A. Leydier et al. / Tetrahedron 64 (2008) 11319–11324
11323
residue was purified by silica gel column chromatography (EtOAc/
dryness to give 7a (735 mg, 98%) as grey foam. 1H NMR (CDCl3,
300 MHz, 25 ꢂC)
(ppm): 8.31 (br s, 2H, NH), 7.26 (m, 2H, Ar–H),
cyclohexane 3:1) to give 5b (2.27 g, 63%) as white foam. 1H NMR
d
(CDCl3, 300 MHz, 25 ꢂC)
d
(ppm): 8.64 (br s, 2H, NH), 7.52 (m, 4H,
6.87–7.03 (m, 10H, Ar–H), 6.41 (m, 2H, Ar–H), 4.09 (AB d, 4H,
2J(H,H)¼12.8 Hz, Ar–CH2–Ar ax), 3.97 (m, 4H, O–CH2–CH2–NH),
3.59 (m, 4H, O–CH2–CH2–NH2), 3.36 (AB d, 4H, 2J(H,H)¼12.8 Hz, Ar–
CH2–Ar eq),1.17 (s,18H, (CH3)3C unsubst. rings),1.01 (s,18H, (CH3)3C
Ar–H), 7.35 (m, 6H, Ar–H), 6.96 (m, 6H, Ar–H), 6.79 (s, 4H, Ar–H),
6.48 (m, 2H, Ar–H), 6.21 (m, 2H, Ar–H), 5.34 (s, 4H, O–CH2–Ar), 4.26
(m, 8H, O–CH2–CH2–NH and Ar–CH2–Ar ax), 3.70 (m, 4H, O–CH2–
CH2–NH2), 3.28 (AB d, 4H, 2J(H,H)¼13.2 Hz, Ar–CH2–Ar eq), 1.25 (s,
18H, (CH3)3C unsubst. rings), 0.98 (s, 18H, (CH3)3C subst. rings).
subst. rings). 13C NMR (CDCl3, 75 MHz, 25 ꢂC)
d (ppm): 171.1 (C]O),
150.1 (ArC), 149.7 (ArC), 148.8 (ArC), 146.5 (ArC), 143.6 (ArC), 136.3
(ArC), 133.3 (ArC), 129.4 (ArCH), 128.6 (ArCH), 127.9 (ArC), 126.7
(ArCH), 126.3 (ArCH), 126.0 (ArCH), 118.8 (ArCH), 117.7 (ArCH), 114.5
(ArC), 75.0 (CH2), 39.9 (CH2), 34.7 (Cq), 34.4 (Cq), 32.8 (CH2), 32.2
(CH3), 31.6 (CH3). HR ESIMS calculated for C62H74N2O10Naþ¼
1029.5241; found¼1029.5242. Anal. Calcd (%) for C62H74N2O10: C,
73.93; H, 7.41; N, 2.78; O, 15.88. Found: C, 73.92; H, 7.66, N 2.54.
13C NMR (CDCl3, 75 MHz, 25 ꢂC)
d (ppm): 161.4 (C]O), 158.9 (C]O),
149.7 (ArC), 149.0 (ArC), 148.1 (ArC), 143.7 (ArC), 143.0 (ArC),
138.1 (ArCH), 134.0 (ArC), 132.7 (ArC), 130.7 (ArCH), 129.8 (ArCH),
129.0 (ArCH), 127.7 (ArC), 126.3 (ArCH), 125.8 (ArCH), 123.7 (ArCH),
105.7 (ArCH), 80.0 (CH2), 74.8 (CH2), 40.0 (CH2), 34.4 (Cq), 34.2 (Cq),
32.2 (CH2), 32.0 (CH3), 31.4 (CH3). HR ESIMS calculated for
C74H84N4O10Naþ¼1211.6085; found¼1211.6084. Anal. Calcd (%) for
C74H84N4O10: C, 74.72; H, 7.12; N, 4.71; O, 13.45. Found: C, 74.76; H,
7.25; N, 4.54.
