Synthesis of novel polyethers in a geometrically precise conformation

Organic Letters

Volumn 1, Issue 5, 1999, Pages 725-728

  Rodríguez, Rosa M ^a   Morales, Ezequiel Q ^a   Delgado, Mercedes ^a   Espínola, Carmen G ^a   Alvarez, Eleuterio ^a   Pérez, Ricardo ^a   Martin, Julio D ^a  

^a INSTITUTO DE INVESTIGACIONES QUÍMICAS   (Spain)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0039596263     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol990618h     Document Type: Article

References (40)

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4. (d) Maguire, G. E. M.; Meadows, E. S.; Murray, C. L.; Gokel, G. W. Tetrahedron Lett. 1997, 38, 6339-6342.
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11. + ions: (a) Doyle, D. A.; Morais-Cabral, J.; Pfuetzner, R. A.; Kuo, A.; Gulbis, J. M.; Cohen, S. L.; Chait, B. T.; MacKinnon, R. Science 1998, 280, 69-77.
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14. Reviews related to synthetic models for transmembrane channels: (a) Gokel, G. W.; Murillo, O. Acc. Chem. Res. 1996, 29, 425-432.
15. (b) Fyles, T. M.; Straaten-Nijenhuis, W. F. In Comprehensive Supramolecular Chemistry: Atwood, J. L., Davies, J. E. D., MacNichol, D. D., Vögtle, F., Reinhoudt, D. N., Eds.; Pergamon: Oxford, U.K., 1996; Vol. 10, pp 53-77.
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18. The reason for using crown ether homologues as the pore-forming moieties is the fact that their binding ability can be engineered to specific needs. Thus, the cavity diameter 5.5(5.9)-7.8(7.6) Å of the selected macroring in 2 and its weaker binding efficiency in comparison with 18-crown-6 analogues (see the Supporting Information) should allow for the transport of a wide variety of metal ions.
19. (a) Köning, B.; Horn, C. Synlett 1996, 1013-1014.
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23. For a different approach to the synthesis of lactone 8, see: Zheng, W.; De Mattei, J. A.; Wu, J.-P.; Duan, J. J.-W.; Cook, L. R.; Oinuma, H.; Kishi, Y. J. Am. Chem. Soc. 1996, 118, 7946-7968.
24. Compound 9 was prepared from triacetyl-D-glucal according to the described procedure: Nicolaou, K. C.; Hwang, C.-K.; Marron, B. E.; De Frees, S. A.; Coulados, E. A.; Abe, Y.; Carroll, P. J.; Snyder, J. P. J. Am. Chem. Soc. 1990, 112, 3040-3054.
25. The exclusive selection of one of the possible conformations for spiroacetal 23 is a consequence of the stabilizing anomeric and exo-anomeric effects that direct both C-O bonds to axial positions on the respective rings. For a review, see: Perron, F.; Albizati, K. J. Chem. Rev. 1989, 89, 1617-1661.
26. Ley, S. V.; Norman, J.; Griffith, W. P.; Marsden, S. P. Synthesis 1994, 639-666.
27. Applications involving reductive cleavage of the anomeric center in spiroacetals have only recently been recognized for their potential synthetic utility. For recent examples, see: (a) Crimmins, M. T.; Rafferty, S. W. Tetrahedron Lett. 1996, 32, 5649-5652.
28. (b) Oikawa, M.; Veno, T.; Oikawa, H.; Ichihara, A. J. Org. Chem. 1995, 60, 5048-5068.
29. This is done by minimizing the individual structures by an MM3* force field implemented in the MacroModel V6.0 program. Mohamadi, F.; Richards, N. G. J.; Guida, W. C.; Liskamp, R.; Lipton, M.; Caulfield, C.; Chang, G.; Hendrikson, T.; Still, W. C. J. Comput. Chem. 1990, 11, 440-447.
30. Calculated coupling constants for diacetate 4 (R = Ac) gave better agreement with the experimental values than did those constants for free hydroxyl groups: Haasnot, C. A. G.; De Leeuw, F. A. M.; Altona, C. Tetrahedron 1980, 36, 2783-2792.
31. Monte Carlo calculations were made, yielding a set of 192 conformers (see the Supporting Information).
32. Simulations were done using gNMR 6.3.5 from Cherwell Scientific Publishing Ltd., The Magdalen Centre, Oxford Science Park, Oxford 0X4 4GA, U.K.
33. Analysis of the spectra were made using TRIAD 6.3 as part of the package SYBYL 6.3 from Tripos Inc. (Supporting Information).
34. The NMR characteristic observed for 2 and 3 were virtually superimposable on those of the relevant protons and carbons.
35. As is the case for all ring-forming reactions, the RCM of polyoxy-ethylene rings is determined by several factors, including the kinetics of ring closing, ring strain, and competing metathesis-based polymerization. In the case of compound 3 (2R,3S,2′R,2″S,4″aR,8″aS) the RCM to give 2 occurs due to the favored preorganization of the C-linked oxanyl system, which allows close proximity of the terminal olefins. All attempts to prepare diastereomers of 2 by RCM of diastereomers of 3, 3a (2R,3S,2′S,2″S, 4″aR,8″aS), 3b (2S,3R,2′R,2″S,4″aR,8″aS), and 3c (2S,3R,2′S,2″S,4″aR,8″aS), were unsuccessful. This gathered information was of crucial importance in the selection of the target unit subject of the present communication.
36. Coveney, P. V.; Emerton, A. N.; Boghosian, B. M. J. Am. Chem. Soc. 1996, 118, 10719-10724.
37. Although this computer modeling was the basis for the selection of the "building block" 2, rigorous testing will be required to determine whether the design lives up to its expectations as an ion channel agent.
38. HOLE suite of programs. Smart, O. S.; Goodfellow, J. M.; Wallace, B. A. Biophys. J. 1993, 65, 2455-2460.
39. Calculations were done by fixing the backbone of the oligomer, allowing only the movement of the atoms forming the cyclic ether ring. MMFF 94 was used with our standard conditions (Supporting Information).
40. Abbreviations: TBS = tert-butyldimethylsilyl; MEM = methoxy-methyl; DMSO = dimethyl sulfoxide; KHMDS = potassium bis(trimethylsilyl)amide; DIBALH = diisobutylaluminum hydride; MS = molecular sieves; 4-DMAP = 4-(dimethylamino)pyridine; NMO = 4-methylmorpholine N-oxide; TBAF = tetra-n-butylammonium fluoride; PCC = pyridinium chlorochromate; CSA = 10-camphorsulfonic acid; TPAP = tetra-n-propylammonium perruthenate.