Z. Zhang et al. / Tetrahedron 63 (2007) 11716–11723
11721
8H), 7.49–7.54 (m, 3H), 7.18 (d, 2H, J¼7.6 Hz), 7.11 (d, 2H,
J¼7.6 Hz), 4.65 (s, 4H), 4.44 (s, 4H), 3.34 (t, 4H, J¼7.2 Hz),
2.92 (s, 2H), 2.37 (m, 4H), 1.40–1.51 (m, 4H), 1.35 (s, 9H);
13C NMR (CDCl3): 170.3, 155.9, 155.3, 147.9, 137.7, 133.7,
133.4, 131.8, 130.6, 124.1, 121.7, 121.0, 80.9, 54.7, 53.6,
52.6, 50.9, 46.8, 28.1, 26.0. HRMS (FAB+): required for
C44H49N9O14S3+H 1024.2594, found 1024.2639.
4.42 (s, 4H), 4.28 (t, 2H, J¼6.0 Hz), 3.49 (t, 2H, J¼6.0 Hz),
3.42 (t, 4H, J¼7.2 Hz), 3.02 (s, 2H), 2.59 (t, 4H, J¼7.2 Hz),
2.03–2.09 (m, 2H); 13C NMR (CDCl3): 170.2, 167.0, 156.9,
155.6, 149.1, 147.9, 137.9, 136.9, 133.7, 132.7, 132.0,
131.8, 130.7, 124.2, 124.0, 122.0, 121.6, 121.3, 120.6,
107.4, 66.5, 58.6, 53.4, 53.2, 52.5, 45.9, 36.5, 28.8. MS
(FAB+): m/z 1228.3 (M+1, 10%). HRMS (FAB+): required
for C56H53N13O14S3+H 1228.3044, found 1228.3075.
3.8. (3,7,13-Tris(2-nitrobenzenesulfonyl)-1,5(2,6)-dipyr-
idina-3,7,10,13-tetrazacyclotetradecaphane)-10-acetic
acid (10a)
3.11. 11-{3-Aza-2-oxo-6-[(2,20:60,200-terpyridin-40-yl)-
oxy]hexyl}-3,7,15-tris(2-nitrobenzenesulfonyl)-1,5(2,6)-
dipyridina-3,7,11,15-tetrazacyclohexadecaphane (11b)
To a solution of 9a (600 mg, 0.6 mmol) in CH2Cl2 (8 ml),
TFA (8 ml) was added dropwise at 0 ꢀC. The mixture was
stirred at room temperature for another 6 h, after which the
mixture was evaporated in vacuo. The residue was dissolved
in methanol (10 ml) and saturated NaHCO3 was added to
neutralize the acid. The mixture was extracted several times
with CH2Cl2. The organic phase was dried (anhydrous
Na2SO4) and concentrated affording the crude solid. After
purification by silica gel chromatography, the compound
was obtained quantitatively as white solid. 1H NMR
(CDCl3): 8.05 (d, 2H, J¼6.4 Hz), 7.64–7.94 (m, 12H),
7.23 (d, 2H, J¼6.0 Hz), 7.17 (d, 2H, J¼6.0 Hz), 4.69 (s,
4H), 4.67 (s, 4H), 3.91 (br, 4H), 3.83 (s, 2H), 3.44 (br,
4H); 13C NMR (CDCl3): 205.8, 155.7, 148.2, 137.9, 134.3,
132.9, 132.3, 132.0, 130.3, 124.2, 121.7, 121.4, 54.2, 53.1,
52.7, 51.6, 47.0. MS (FAB+): m/z 940 (M+H, 10%).
HRMS (FAB+): required for C38H36N9O14S3+H 940.1690,
found 940.1700.
Compound 11b was obtained as a yellow foam in 86% yield,
as described for compound 11a. 1H NMR (CDCl3): 8.63–8.55
(m, 3H), 7.77–7.89 (m, 6H), 7.43–7.65 (m, 12H), 7.15–7.33
(m, 7H), 4.68 (s, 4H), 4.35 (s, 4H), 4.19 (t, 2H, J¼7.2 Hz),
3.24–3.42 (m, 6H), 2.99 (s, 2H), 2.40 (br, 4H), 2.20 (t, 2H,
J¼7.2 Hz), 1.62 (br, 4H); 13C NMR (CDCl3): 166.9, 156.9,
155.8, 155.3, 149.0, 147.8, 137.9, 137.0, 133.8, 133.6,
132.9, 131.8, 130.7, 128.3, 126.1, 125.1, 124.0, 121.9,
121.5, 121.2, 66.2, 58.0, 53.5, 52.8, 52.3, 46.6, 36.5, 28.9,
25.2. MS (FAB+): m/z 1255 (M+1, 10%). HRMS: required
for C58H56N13O14S3+H 1256.3455, found 1256.3388.
