Biomedical Engineering Reference
In-Depth Information
1. BH
3
.
SMe
2
, -10°C to rt
2.
_
+
Pig Liver Esterase
0.1 M Phosphate buffer
0.5 M NaOH, pH 7, rt
NBn
3
OH
O
MeO
2
C
CO
2
Me
HO
2
C
CO
2
Me
O
SO
3
H
3.
42
44
43
(95% ee)
4.
DMAP
98%
68% (4 steps)
1. SOBr
2
, M
e
OH
2.
85%
N
_
+
NMe
3
I
1. H
2
, Pd/C, Boc
2
O
2.
H
N
N
3
Br
Boc
CO
2
Me
CO
2
Me
NH
2
+
_
CO
2
Me
H
NMe
3
N
3
47
46
45
84%
95% (2 steps)
1.
2. 1 M HCl, reflux
SO
3
H
67%
HCl
.
H
2
N
O
OH
48
SCHEME 11.6
Representative synthesis of GABA analogues.
but directly reduced with palladium on carbon to the amine derivative itself, being
trapped as its Boc-protected derivative
in an excellent 95% yield after scavenging
of the excess reagents. An acid catch-and-release using a sulfonic acid resin finally
afforded the hydrolyzed hydrochloride salt of the cyclopropanyl GABA analogue
47
.
A further illustration of the power of immobilized reagents was during the
synthesis of the natural product carpanone
48
. Beguiling in its apparent complexity,
carpanone was obtained in a simple series of reactions from commercially available
sesamol
55
(Scheme 11.7) [16].
Sesamol
49
was first
O
-alkylated with allyl bromide in the presence of
immobilized phosphazine base BEMP to give
49
50
, which then underwent a Claisen
rearrangement to
51
using focused microwave heating with a combined solvent
Ph
2
P
PF
6
Ir(THF)
2
H
2
PF
6
Br
N
N
Ph
2
52
MeCN, DMF
W
3 x 15 min, 220°C
toluene,
μ
O
O
BEMP
O
O
O
O
O
O
THF
OH
98%
O
97%
OH
100%
OH
50
51
53
Sesamol
49
O
N
N
O
Co
1.
O
O
O
H
54
O
O
2
, CH
2
Cl
2
O
O
H
2.
O
NEt
3
NaCO
3
O
O
NH
2
NH
2
3.
(±)-Carpanone
55
N
H
(Trisamine)
70% (over 3 steps)
SCHEME 11.7
Synthesis of carpanone
55
.
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