Biomedical Engineering Reference
In-Depth Information
C
8
F
17
C
8
F
17
O
1. C
8
F
17
(CH
2
)
3
OH
R
1
CHO, CHCl
3
μ
O
O
O
H
O
DCC, DMAP
W, 15 min
OH
NHBoc
NH
NH
3
.TFA
2. TFA
F-SPE
80-92%
HN
F-SPE
R
1
H
H
47
48
49
O
H
O
R
2
NCO
H
O
C
8
F
17
H
N
R
2
N
O
N
F-SPE
Et
3
N
CH
2
Cl
2
25
o
C, 3 h
H
R
2
N
N
H
R
1
O
R
1
50
51
SCHEME 10.10
Fluorous amino ester for the synthesis of tetrahydro-
b
-carboline hydantoins.
then subjected to a Pictet-Spengler reaction with various aldehydes to form tetra-
hydro-
-carboline derivatives
49
. Treatment of the latter with isocyanates finally led
to the formation of ureas
50
that spontaneously underwent cyclization to afford
hydantoin-fused tetrahydro-
b
-carbolines
51
as the major products.
b
10.4.
FLUOROUS DIVERSITY ORIENTED SYNTHESIS (DOS)
A common reaction intermediate can be employed for DOS of different library
scaffolds with substitution and skeleton variations. In this context, Zhang and
coworkers developed a [3
2] cycloaddition/de-tag/cyclization protocol for DOS of
hydantoin-, piperazinedione-, and benzodiazepine-fused heterocyclic scaffolds such
as
54
,
55
, and
56
(Scheme 10.11) [39]. Each of these three scaffolds had four
þ
O
O
CHO
R
1
O(CH
2
)
3
C
8
F
17
52
+
+
R
3
N
NH
2
R
2
O
TEA, DMF
μ
W
130°C, 20 min
O
O
O
R
4
H
1
O
R
O
R
1
O
H
R
3
1
R
H
3
N
NH
R
R
4
N
3
N
R
N
O(CH
2
)
3
C
8
F
17
NH
N
O
N
H
O
H
O
O
H
O
53
54
56
2
R
2
R
R
2
O
H
O
R
4
R
1
N
N
1
R
N
O
O
H
N
O
4
O
R
O
1
O
2
H
R
3
R
R
N
3
R
R
2
N
N
Inhibitors of human hormone-
sensitive lipase
Tricyclic thrombin inhibitors
O
H
O
55
2
R
SCHEME 10.11
Fluorous amino ester-based DOS of three heterocyclic scaffolds.
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