Estramicins: A novel cyclic diyl precursor derived from estradiol

Tetrahedron Letters

Volumn 38, Issue 12, 1997, Pages 2179-2182

  Meert, Christel ^a   Wang, Jing ^a   De Clercq, Pierre J ^a  

^a GHENT UNIVERSITY   (Belgium)

Author keywords

[No Author keywords available]

Indexed keywords

ESTRADIOL; ESTRADIOL DERIVATIVE; ESTRAMICIN; UNCLASSIFIED DRUG;

ARTICLE; CYCLIZATION; DRUG SYNTHESIS; PRECURSOR; REACTION ANALYSIS;

EID: 0031585035     PISSN: 00404039     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4039(97)00276-1     Document Type: Article

References (43)

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21. 8. For a recent example of a conjugate involving a ten membered cyclic enediyne and diethylstilbestrol see Jones, G.B.; Huber, R.S.; Mathews, J.E.; Li, A. Tetrahedron Lett. 1996, 37, 3643-3646.
22. 9. For examples in which the enediyne system is generated by the elimination of a methanesulfonate see: (a). Audrain, H.; Skrydstrup, T.; Ulibarri, G.; Grierson, D.S. Synlett 1993, 20-22;
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24. For an account of the strategies for the generation of reactive enediynes from stable precursors see: (a). Maier, M.E. Kontakte 1994, 2, 3-17;
25. (b). Maier, M.E. Synlett. 1995, 13-26.
26. 10. Presumably under harsh basic conditions a fragmentation reaction involving cleavage of bond C17-C20 is occuring. We thank David S. Grierson for drawing our attention to this possibility.
27. 11. Ojasoo, T.; Raynaud, J.-P.; Mornon, J.-P. in Comprehensive Medicinal Chemistry, Vol. 3, (Eds.: Hansch, C.; Sammes, P.G.; Taylor, G.B.), Pergamon Press, 1990, p. 1175-1226.
28. 12. Kruithof, K.J.H.; Schmitz, R.F.; Klumpp, G.W. Tetrahedron 1983, 39, 3073-3081.
29. 3); 2.75 (2H, d, J=6.68 Hz); 0.97 (9H, s); 0.94 (3H, s); 0.90 (9H, s); 0.18 (6H, s), 0.14 (3H, s); 0.13 (3H, s) ppm for 10: 9.85 (1H,broad s); 7.12 (1H, d, J=8.46 Hz); 6.61 (1H, dd, J=8.43, 2.57 Hz); 6.54 (1H, d, J=2.50 Hz); 4.59 (1H, t, J=6.77 Hz); 0.97 (9H, s); 0.90 (9H, s); 0.89 (3H, s); 0.18 (15H, s); 0.14 (3H, s); 0.13 (3H, s) ppm for 11: 9.82 (1H, broad d, J=1.95 Hz); 7.11 (1H, d, J=8.49 Hz); 6.61 (1H, dd, J=8.45, 2.54 Hz); 6.54 (1H, d, J=2.46 Hz); 4.60 (1H, t, J=6.68 Hz); 2.63 (1H, ABdd, J=16.38, 6.85, 2.64 Hz); 2.58 (1H, ABdd, J=16.27, 6.43, 2.63 Hz); 2.04 (1H, t, J=2.60 Hz); 0.98 (9H, s); 0.91(12H, s); 0.18 (15H, s); 0.16 (3H, s); 0.15 (3H, s) ppm for 12: 7.14 (1H, d, J=8.51 Hz); 6.63 (1H, dd, J=8.37, 2.61 Hz); 6.55 (1H, d, J=2,55 Hz); 4.80 (1H, dd, J=8.16, 6.76 Hz); 4.41 (1H, m); 2.58 (1H, ABdd, J=16.47, 6.63, 3.20 Hz); 2.50 (1H, broad dd, 