Chemistry Reference
In-Depth Information
CO
2
H
HO
2
C
CO
2
H
CO
2
H
CO
2
H
HO
2
C
HO
2
C
HO
2
C
NH
3
5-AIPA
NH
2
NH
NH
N
H
+
O
O
O
1
O
Cl
Cl
H
2
N
NH
Cl
R
R = Boc or CBz
CO
2
Bu
BuO
2
C
CO
2
Bu
CO
2
Bu
BuO
2
C
BuO
2
C
NH
3
[H]
NH
2
NH
NH
2
O
CO
2
Bu
O
O
BuO
2
C
Br
Br
Br
H
2
N
NO
2
FIGURE 14.11
Synthesis of aryl-glycine (AG) building blocks [87].
The developed synthesis of AG dendrons relies on the classic Fischer's haloacyl
halide method [88] for the synthesis of building blocks
in Figure 14.11.
This scheme is inexpensive and easily scalable to multigram quantities. Neither of
the intermediate products needs to be isolated and purified. They can be introduced
into the following transformations directly from the preceding syntheses, following
the precipitation upon acidification or evaporation of the solvent. Building blocks
1
and
2
1
and
are obtained in high yields and isolated by precipitation/crystallization.
Synthesis of AG dendrons in principle also can be implemented using the Fischer's
method [87], however, a more robust scheme is based on a coupling-deprotection
sequence employing the peptide-coupling reactions (Figure 14.12) [89].
2
CO
2
Bu
BuO
2
C
CO
2
Bu
HN
O
O
N
H
CO
2
Bu
N
H
H
N
BuO
2
C
O
O
H
N
O
Boc-NH-AG
2
-OBu
HN
H
N
H
O
Boc
HBTU
DIPEA
BuO
2
C
O
HN
O
H
N
O
N
H
O
NH
O
CO
2
Bu
1
+
2
O
NH
2
H
2
N-AG
3
-OBu
H
(2 mol)
TFA
CO
2
Bu
O
H
O
HN
BuO
2
C
O
N
O
HBTU
DIPEA
H
2
N-AG
2
-OBu
N
H
TFA
O
BuO
2
C
NH
O
Boc-NH-AG
3
-OBu
1
(1/2 mol)
HN
BuO
2
C
CO
2
Bu
FIGURE 14.12
Synthesis of poly(aryl-glycine) (AG) dendrons. TFA, trifluoroacetic acid;
HBTU, o-benzotriazole-N,N,N
0
,N
0
-tetramethyl-uronium hexafluorophosphate; DIPEA, N,
N-diisopropylethylamine [89].
