Biomedical Engineering Reference
In-Depth Information
CHO
O
O
1.
, EtOAc, rt, 45 min
OH
OH
OH
NMe
3
BH
4
, MeOH/CH
2
Cl
2
, 2 h
1. TMSCl, MeOH, rt, 12 h
2.
2.
3. NH
2
Me, 40°C, 24 h
3. (CF
3
CO)O
2
, CH
2
Cl
2
, 0°C, 1 h
NEt
2
H
O
N
CONHMe
NHMe
H
2
N
CO
2
H
H
2
N
N ,
DMAP
COCF
3
O
O
91% (over 6 steps)
35
36
37
I(OAc)
2
5
82%
CF
3
CH
2
OH, -5°C
MeO
O
1.
NMe
3
OH
1.
CF
2
SO
3
H (Nafion-H), 24 h
Me
H
MeOH,
W, 100°C
20 min (96%)
μ
N
O
O
2.
NMe
3
BH
3
, MeOH/CH
2
Cl
2
, 2 h (100%)
CONHMe
O
O
N
H
N
CF
3
3.
SO
3
H, TMSCHN
2
, MeOH/CH
2
Cl
2
(95%)
O
CF
3
2.
NEt
3
NaCO
3
39
O
O
38
Br
HO
1.
MeCN,
μ
W, 140°C, 2 x 15 min
MeO
N
MeO
N
3.
SH
H
Me
H
CrO
3
, CH
2
Cl
2
, -45°C
H
Me
N
N
O
O
2.
SO
3
H
O
O
O
H
O
H
N
N
3. Mixed clay frit
86% (2 steps)
O
40
70% (3 steps)
(+)-Plicamine
41
HO
OH
SCHEME 11.5
The first synthesis of (
þ
)-plicamine
41
using a combination of immobilized
reagents and scavengers.
(Scheme 11.5) [11]. Impressively, the entire synthesis including optimization was
complete within 6 weeks. A key feature of this synthesis was the use of
immobilized hypervalent iodine
5
for the oxidative transformation to the spir-
odienone
. Also, the conjugate addition of the amidic nitrogen atom to complete
the natural product scaffold (
38
) using Nafion-H fluorosulfonic acid resin as
an acid source was an attractive feature. Similarly, the use of an immobilized
sulfonic acid resin in combination with trimethylsilyl diazomethane proved to be a
particularly efficient way to methylate the hindered alcohol and afford
38
to
39
.
Enzymes are valuable tools for asymmetric synthesis, most notably in the
desymmetrization of
meso
-compounds, where achiral starting materials can be con-
verted into enantiomerically enriched materials. Since enzyme preparations are
expensive, being able to recycle them using immobilization techniques is important.
To do so, enzymes can be covalently attached to insoluble supports and adsorbed onto
various materials, thereby facilitating recovery through filtration. In 2002, the first
reported combined application of immobilized enzymes together with supported
reagents in the preparation of GABA analogues appeared (Scheme 11.6) [15].
Here, the synthesis used commercially available Eupergit-immobilized pig
liver esterase to terminally differentiate
meso
-diester
39
42
in an asymmetric fashion.
45
46
Also of note in this work is the conversion of bromide
into azide
by application
of immobilized reagents. The resulting hazardous azide product
46
was not isolated
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