Biomedical Engineering Reference
In-Depth Information
CO
2
Et
OMe
TBSO
CO
2
Et
H
CO
2
Et
H
Ar
Ar
TBSO
+
OTBS
OMe
CHO
H
H
PO(EtO)
2
243
244
245
246
OSO
3
H
N
H
OH
H
H
Neosymbioimine
242
SCHEME 9.41
Synthesis of neosymbioimine
242
by Maier and coworkers.
A highly efficient domino process starting with the formation of an iminium ion
followed by a Mannich and a Michael reaction was developed by Shibasaki and
coworkers for the enantioselective synthesis of (
þ
251
) [95]. The
cylindricines, isolated from the marine ascidian
Clavelina cylindrica
by Blackman
et al. [96], are potent anticancer agents against leukemia and also solid tumor
cells [97]. As starting material for their synthesis, Shibasaki and coworkers used
acyclic imine
)-cylindricine C (
247
, which was obtained by a catalytic asymmetric Michael reaction.
Treatment of
with CSA in the presence of LiCl led to a 89:6:5 mixture of
diastereomers with
247
250
as the main product in 57% yield, probably via
248
and
transition state
. Additives such as LiCl had a strong influence on the yield and the
diastereoselectivity, though their mode of action remains so far unclear. Straightfor-
ward transformations of
249
250
then led to (
þ
)-cylindricine C (
251
) (Scheme 9.42).
)-chinensiolide B displaying a broad range of
bioactivities [98], Hall and Elford [99] used a domino allylboration/lactonization.
For the total synthesis of (
þ
OH
O
C
6
H
13
CSA (3 equiv)
LiCl (3 equiv)
3
OH
5
O
N
Ph
ClCH
2
CH
2
Cl, 50°C
42%
H
C
6
H
13
N
CO
2
Bn
H
CO
2
Bn
BnO
2
C
N
Ph
H
13
C
6
247
248
249
O
O
N
N
C
6
H
13
HO
BnO
2
C
C
6
H
13
(+)-Cylindricine C
251
250
SCHEME 9.42
Synthesis of cylindricine C (
251
) by Shibasaki and coworkers.
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