Biomedical Engineering Reference
In-Depth Information
TMS
H
TMS
CH
3
H
t-
BuLi, TMEDA, THF
-40°C, 1 h, CuI, TMSCl
THF, -78°C, 2 h
H
O
H
O
32
33
BF
3
·OEt
2
, HC(OMe)
3
CH
2
Cl
2
, -20°C, 1 h
O
H
HN
TMS
H
HO
steps
OMe
H
O
OMe
NH
H
O
34
Cylindramide
35
O
OH
SCHEME 9.7
Total synthesis of cylindramide
(35)
by Laschat and coworkers.
39
, a ionophore of an acyltetronic acid containing 12 stereogenic centers, among
them many contiguous, presents a demanding synthetic challenge. The natural
product demonstrates a range of biological activities, including antibiotic [18]
and antiparasitic activities, and it acts as a growth-promoting agent in ruminants.
The preparation of this compound, produced from
Streptomyces longisporo-
flavus
, was accomplished through a convergent synthesis devised by Ley and
coworkers (Scheme 9.8) [19]. In the later stages of this synthesis, the tetraene
36
was treated with potassium hexamethyldisilazide to first initiate a conjugate
addition of the secondary alcohol to the dienic ester. Following a subsequent
reequilibration of the addition product (enolate), a second cyclization occurred in
EtO
2
C
KHMDS
MeO
2
C
EtO
2
C
HO
O
O
O
H
H
H
H
H
H
OMe
Toluene, 0°C
OMe
CO
2
Me
36
37
Acetic acid
workup
67%
HO
O
O
EtO
2
C
H
H
H
H
O
OMe
O
H
H
H
H
steps
OMe
O
H
O
4
Tetronasin
39
38
Na
H
CO
2
Me
O
O
SCHEME 9.8
Synthesis of tetronasin
39
by Ley and coworkers.
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