4.9. Synthesis of 1,3-CalixHOPO 7b
5,11,17,23-Tetra-tert-butyl-25,27-(2-(1-benzyloxy-2-oxo-1,2-dih
ydropyridine-6-carboxamido)ethyl)-26,28-dihydroxycalix[4]arene
(884 mg, 0.876 mmol) was added in 25 ml 32% HCl in 65 ml acetic
acid. After a week under stirring, the mixture was evaporated,
100 ml were added. The mixture was washed with CH2Cl2
(3ꢁ50 ml). The combined organic layers were washed with water
(3ꢁ50 ml), brine (50 ml), then dried over MgSO4 and evaporated to
dryness to give 7b (617 mg, 70%) as orange powder. 1H NMR (CDCl3,
4.6. Synthesis of 1,3-CalixCAM 6a
25,27-(2-(2,3-Bis(benzyloxy)-1-carboxamido)ethyl)-26,28-dihy
droxycalix[4]arene (0.47 g, 0.41 mmol) and 70 mg of Pd/C (5%) in
20 ml of THF was stirred under 1 atm of H2. After 96 h, the mixture
was filtered on Celite, evaporated to dryness to give 6a (315 mg,
97%) as grey foam. 1H NMR (CDCl3, 300 MHz, 25 ꢂC)
d (ppm): 12.53
(br s, Ar–OH), 8.31 (br s, 2H, NH), 8.23 (br s, 2H, Ar–OH), 7.19 (m, 2H,
Ar–H), 6.68–7.04 (m, 14H, Ar–H), 6.38 (m, 2H, Ar–H), 4.01–4.12 (m,
8H, O–CH2–CH2–NH and Ar–CH21–3Ar ax), 3.36–3.43 (m, 8H, O–CH2–
CH2–NH2 and Ar–CH2–Ar eq). C NMR (CDCl3, 75 MHz, 25 ꢂC)
300 MHz, 25 ꢂC)
d (ppm): 6.89–7.23 (m, 3H, ArH), 7.01 (s, 4H, Ar–H),
6.75 (s, 4H, Ar–H), 4.06–4.21 (m, 12H, O–CH2–CH2–NH and Ar–CH2–
Ar ax), 3.29 (AB d, 4H, 2J(H,H)¼13.2 Hz, Ar–CH2–Ar eq), 1.28 (s, 18H,
(CH3)3C unsubst. rings), 0.93 (s, 18H, (CH3)3C subst. rings). 13C NMR
d
(ppm): 171.0 (C]O), 152.2 (ArC), 150.5 (ArC), 146.5 (ArC), 133.5
(CDCl3, 75 MHz, 25 ꢂC)
d (ppm): 160.2 (C]O), 157.3 (C]O), 150.2
(ArC), 129.9 (ArCH), 129.5 (ArCH), 128.2 (ArC), 127.0 (ArCH), 125.9
(ArCH), 121.1 (ArCH), 119.1 (ArCH), 118.6 (ArCH), 117.4 (ArCH), 114.5
(ArC), 75.0 (CH2), 39.9 (CH2), 32.1 (CH2). HR ESIMS calculated for
C46H42N2O10Naþ¼805.2737; found¼805.2736. Anal. Calcd (%) for
C46H42N2O10$4*H2O: C, 64.63; H, 5.90; N, 3.28; O, 26.20. Found: C,
64.92; H, 5.83, N 3.05.
(ArC), 149.6 (ArC), 147.9 (ArC), 142.6 (ArC),135.1 (ArCH), 132.7 (ArC),
128.2 (ArC), 126.2 (ArCH), 126.1 (ArCH), 125.6 (ArCH), 117.3 (ArCH),
112.2 (ArCH), 74.5 (CH2), 40.4 (CH2), 34.3 (Cq), 34.2 (Cq), 32.1 (CH2),
32.0 (CH3), 31.4 (CH3). HR ESIMS calculated for C60H72N4O10
Naþ¼1031.5146; found¼1031.5145. Anal. Calcd (%) for C60H72N4O10
:
C, 71.40; H, 7.19; N, 5.55; O, 15.85. Found: C, 71.61; H, 7.32; N, 5.21.
