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OH
OTr
N
3
N
3
1) TrCl, py
2) Ac
2
O
1) MeOH, H+
2) (TfO)
2
O, NEt
3
O
O
H
HO
Ac
AcO
O
O
OH
OAc
18
19
18
F
OTf
N
3
S
R
Cu(OAc)
2,
Na ascorbate
H
2
O, 60 °C, 12', 44 %
22
K[
18
F
]F
-
, K
222
N
3
O
O
H
HO
Ac
AcO
O
O
CH
3
CN, 120 °C, 10'
then NaOH
OH
OAc
20
21
30 - 40 %
18
F
O
H
HO
O
N
O
N
N
N
R =
HOOC
COOH
OH
H
S
R
23
NH
2
O
SCHEME 7.4
Elaboration of [2-azidoethyl]-6-fluoro glucosides and coupling with S-
propargylcysteine.
renal excretion. Thus, many radiotracers have been conjugated to sugars by different
ways including the CuAAC.
7.3.2.1 Radiotracers withCovalent Labeling
The short Arg-Gly-Asp (RGD) pep-
tide is a famous sequence found in proteins of the extracellular matrix such as
laminin, fibrinogen, vitronectin involved in the adhesion between cells and extracel-
lular matrix. This sequence is recognized by integrins, heterodimeric transmembrane
proteins, which play a major role in signaling in and out of cells. The vitronectin
receptor or
v
3
integrin is a key receptor expressed on endothelial cells which mod-
ulates migration and survival during angiogenesis. This receptor is also expressed in
tumor cells and plays a role in metastasis. Imaging angiogenesis or tumor cells with
a suitable labeled ligand of
v
3
integrin has become a challenging area in cancer
and cardiovascular diseases diagnosis. Several efficient ligands of
v
3
integrin have
been disclosed and used to prepare imaging tools [29, 39, 48, 50-52].
In a study aimed at defining the influence of the carbohydrate moiety of active
peptide glycoconjugates, Rutjes et al. reported the use of the triazolo glycoamino
acid
26
(Scheme 7.5) [53]. The latter was obtained by CuAAC between the known
2,3,4,6-tetra-
O
-acetyl-glucosyl azide
24
[54] and N-Fmoc-propargyl glycine
25
under
standard conditions, that is, Cu(OAc)
2
, sodium ascorbate,
t
BuOH, H
2
O [55]. The
free glycoamino acid
26
was involved in a solid phase synthesis of the cyclic peptide
c(RGDy-NTGA)
27
. In order to evaluate the validity of the triazole ring as a surrogate
of the amide bond, the analog
29
with an amide linkage was prepared from 2,3,4,6-
tetra-
O
-acetyl-glucosyl amine and aspartic acid. An improved chemical stability
of the triazole ring with respect to the amide bond was found. The triazole ring
was also found compatible with either basic or acidic conditions. Both compounds
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