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In-Depth Information
OTf
AcO
AcO
AcO
HO
HO
HO
AcO
Ac
AcO
K[
18
F
]F, K
222
NaOH
O
O
O
N
3
N
3
N
3
K
2
CO
3,
KH
2
PO
4,
5 min, 60 °C
18
F
18
F
CH
3
CN, 2.5 min, 85 °C
15
4
5
HO
H
HO
O
N
N
O
N
H
2
N
HN
R
18
F
O
1. HCl (0.1M);
2. PBS (10% ethanol),
CuSO
4
, sodium ascorbate,
20 min, 60 °C
H
2
N
HN
Arg-Pro-Tyr-Ileu-Leu
16
NH
HO
HO
HO
N
N
O
HN
NH
2
N
18
F
O
O
NH
HN
O
NH
HN
N
O
17
O
COOH
SCHEME 7.3
Labeling pentapeptides with 1-azido-2-fluoro glucose using CuAAC.
of several native peptides by simple treatment with propargyl bromide in aqueous
basic solution (Ba(OH)
2
or NH
4
OH) for 2 hours at 0
◦
C. This methodology has
been successfully applied to glutathione as a model peptide and to the tetrapeptide
RGDC (Arg-Gly-Asp-Cys) (Scheme 7.4). The CuAAC coupling with different azido
sugars in water at room temperature in the presence of copper acetate and sodium
ascorbate proceeded uneventfully. In the meantime, we have developed new fluoro
sugar prosthetic groups. We took advantage of the high reactivity of the primary
position to introduce a fluorine atom at C-6 using 6-
O
-triflyl derivatives like
20
.The
latter were prepared from the azido sugars
18
by a classical sequence of protection-
deprotection using the trityl derivatives
19
. The labeling sequence with [
18
F]F
−
has
been applied in the
gluco
and
manno
series with radiochemical yields of 63% and
64% respectively. The CuAAC sequence was carried out with the
gluco
derivative
21
and the propargylated glutathione
22
using classical conditions (Cu(OAc)
2
, sodium
ascorbate, water, 60
◦
C, 12 minutes) to provide the labeled glutathione derivative
23
.
This shows that 6-deoxy-6-fluoro sugars are good candidates as prosthetic groups.
7.3.2 Glycoconjugation of Radiotracers
As mentioned above, sugar conjugation to a radiotracer strongly modifies the phar-
macological properties by reducing lipophilicity, plasma protein binding, hepatic
uptake, hepatobiliary transfer or unspecific uptake, and increasing tumor uptake and
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