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In-Depth Information
44
was reacted with different amino-acid-derived alkynes and the resulting triazoles
46
were then complexed with
99m
Tc to produce the expected radioactive probes
47
(obtained from propargyl glycine as the alkyne component). These compounds were
further transformed into the 5
-monophosphate and tested as substrates of human
cytosolic thymidine kinase (hTK1), a key enzyme in tumor proliferation.
7.3.3 Carbohydrate Labeling
The search for surrogates of [
18
F]FDG and the labeling of biologically significant
and/or complex carbohydrates such as nucleoside or oligonucleotide is very active
and the efficiency of CuAAC has stimulated some researches along these lines which
are reported in this section.
7.3.3.1 Analogs of 2-Deoxy-2-[18F]fluoro-Glucose
[
18
F]FDG is widely used in
all PET centers and its automated synthesis is now well established. Nevertheless, the
search for new labeled sugars as surrogate of [
18
F]FDG is still a challenge. As shown
in Scheme 7.10, the sugar does not carry the label but is coupled to a fluorinated
prosthetic group, taking advantage of CuAAC. Choe et al. constructed the triazolo
glucose derivative
50
[61]. Two methods of
18
F introduction have been investigated.
The first one is based on the elaboration of the triazole
48
obtained by CuAAC of
protected
-azido glucose
24
with homopropargyl alcohol. Subsequent tosylation
followed by nucleophilic displacement with nBu
4
N[
18
F]F in acetonitrile/tBuOH at
100
◦
C for 20 minutes gave the labeled derivative
50
after deacetylation. The second
OAc
OAc
N
N
OH
CuSO
4,
Na ascorbate
t
BuOH/H
2
O, RT 2h
TsCl, NEt
3
O
O
AcO
AcO
Ac
AcO
OH
N
3
N
OAc
OAc
2
4
1) nBu
4
N[
18
F
]F
-
t
BuOH, 100 °C, 20
'
OAc
OH
18
F
OTs
N
N
N
N
O
O
H
HO
Ac
AcO
N
N
2) MeONa, MeOH
OH
OAc
49
50
K[
18
F
]F
OTs
18
F
Kryptofix
222
CH
3
CN, 100 °C, 20'
51
52
CuI, Na ascorbate
tBuOH/H
2
O, rt 2h
OH
O
HO
HO
N
3
OH
SCHEME 7.10
Synthesis of
18
F labeled triazolyl-glucose.
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