4.7. Synthesis of 1,3-CalixHOPO 6b
4.10. Synthesis of 1,3-CalixCAMS 8a
25,27-(2-(1-Benzyloxy-2-oxo-1,2-dihydropyridine-6- carboxami
do)ethyl)-26,28-dihydroxycalix[4]arene (0.85 mg, 0.888 mmol) was
added in 30 ml 32% HCl in 60 ml acetic acid. After 96 h under stir-
ring, the mixture was evaporated, 100 ml were added. The mixture
was washed with CH2Cl2 (3ꢁ50 ml). The combined organic layers
were washed with water (3ꢁ50 ml), brine (50 ml), then dried over
MgSO4 and evaporated to dryness to give 6b (603 mg, 87%) as yel-
25,27-(2-(N-(2,3-Bis(hydroxy)-1-benzamido))ethyl)-26,28-dihy
droxycalix[4]arene (106 mg, 0.135 mmol) in H2SO4 (2 ml) was
stirred at 50 ꢂC for 16 h. The mixture was then allowed to cool to
room temperature, poured in Et2O (50 ml). The resulting pre-
cipitate was filtered off under argon and dried under vacuum to
give 8a as a hygroscopic brown powder (140 mg, 82%). 1H NMR
(D2O, 300 MHz, 25 ꢂC)
d
(ppm): 7.26 (d, J¼1.9 Hz, 2H, Ar–H), 7.49 (s,
low foam. 1H NMR (DMSO-d6, 300 MHz, 25 ꢂC)
d (ppm): 9.13 (br s,
4H, Ar–H), 7.24 (s, 4H, Ar–H), 7.14 (d, J¼1.9 Hz, 2H, Ar–H), 4.23 (t,
J¼4.2 Hz, 4H, O–CH2–CH2–N), 4.13 (t, J¼4.2 Hz, 4H, O–CH2–CH2–N),
4.05 (AB d, 4H, 2J(H,H)¼13.8 Hz, Ar–CH2–Ar ax), 3.48 (AB d, 4H,
2H, Ar–OH), 8.06 (s, 2H, NH), 7.26 (m, 2H, Ar–H), 7.11 (d, J¼7.5 Hz,
4H, Ar–H), 7.06 (d, J¼7.5 Hz, 4H, Ar–H), 6.77 (m, 2H, Ar–H), 6.48–
6.56 (m, 4H, Ar–H), 6.42 (d, J¼6.9 Hz, 2H, Ar–H), 4.17 (AB d, 4H, 2J
(H,H)¼13.0 Hz, Ar–CH2–Ar ax), 4.06 (m, 4H, O–CH2–CH2–NH), 3.80
(d, J¼5.4 Hz, 4H O–CH2–CH2–NH), 3.25 (AB d, 4H, 2J(H,H)¼13.0 Hz,
Ar–CH2–Ar eq).
2J(H,H)¼13.8 Hz, Ar–CH2–Ar eq). C NMR (D2O, 75 MHz, 25 ꢂC)
13
d
(ppm): 169.8 (C]O), 155.2 (ArC), 153.9 (ArC), 148.8 (ArC), 145.1
(ArC), 139.8 (ArC), 134.2 (ArC), 133.7 (ArC), 133.5 (ArC), 127.4 (ArC),
127.0 (ArCH), 126.9 (ArCH), 126.7 (ArCH), 117.8 (ArC), 117.2 (ArCH),
115.3 (ArCH), 74.4 (CH2), 40.1 (CH2), 31.0 (CH2). HR ESIMS calculated
for C46H42N2O28S6Naþ¼1285.0141; found¼1285.0136. Anal. Calcd
(%) for C46H42N2O28S6$6*H2O: C, 40.29; H, 3.97; N, 2.04; O, 39.67; S,
14.03. Found: C, 39.98; H, 4.12; N, 1.79.
13C NMR (CDCl3, 75 MHz, 25 ꢂC)
d (ppm): 160.6 (C]O), 158.0
(C]O), 153.0 (ArC), 151.5 (ArC), 138.5 (ArC), 135.4 (ArCH), 133.2
(ArC), 129.6 (ArCH), 129.1 (ArCH), 128.3 (ArC), 126.1 (ArCH), 120.0
(ArCH),117.9 (ArCH), 111.8 (ArCH), 74.8 (CH2), 40.4 (CH2), 31.7 (CH2).
HR ESIMS calculated for C44H40N4O10Naþ¼807.2642; found¼
807.2644. Anal. Calcd (%) for C44H40N4O10: C, 67.34; H, 5.14; N, 7.14;
O, 20.39. Found: C, 67.38; H, 5.38; N, 6.85.
Acknowledgements
4.8. Synthesis of 1,3-CalixCAM 7a
We thank Dr. Bouchu, Genevieve Herault and Marie-Christine
Duclos for analytical assistance. This work was supported by
a program of interdisciplinary research called ‘Nuclear and Envi-
5,11,17,23-Tetra-tert-butyl-25,27-(2-(2,3-bis(benzyloxy)-1- carb
oxamido)ethyl)-26,28-dihydroxycalix[4]arene (1.027 g, 0.75 mmol)
and 200 mg of Pd/C (5%) in 25 ml of THF was stirred under 1 atm of
H2. After 96 h, the mixture was filtered on Celite, evaporated to
`
ronmental Toxicology, Tox-Nuc-E’ funded by the Commissariat a
´
l’Energie Atomique (CEA) and Comite National pour la Recherche
Scientifique (CNRS).