Chemistry Reference
In-Depth Information
HO
HO
OH
OAc
N
3
N
3
1) (TfO)
2
O, py
2) nBu
4
N
+
AcO
-
CH
3
CN, rt
1) Bu
3
SnO, MeOH
2) Ac
2
O, DMF
O
O
O
O
HO
AcO
OH
OH
65 %
9
1
46%
AcO
AcO
AcO
OH
nBu
4
N
+
NO
2
-
AcO
AcO
AcO
N
3
N
3
O
O
O
O
CH
3
CN, 50°C
OTf
47%
11
12
1) Tf
2
O, Pyr
DAST, diglyme
50 °C, 20'
68%
2)
18
F
-
, Kryptofix
222
CH
3
CN, 85 °C, 5'
3) NaOH
HO
HO
HO
AcO
AcO
AcO
N
3
N
3
O
O
O
O
18
F
F
1
1
SCHEME 7.2
Elaboration of [2-azidoethyl]-2-fluoro glucosides.
out using [
18
F]F
−
and K
222
followed by removal of acetyl groups, led to
13
in 38%
radiochemical yield. Not unexpectedly, it is very important to start from
-anomers
to achieve fluorination at C-2 of 2-
O
-triflyl-
manno
derivatives in significant yields.
Following their preliminary study, Prante et al. developed the [
18
F]-labeling of
alkyne-bearing peptides with concomitant glycosylation (Scheme 7.3) [47]. The
alkyne function was introduced by coupling commercially available L-propargyl-
glycine with the peptide of interest. The method was applied to neurotensin (NT), a
peptidic ligand of neurotensin receptor 1 (NTR-1), a receptor overexpressed in pan-
creatic tumor cells. Radioactive ligands of this receptor should be useful in colorectal
cancer imaging. Different peptidic sequences designed from the NT(8-13) hexapep-
tide were used as a starting point. As an example, several peptides bearing a triple
bond were reacted with [
18
F]fluoroglucosyl azide
15
prepared like [
18
F]FDG starting
from the azidomannosyl triflate
4
via compound
5
. Four labeled glycopeptides like
16
were prepared in 70-80% radiochemical yield by heating the two compounds in PBS
(10% ethanol) at 60
◦
C for 20 minutes in the presence of Cu(SO
4
) and sodium ascor-
bate. Interestingly, the glucose-conjugated c(RGDf)
17
, prepared in 20% yield within
70 minutes, had an excellent
in vivo
metabolic stability, fast tumor accumulation and
compared well with the clinically used [
18
F]galacto-RGD [48].
It is clear that most of the ligation methods to connect a peptide to a prosthetic
group need some modifications of the peptide which could be a limiting step. Our
group recently explored a new approach for the direct derivatization of peptides with
an alkyne residue taking advantage of the unique reactivity of thiol [49]. The thiol
nucleophilicity of cysteine-containing peptide has not been widely used till now.
We were able to selectively introduce a propargyl group on the cysteine residue
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