Substrate Activity of Technetium and Thymidine Derivatives
Bioconjugate Chem., Vol. 21, No. 4, 2010 631
J ) 6.6, 1H), 4.68 (t, J ) 5.7, 2H), 4.37 (t, J ) 5.6, 3H),
(m, 2H), 2.86-2.74 (m, 1H), 2.27 (m, 1H) ppm. 13C NMR
3
.92-3.85 (m, 3H), 3.80 (dd, J ) 12.0, 3.1, 1H), 3.74-3.70
3
(CD OD) δ 166.42, 152.40, 151.52, 138.40, 125.44, 111.65,
(
3
dd, J ) 12.0, 3.8, 1H), 3.72 (s, 3H), 2.24 (ddd, J ) 13.6, 6.2,
87.03, 86.92, 86.23, 85.88, 63.81, 63.66, 62.60, 62.37, 44.65,
.9, 1H), 2.16 (ddd, J ) 11.4, 6.6, 1H), 1.85 (d, J ) 1.0, 3H)
39.03, 34.23, 12.61 ppm. High res. MS (ESI) m/z 653.0818
1
3
+
ppm. C NMR (CD
1
3
OD) δ 165.08, 152.25, 136.76, 125.04,
[C18
H
22
N
6
O
7
ReS] (calc. 653.0822).
10.37, 88.96, 87.10, 71.92, 62.57, 43.87, 42.08, 41.54, 13.13
1
[
Re(CO)
3
9]NEt
4
. (30 mg, 45%). H NMR (CD
3
OD) δ 8.20
+
ppm. High res. MS (ESI) m/z 439.1933 [C18
39.1936). The intermediate (112 mg, 0.26 mmol) was dissolved
in a mixture of H O (2 mL) and 1 M NaOH (0.5 mL) and stirred
26 6 7
H N O ]H (calc.
(
(
1
s, 1H), 7.89 (d, J ) 1.1, 1H), 6.46 (t, J ) 6.4, 1H), 5.57-5.47
4
m, 1H), 4.43 (dt, J ) 6.1, 3.2, 1H), 3.95 (dd, J ) 12.4, 3.0,
2
H), 3.85 (dd, J ) 12.4, 3.3, 1H), 3.61 (t, J ) 4.7, 1H), 3.44
for 2 h at rt. The mixture was neutralized by addition of 1 M
HCl, before being concentrated under reduced pressure. The
crude product was purified by solid phase extraction using a
Sep-Pak column. The fractions containing the product were
(
(
(
d, J ) 4.7, 2H), 3.37-3.28 (m, 8H), 3.06-2.93 (m, 1H), 2.84
ddd, J ) 14.3, 8.7, 5.8, 1H), 1.93 (d, J ) 1.1, 3H), 1.35-1.27
13
m, 12H) ppm. C NMR (CD
3
OD) δ 198.32, 179.91, 179.88,
66.42, 152.23, 147.36, 138.48, 126.96, 111.65, 86.92, 86.10,
2.05, 62.03, 53.82, 53.31, 53.28, 53.25, 38.79, 27.02, 12.46,
.59 ppm. High res. MS (ESI) m/z 680.00629 [C19H N O11Re]
19 5
evaporated under reduced pressure to give 10 as a white solid
1
(
6
(
3
70 mg, 61%). H NMR (CD
3
OD) δ 7.97 (s, 1H), 7.82 (s, 1H),
+
.16 (t, J ) 6.6, 1H), 4.68 (t, J ) 5.6, 2H), 4.37 (m, 3H), 3.98
s, 2H), 3.90 (q, J ) 3.4, 1H), 3.79 (dd, J ) 12.0, 3.1, 1H),
1
1
[
Re(CO) 10]. (58 mg, 83%). H NMR (CD OD) δ H NMR
3
3
.72 (dd, J ) 12.0, 3.8, 1H), 3.31 (s, 2H), 2.25 (ddd, J ) 13.5,
.1, 3.8, 1H), 2.15 (ddd, J ) 13.5, 6.6, 1H), 1.86 (s, 3H) ppm.
6
1
3
C NMR (CD OD) δ 176.69, 165.06, 152.03, 145.19, 136.79,
3
H), 4.36-4.22 (m, 2H), 3.88 (dd, 1H), 3.83-3.77 (m, 1H),
1
25.45, 110.43, 88.81, 87.25, 71.77, 62.64, 52.00, 43.92, 41.88,
.81 (d, J ) 17.3, 1H), 3.38 (d, J ) 17.3, 1H), 3.04-2.93 (m,
4
1.34, 13.07 ppm. High res. MS (ESI) m/z 425.1776
13
3
OD)
+
[
C
17
H
24
N
6
O
7
]H (calc. 425.1779).