3.12. 10-{3-Aza-2-oxo-6-[(2,20:60,200-terpyridin-40-yl)-
oxy]hexyl}-1,5(2,6)-dipyridina-3,7,10,13-tetrazacyclo-
tetradecaphane (12a)
Thiophenol (265 mg, 2.40 mmol) was added to a stirred
mixture of compound 11a (586 mg, 0.48 mmol) and anhy-
drous K2CO3 (1.110 g, 8.04 mmol) in 10 ml of anhydrous
DMF. The resulting mixture was stirred overnight at room
temperature. The solvent was evaporated and the residue
was partitioned between water and CH2Cl2. The organic
phase was separated and the aqueous phase was extracted
with CH2Cl2. The combined organic phases were washed
with brine, dried (Na2SO4) and concentrated to a syrup,
which was purified on silica gel applying stepwise elution:
CH2Cl2, CH2Cl2/MeOH (20:1; v/v), MeOH, MeOH/concd
aq NH3 (30:1; v/v). Compound 12a was obtained in 85%
yield (273 mg) as pale yellow solid foam. 1H NMR
(DMSO-d6): 8.74–8.75 (m, 2H), 8.62–8.65 (m, 2H), 8.01–
8.05 (m, 2H), 7.88 (s, 2H), 7.73 (t, 2H, J¼7.6 Hz), 7.47–
7.53 (m, 2H), 7.18–7.24 (m, 4H), 4.11 (s, 4H), 4.09 (s,
4H), 3.51–3.72 (s, 8H), 3.11–3.34 (m, 4H), 2.60–2.78 (m,
6H), 2.35–2.43 (m, 2H), 1.66–1.69 (m, 2H); 13C NMR
(DMSO-d6): 174.9, 166.9, 159.1, 157.2, 155.3, 149.8,
139.1, 137.9, 128.3, 125.1, 124.3, 121.3, 120.9, 107.1,
66.0, 57.7, 54.0, 53.6, 47.3, 40.6, 36.6, 28.4. MS (FAB+):
m/z 710 (M+K, 30%), 747 (M+2K, 100%). HRMS
(FAB+): required for C38H43N10O2+H 673.4016, found
673.4039.
3.9. (3,7,15-Tris(2-nitrobenzenesulfonyl)-1,5(2,6)-dipyr-
idina-3,7,11,15-tetrazacyclohexadecaphane)-11-acetic
acid (10b)
Compound 10b was obtained quantitatively as white solid,
as described for compound 10a. H NMR (CD3COCD3):
1
8.00–8.05 (m, 3H), 7.77–7.82 (m, 8H), 7.68–7.76 (m, 3H),
7.21–7.26 (m, 4H), 4.78 (s, 4H), 4.47 (s, 4H), 3.46 (br,
4H), 3.31 (br, 2H), 2.78 (br, 4H), 1.77 (br, 4H); 13C NMR
(CD3COCD3): 205.8, 156.1, 155.7, 148.1, 137.9, 134.2,
133.3, 132.2, 130.6, 124.2, 121.8, 121.3, 56.2, 54.1, 52.5,
51.0, 47.6, 24.9. MS (FAB+): m/z 968 (M+H, 10%).
HRMS (FAB+): required for C40H41N9O14S3+H 968.2010,
found 968.2013.
3.10. 10-{3-Aza-2-oxo-6-[(2,20:60,200-terpyridin-40-yl)-
oxy]hexyl}-3,7,13-tris(2-nitrobenzenesulfonyl)-1,5(2,6)-
dipyridina-3,7,10,13-tetrazacyclotetradecaphane (11a)
To a solution of compound 10a (259 mg, 0.276 mmol) in dry
DMF (6 ml), dicyclohexylcarbodiimide (DCC, 56.8 mg,
0.275 mmol) and 1-hydroxybenzotriazole (1-HOBt,
37.2 mg, 0.275 mmol) were added. The reaction mixture
was stirred at room temperature for 1 h and compound 7
(84.2 mg, 0.275 mmol) was added. The reaction mixture
was stirred for 72 h, after which the precipitate was filtered
off. The filtrate was concentrated in vacuo affording the crude
product. After silica gel chromatography (CH2Cl2/
MeOH¼20:1), 11awasobtainedasyellow foamin85% yield.
1H NMR (CDCl3): 8.66 (d, 2H, J¼4.4 Hz), 8.59 (d, 2H,
J¼8.0 Hz), 7.98 (s, 2H), 7.83–7.88 (m, 6H), 7.50–7.65 (m,
12H), 7.30–7.35 (m, 3H), 7.09–7.27 (m, 4H), 4.66 (s, 4H),
3.13. 11-{3-Aza-2-oxo-6-[(2,20:60,200-terpyridin-40-yl)-
oxy]hexyl}-1,5(2,6)-dipyridina-3,7,11,15-tetrazacyclo-
hexadecaphane (12b)
Compound 12b was obtained in the same way as for 12a in
1
85% yield. H NMR (DMSO-d6): 8.68 (d, 2H, J¼4.0 Hz),
8.59 (d, 2H, J¼8.0 Hz), 7.92–8.00 (m, 4H), 7.62–7.66
(m, 2H), 7.45–7.49 (m, 2H), 7.22 (d, 2H, J¼7.6 Hz), 7.15
(d, 2H, J¼7.6 Hz), 4.17 (t, 2H, J¼6.4 Hz), 3.80 (s, 8H),