S. Menuel et al. / Tetrahedron 63 (2007) 1706–1714
1713
4. De Jong, M. R.; Knegtel, M. A. R.; Grootenhuis, P. D. J.;
Huskens, J.; Reinhoudt, D. N. Angew. Chem., Int. Ed. 2002,
41, 1004–1008.
0.018 mmol) in H2O (25 mL) at rt. The mixture was stirred
18 h more and then lyophilised to yield a yellow amorphous
powder: [a]2D0 +83 (c 0.1, H2O); FTIR (KBr): n¼1642 cmꢀ1
5.09 (m, 14H, H-1 CDa,b); 4.42 (m, 4H, CH2 Busulfan);
4.08–3.93 (m, 14H, H-3 CDa,b); 3.94–3.78 (m, 36H,
H-6 CDa, H-5 CDa,b); 3.77–3.72 (m, 14H, CH2 crown);
3.71–3.52 (m, 40H, H-2 CDa,b, H-4 CDa,b, H-6 CDb, CH2
crown); 3.49–3.39 (m, 2H, CHb crown); 3.23 (s, 6H, CH3
Busulfan); 1.95 (m, 4H, CH2b Busulfan); 1.29–1.10 (m, 6H,
CH3 crown).
1
(C]O urea). H NMR (400 MHz, D2O, 25 ꢁC): d (ppm)
5. (a) Breslow, R.; Halfon, S.; Zhang, B. Tetrahedron 1995, 51,
377–388; (b) Breslow, R.; Zhang, B. J. Am. Chem. Soc. 1996,
118, 8495–8496; (c) De Jong, M. R.; Engbersen, J. F. J.;
Huskens, J.; Reinhoudt, D. N. Chem.—Eur. J. 2000, 6, 4034–
4040; (d) Venema, F.; Nelissen, H. F. M.; Berthault, P.;
Birlirakis, N.; Rowan, A. E.; Feiters, M. C.; Nolte, R. J. M.
Chem.—Eur. J. 1998, 4, 2237–2250; (e) Shiu, S. H.; Myles,
D. C.; Garell, R. L.; Stoddart, J. F. J. Org. Chem. 2000, 65,
2792–2796.
6. (a) Zhang, B.; Breslow, R. J. Am. Chem. Soc. 1997, 119,
1676–1681; (b) Sallas, F.; Marsura, A.; Petot, V.; Pinter, I.;
Kovacs, J.; Jicsinszky, L. Helv. Chim. Acta 1998, 81,
632–645; (c) Peirera Silva, M. J. J.; Haider, J. M.; Chavarot,
M.; Ashton, P. R.; Williams, R. M.; De Cola, L.; Heck, R.;
Marsura, A.; Pikramenou, Z. Supramol. Chem. 2003, 15,
563–571.
7. (a) Pikramenou, Z.; Nocera, D. G. Inorg. Chem. 1992, 31, 532–
536; (b) Pikramenou, Z.; Johnson, K. M.; Nocera, D. G.
Tetrahedron Lett. 1993, 34, 3531–3534.
8. To our knowledge, only two reports in the literature deal with
achiral azacrowns linked to CDs: (a) Suzuki, I.; Ito, M.; Osa,
T.; Anzai, J.-i. Chem. Pharm. Bull. 1999, 47, 151–155; (b)
Lock, J. S.; May, B. L.; Clements, P.; Lincoln, S. F.; Easton,
C. J. Org. Biomol. Chem. 2004, 2, 1381–1386.
9. (a) Wudl, F.; Gaeta, F. J. Chem. Soc., Chem. Commun. 1972,
107; (b) de Vries, E. F. J.; Steenwinkel, P.; Brusses, J.; Kruse,
C. G.; Van der Gen, A. J. Org. Chem. 1993, 58, 4315–4325;
(c) Zhu, X.-C.; Yan, H.; Chen, Y.-Y.; Wu, C.-Y.; Lu, X.-R.
J. Chromatogr., A 1996, 753, 269–277; (d) Joly, J.-P.;
4.4. Molecular modelling calculations
A coarse skeleton of the ether crown was initially prepared
using ChemDraw and Chem3D software packages19 and
the structure of the native b-CD (native b-CD) was taken
from the Cambridge Structural Database by means of
ConQuest 1.8.20 In order to build up the final ligand, two
CDs were attached through the urea groups to the ether
crown after removing one of their primary hydroxyl groups.
The molecular modelling calculations were carried out on
a Pentium-4 personal computer using the TINKER pro-
gramme and its implemented MM3 force field.21 The energy
minimisation MINIMIZE option of the TINKER pro-
gramme was first used to find a starting geometrical state
of the system. The respective conformational minima
were sought without constraints for the ligand in vacuum
(structure S1) and in water solvent (structure S2). Structure
S1 was minimised to a final RMS gradient equal to
0.0948 kJ Aꢀ1 molꢀ1 by a modified version of the algorithm
˚
of Jorge Nocedal based on a quasi-Newton method (596
cycles).22 No cut-off option was used in this case. The
structure S2 was obtained with the same method (final
€
Schroder, G. Tetrahedron Lett. 1997, 38, 8197–8198; (e) Joly,
J.-P.; Walker, O.; Mutzenhardt, P. Magn. Reson. Chem. 2001,
39, 212–214; (f) He, Y.; Xiao, Y.; Meng, L.; Zeng, Z.; Wu,
X.; Wu, C.-T. Tetrahedron Lett. 2002, 43, 6249–6253; (g)
Lobach, A. V.; Leus, O. N.; Titova, N. Y.; Luk’yanenko,
N. G. Russian J. Org. Chem. 2003, 39, 1037–1041; (h)
Correa, W. H.; Scott, J. L. Molecules 2004, 9, 513–519.
10. (a) Template Synthesis of Macrocyclic Compounds; Gerbeleu,
N. V., Arion, V. B., Burgess, J., Eds.; Wiley-VCH: Germany,
1999; (b) Menuel, S.; Joly, J.-P.; Marsura, A. Proceedings
of the 12th International Cyclodextrin Symposium; APGI:
Toulouse, France, 2004; pp 153–158; (c) Menuel, S.; Joly,
J.-P.; Marsura, A. E.S.F. Conference on Supramolecular
Chemistry, Obernay (Strasbourg), France, 2005.
RMS gradient equal to 0.0950 kJ Aꢀ1 molꢀ1 (1475
˚
3
˚
cycles)) considering a cubic box of 25ꢂ25ꢂ25 A contain-
ing 383 water molecules. In this case, the periodic boundary
˚
conditions were imposed with a cut-off radius of 9 A. A sto-
chastic annealing procedure (chosen temperature 1000 K,
time step 0.02 ps, 95 snapshots) applied to conformation
S2 gives very similar results showing the robustness of
the MINIMIZE method implemented in the TINKER
programme.
Acknowledgements
11. Porwanski, S.; Kryczka, B.; Marsura, A. Tetrahedron Lett.
2002, 43, 8441–8443.
Financial supports from the CNRS and the French ‘Minis-
ꢁ
tere de l’Education et de la Recherche’ are gratefully
acknowledged.
ꢀ
12. Charbonnier, F. Ph.D. thesis, University Henri Poincare, Nancy
1, France, 1999.
13. Galton, D. A. G. Lancet 1953, 1, 208–213.
14. Vassal, G.; Koscielny, S.; Challine, D.; Valteau-Couanet, D.;
Boland, I.; Deroussent, A.; Lemerle, J.; Gouyette, A.;
Hartmann, O. Cancer Chemother. Pharmacol. 1996, 37, 247–
253.
References and notes
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