δ 197.37, 196.71, 183.78, 166.35, 152.20, 149.87, 138.37,
124.04, 111.79, 86.68, 85.88, 62.93, 61.86, 56.29, 53.09, 38.38,
12.50 ppm. High res. MS (ESI) m/z 651.0838
Compound 16. As per general procedure A, with 1 (280 mg,
.90 mmol) and 6 (131 mg, 0.88 mmol). The product was
0
+
extracted into EtOAc and washed twice with saturated NaCl.
The aqueous phases were re-extracted with EtOAc. The organic
[C H N O Re]H (calc. 651.0844).
1
8
19
6
9
1
1
[
3 3
Re(CO) 11]Br. (64 mg, 55%). H NMR (CD OD) δ H NMR
phases were combined, dried over Na
reduced pressure. The crude product was purified by column
chromatography with a mixture of CH Cl and MeOH (5%) to
give the pure triazole product as a yellow solid (220 mg,
2 4
SO , and evaporated under
(
400 MHz, MeOD) δ 8.83 (t, J ) 5.9, 1H), 8.15 (s, 1H, isomer
A), 8.14 (s, 1H, isomer B), 8.00-7.91 (m, 1H), 7.82 (s, 1H),
.60 (d, J ) 7.9, 1H), 7.39 (dd, J ) 13.2, 6.6, 1H), 6.38 (td, J
6.6, 2.2, 1H), 5.40 (dt, J ) 9.4, 4.9, 1H), 4.78 (d, J ) 17.0,
H), 4.69 (d, J ) 17.0, 1H), 4.52 (d, J ) 16.5, 1H), 4.40-4.31
m, 1H, isomer B), 4.36 (d, J ) 16.5, 1H), 4.17-4.05 (m, 1H,
isomer A), 3.84 (dd, J ) 12.1, 3.3, 1H, isomer B), 3.79 (dd, J
2
2
7
)
1
1
5
7
(
4
1
2
1
1
1
5%). H NMR (CD
3
OD) δ 8.53 (d, J ) 4.5, 1H), 7.96 (s, 1H),
.86-7.77 (m, 2H), 7.48 (d, J ) 7.8, 1H), 7.33 (m, 1H), 6.17
(
t, J ) 6.6, 1H), 4.69 (t, J ) 5.6, 2H), 4.38 (t, J ) 5.6, 2H),
.37 (m, 1H), 3.96 (s, 4H), 3.87 (q, J ) 3.4, 1H), 3.78 (dd, J )
)
12.2, 3.3, 1H, isomer A), 3.70 (dd, J ) 12.1, 3.1, 1H, isomer
2.0, 3.1, 1H), 3.71 (dd, J ) 12.0, 3.7, 1H), 2.26-2.11 (m,
B), 3.60 (dd, J ) 12.2, 3.2, 1H, isomer A), 2.90-2.80 (m, 1H,
isomer A), 2.72 (ddd, J ) 14.4, 8.3, 6.4, 1H, isomer A), 2.63
1
3
H), 1.84 (s, 3H) ppm. C NMR (CD OD) δ 165.20, 159.35,
3
52.25, 150.18, 146.37, 138.93, 136.91, 125.44, 124.40, 124.12,
10.58, 89.06, 87.36, 72.07, 62.84, 53.95, 44.26, 42.13, 41.52,
(
dd, J ) 14.0, 7.2, 1H, isomer B), 2.48 (ddd, J ) 14.1, 6.4,
13
4
1
1
3
.8, 1H, isomer B), 1.90 (s, 3H) ppm. C NMR (CD OD) δ
8.52, 13.22 ppm. High res. MS (ESI) m/z 458.2149
66.27, 161.70, 153.16, 151.89, 150.24, 140.91, 137.97, 126.77,
24.37, 124.07, 111.80, 86.69, 86.48, 85.91, 85.65, 63.87, 63.45,
+
[
C
21
H
27
N
7
O
5
]H (calc. 458.2146).
Rhenium Complexes. Tricarbonyl rhenium complexes were
synthesized according to the following general procedure: 1
equiv of thymidine containing ligand and 1 equiv of
63.15, 62.27, 62.00, 52.77, 39.16, 38.39, 12.19 ppm. High res.
+
MS (ESI) m/z 684.1214 [C22
H
23
1
N
7
O
7
Re] (calc. 684.1212).