1=16.27, 8.24 Hz); 0.97 (9H, s); 0.92 (3H, s); 0.90 (9H, s); 0.31 (9H, s); 0.19 (6H, s); 0.15 (3H, s); 0.10 (3H, s) ppm for 13: 7.13 (1H, d, J=8.14 Hz); 6.62 (1H, dd, J=8.44, 2.65 Hz); 6.55 (1H, d, J=2.61 Hz), 4.85 (1H, dd, J=8.59, 6.76 Hz); 4.53 (1H, m); 2.63 (1H, ABdd, J=16.31, 6.76, 1.26 Hz); 2.47 (1H, ABdd, J=16.08, 8.60, 3.32 Hz); 0.98 (9H, s); 0.90 (9H, s); 0.87(3H, s); 0.23 (9H, s); 0.18 (6H, s); 0.14 (3H, s); 0.11 (3H, s)ppm for 14: 7.12 (1H, d, J=8.45 Hz); 6.62 (1H, dd, J=8.40, 2.52 Hz); 6.55 (1H, d, J=2.44 Hz); 4.91 (1H, t, J=6.41 Hz); 2.82 (1H, ABd, J=17.39, 6.32 Hz); 2.69 (1H, ABd, J=17.40, 6.54 Hz); 0.98 (9H, s); 0.92 (9H, s); 0.87(3H, s); 0.22 (9H, s); 0.19 (6H, s); 0.16 (3H, s); 0.13 (3H, s) ppm for 15: 7.30 (1H, d, J=8.64 Hz); 7.04 (1H, dd, J=8.67, 2.69 Hz); 7.00 (1H, broad s); 5.67 (1H, t, J=6,46 Hz); 3.19 (3H, s); 3.13 (3H, s); 0.94 (3H, s)ppm for 17: 7.84 (1H, dd, J=7.70, 1.10 Hz); 7.64 (1H, dd, J=8.05, 1.31 Hz); 7.61 (1H, dt, J=6.85, 1.32 Hz); 7.43 (1H, dt, J=7.82, 1.39 Hz); 7.20 (1H, d, J=8.63 Hz); 6.99 (1H, dd, J=8.60, 2.40 Hz); 6.94 (1H, d, J=2.44 Hz); 3.10 (3H, s); 1.18 (3H, s) ppm
30. 14. Takano, S.; Setoh, M.; Yamada, O.; Ogasawara, K. Synthesis 1993, 1253-1256.
31. 1H-NMR analysis of the O-methylmandelic acid derivatives obtained from (-)-5 and from (±)-5; see Raban, M.; Mislow, K. Top. Stereochem. 1967, 2, 199-230.
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33. (b). Trost, B.M.; Belletire, J.L.; Godleski, S.; McDougal, P.G.; Balkovec, J.M. J. Org. Chem. 1986, 51, 2370-2374.
34. 17. Schmidt, H.M.; Arens, J.F. Recueil 1967, 86, 1138-1142.
35. 1H-NMR showed this compound to be somewhat contaminated by the corresponding deiodinated derivative (less than 20%).
36. 19. Emde, H.; Domsch, D.; Feger, H.; Frick, U.; Götz, A.; Hergott, H.; Hofmann, K.; Kober, W.; Krägeloh, K.; Oesterle, T.; Steppan, W.; West, W.; Simchen, G. Synthesis 1982, 1-26.
37. 20. (a). Crevisy, C.; Beau, J.-M. Tetrahedron Lett. 1991, 32, 3171-3174;
38. (b). Maier, M.E.; Brandstetter, T. ibid. 1992, 33, 7511-7514;
39. (c). see also: Wender, P.A.; McKinney, J.A.; Mukai, C. J. Am. Chem. Soc. 1990, 112, 5369-5370.
40. 21. Dess, D.B.; Martin, J.C. J. Org. Chem. 1983, 48, 4155-4156.
41. 22. The stereochemistry of the two alcohols 12 and 13 rests on the comparison of experimental and calculated vicinal coupling constant values as indicated in ref. 5a.
42. 23. Newton, R.F.; Reynolds, D.P.; Finch, M.A.W.; Kelly, D.R.; Roberts, S.M. Tetrahedron Lett. 1979, 20, 3981-3982.
43. 24. Nicolaou, K.C.; Liu, A.; Zeng, Z.; McComb, S. J. Am. Chem. Soc. 1992, 114, 9279-9282.