL
+
Troc
Br
Troc
Br
Troc
Br
N
N
N
CO
2
H
CO
2
Me
80%
+
LAu
O
O
OMs
RNH
2
244
245
246
NH
2
RNH
2
=
O
O
BnO
OMe
O
HO
OMe
OMs
OAc
E
BnO
H
D
OMs
E
N
N
AB
S
C
step
s
D
Br
N
O
NH
O
A
B
O
O
Br
C
N
F
O
OH
BnO
O
O
247
O
O
HO
O
NH
BnO
OMe
MeO
G
H
HO
Ecteinascidin 743
248
SCHEME 4.69
Synthetic studies
toward the synthesis of
the cytotoxic alkaloid
ecteinascidin 743.
Search WWH ::
Custom Search