[
Re(CO)
3
12]. (55 mg, 95%). H NMR (CD
3
OD) δ 8.08 (s,
[
ReBr
and water to form a 0.1 M solution. In the reactions with ligands
and 14, the pH of the reaction mixture was adjusted to 7 with
aqueous NEt
3 3 4 2
(CO) ][NEt ] were dissolved in a 1:1 mixture of MeOH
1
5
(
3
4
1
1
8
H), 7.85 (s, 1H), 6.20 (t, J ) 6.6, 1H), 5.91-5.77 (m, 1H),
.15 (d, J ) 11.2, 1H), 4.78 (m, 2H), 4.48-4.34 (m, 2H), 4.08
9
m, 1H), 3.92 (m, J ) 3.3, 1H), 3.80 (dd, J ) 12.0, 3.0, 1H),
4
OH. The reaction was stirred at 50 °C for 2 h and
.73 (dd, J ) 12.0, 3.8, 1H), 3.38 (m, 1H), 3.27 (dd, J ) 17.6,
followed by HPLC. The solvents were removed under vacuum
and the residue was purified by solid phase extraction using a
Sep-Pak column and a water-MeOH gradient to give the
.3, 1H), 2.39 (ddd, J ) 13.6, 5.9, 3.6, 1H), 2.24-2.18 (m,
13
H), 1.89 (s, 3H) ppm. C NMR (DMSO) δ 198.26, 197.44,
96.44, 180.16, 162.49, 150.18, 142.22, 135.08, 126.16, 108.26,
7.38, 84.99, 69.95, 61.07, 50.69, 50.60, 48.57, 48.05, 25.97,
Re(CO)
3
complex as a white or off-white powder.
1
[
Re(CO)
3
7]. (41 mg, 59%). H NMR (CD
3
OD) δ 8.20 (s,
12.84 ppm. High res MS (ESI) m/z 695.1106
+
1
5
(
3
H), 7.86 (s, 1H), 6.44 (t, J ) 6.4, 1H), 5.90 (dd, J ) 11.0,
[C20
H
23
N
6
O
10Re]H (calc. 695.1107).
.8, 1H), 5.58-5.44 (m, 1H), 5.18 (d, J ) 11.4, 1H), 4.45-4.32
1
[
Re(CO)
3
13]Br. (20 mg, 74%). H NMR (CD
3
OD) δ 8.26
m, 1H), 4.11 (d, J ) 3.9, 1H), 3.92 (dd, J ) 12.2, 2.9, 1H),
(
s, 1H), 8.22 (s, 1H), 7.88 (d, J ) 0.9, 1H), 7.87 (d, J ) 0.9,
.81 (dd, J ) 12.2, 3.1, 1H), 3.38 (dd, J ) 16.0, 1H), 3.26 (dd,
1
5
4
4
1
6
H), 6.27-6.22 (m, 1H), 6.21 (t, J ) 6.5, 1H), 5.43 (bs, 1H),
.37 (bs, 1H), 4.87-4.79 (m, 2H), 4.79-4.69 (m, 2H),
.55-4.47 (m, 2H), 4.47-4.42 (m, 2H), 4.43-4.36 (m, 2H),
.34 (dd, J ) 7.6, 4.5, 1H), 4.30 (d, J ) 3.5, 1H), 4.20 (d, J )
1.3, 1H), 4.16 (d, J ) 11.2, 1H), 4.10 (bs, 2H), 3.93 (dd, J )
.6, 3.3, 1H), 3.91 (dd, J ) 6.7, 3.4, 1H), 3.81 (t, J ) 2.8, 1H),
13
J ) 4.2, 1H), 3.02-2.73 (m, 2H), 1.91 (s, 3H) ppm. C NMR
CD OD) δ 197.39, 196.67, 184.57, 166.45, 152.22, 144.06,
38.43, 126.48, 111.81, 86.97, 85.89, 62.30, 62.01, 52.78, 38.68,
7.39, 12.19 ppm. High res. MS (ESI) m/z 651.0846
(
1
2
3
+
[
C
18
H
19
N
6
O
9
Re]H (calc. 651.0844).
1
[
Re(CO)
3
8]Br. (17 mg, 61%). H NMR (CD
3
OD) δ 8.41 (s,
3.78 (t, J ) 2.7, 1H), 3.76-3.72 (m, 1H), 3.72-3.68 (m, 1H),
3.05-2.88 (m, 3H), 2.88-2.76 (m, 2H), 2.76-2.61 (m, 1H),
2.47 (m, 1H), 2.41-2.29 (m, 1H), 2.27-2.19 (m, 4H), 1.88 (s,
1
1
4
H), 7.88 (s, 1H), 6.48 (t, J ) 6.3, 1H), 5.55 (m, 1H), 5.32 (bs,
H), 4.60 (bs, 1H), 4.53 (d, J ) 17.2, 1H), 4.56-4.47 (m, 1H),
.24 (d, J ) 17.2, 1H), 3.93 (dd, J ) 12.0, 3.1, 1H), 3.86 (dd,
3H), 1.87 (s, 3H) ppm. 13C NMR (CD
OD) δ 165.44 (165.29),
152.51, 151.23 (150.97), 137.22 (137.04), 126.03 (125.90),
3
J ) 12.0, 1H), 3.04-2.96 (m, 1H), 2.95-2.87 (m, 1H), 2.92