Novel transannular rearrangements of azalide iminoethers

Tetrahedron

Volumn 53, Issue 50, 1997, Pages 16923-16944

  Wilkening, Robert R ^a   Ratcliffe, Ronald W ^a   Doss, George A ^a   Mosley, Ralph T ^a   Ball, Richard G ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ERYTHROMYCIN DERIVATIVE; MACROLIDE;

ARTICLE; DRUG SYNTHESIS; IN VITRO STUDY; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; PRIORITY JOURNAL; REACTION ANALYSIS; STEREOCHEMISTRY; THERMODYNAMICS;

EID: 0030735195     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0040-4020(97)10172-7     Document Type: Article

References (51)

1. a) Kirst, H. A.; Wind, J. A.; Paschal, J. W. J. Org. Chem. 1987, 52, 4359.
2. b) Kibwage, I. O.; Busson, R.; Janssen, G.; Hoogsmartens, J.; Vanderhaeghe, H. J. Org. Chem. 1987, 52, 990.
3. c) Perun, T. J. Org. Chem., 1967, 32, 2324.
4. d) Kibwage, I. O.; Janssen, G.; Busson, R.; Hoogmartens, J.; Vanderhaeghe, H. J. Antibiotics 1987, 40, 1.
5. e) Auricchio, S.; Fronza, G.; Meille, S. V.; Mele, A.; Favara, D. J Org. Chem. 1991, 56, 2250.
6. f) Nagel, A.; Celmar, W. D.; Jefferson, M. T.; Vincent, L. A.; Whipple, E. B.; Schulte, G. J. Org. Chem. 1986, 57, 5397.
7. a) Kirst, H. A. Recent Progress in the Chemical Synthesis of Antibiotics; Springer-Verlag, 1990; pp. 39-63.
8. b) Watanabe, Y.; Adachi, T.; Asaka, T.; Kashimura, M.; Morimoto, S. Heterocycles 1990, 31, 2121.
9. c) Counter, F. T.; Ensiminger, P. W.; Preston, D. A.; Wu, C. E.; Greene, J. M.; Felty-Duckworth, A. M.; Paschal, J. W.; Kirst, H. A. Antimicrob. Agents Chemother. 1991, 35, 1116. Gasc, J. C.; D'Ambrieres, A. L.; Lutz, A.; Chantot, J. F. J. Antibiotics 1991, 44, 313.
10. c) Counter, F. T.; Ensiminger, P. W.; Preston, D. A.; Wu, C. E.; Greene, J. M.; Felty-Duckworth, A. M.; Paschal, J. W.; Kirst, H. A. Antimicrob. Agents Chemother. 1991, 35, 1116. Gasc, J. C.; D'Ambrieres, A. L.; Lutz, A.; Chantot, J. F. J. Antibiotics 1991, 44, 313.
11. a) Wilkening, R. R.; Ratcliffe, R. W.; Doss, G. A.; Bartizal, K. F.; Graham, A. C.; Herbert, C. M. Bioorg. Med. Chem. Lett. 1993, 3, 1287.
12. b) Djokic', S.; Kobrehel, G.; Lazarevski, G.; Loppotar, N.; Tamburasev, Z.; Kamenar, B; Nagl, A.; Vickovic', I. J Chem. Soc. Perkin Trans. 1 1986, 1881.
13. Similar treatment of anhydroerythromycin 2 with potassium carbonate in refluxing methanol provides a 1 : 6 ratio of 2 : 3, see ref. 1a.
14. For clarity, the erythromycin numbering system is retained in all rearrangement products.
15. The ethylene glycol serves the dual purpose of activating the borohydride reducing agent and simplifying the workup by eliminating the borate complexes.
16. Attempted thermal equilibration of iminoether 8 results in the elimination of water to give the corresponding 10,11-anhydro derivative. This compound also forms on treatment of 8 with acetic acid, see réf. 10.
17. It is not clear from molecular models whether compound 11 results from a stereospecific reduction of the imino group from the β-face or whether reduction occurs from the α-face followed by rapid equilibration to a thermodynamically preferred form.
18. 1H NMR data and an X-ray structure were presented. Yang, B. V.; Goldsmith, M.; Rizzi, J. P. Tetrahedron Lett. 1994, 35, 3025.
19. Jones, A. B.; Herbert, C. M. Bioorg. Med. Chem. Lett. 1993, 3, 1999.
20. It was not possible for us to determine whether the enamine intermediate occurred in the 6.9-iminoether 4 or the 9,11-iminoether 15, or both, as these compounds exist in a dynamic equilibrium.
21. a) Kobrehel, G.; Lazarevski, G.; Djokic, S.; Kolacny-Babic, L. J. Antibiotics 1992, 45, 527.
22. b) Djokic, S; Kobrehel, G.; Lazarevski, G. J. Antibiotics, 1987, 40, 1006.
23. A similar transformation was recently reported in which the addition product of hydroxylamine and the 6,9-iminoether 4, a seco iminoether in which the carbonyl of the gamma-lactone 25 is replaced by an oxime function, rearranged to the analogous amide upon isolation. Lazarevski, G.; Kobrehel, G.; Metelko, B.; Duddeck, H. J. Antibiotics 1996, 49 1066.
24. The 6,9-iminoether 5 was found to be inert to the aqueous acetic acid conditions which hydrolyzed the 6,9-iminoether 4 and the 9,11-iminoether 15.
25. Jones, A. B. J. Org. Chem. 1992, 57, 4361.
26. b) Jones, A. B.; Herbert, C. M. J. Antibiotics 1992, 45, 1785.
27. Bax, A.; Freeman, R. J. Magn. Reson. 1981, 44, 542.
28. a) Braunschweiler, L.; Ernst, R. R. J. Magn. Reson. 1983, 53, 521.
29. b) Davis, D. G.; Bax, A. J. Am. Chem. Soc. 1985, 107, 2820.
30. c) Bax, A.; Davis, D. G. J. Magn. Reson. 1985, 65, 355.
31. a) Mohebbi, A.; Shaka, A. J. Chem. Phys. Lett. 1991, 178, 374.
32. b) Kadkhodaie, M.; Rivas, O.; Tan, M.; Mohebbi, A.; Shaka, A. J. J. Magn. Reson. 1991, 91, 437.
33. Bax, A.; Subramanian, S. J. Magn. Reson. 1986, 67, 565.
34. Bax, A.; Summers, M. F. J. Am. Chem. Soc. 1986, 108, 2093.
35. Lerner, L.; Bax, A. J. Magn. Reson. 1986, 69, 375.
36. a) Maudsley, A. A.; Muller, L.; Ernst, R. R. J. Magn. Reson. 1977, 28, 463.
37. b) Freeman, R.; Morris, G. A. J. Chem. Soc. Chem. Commun. 1978, 684.
38. c) Bax, A.; Sarkar, S. K. J. Magn. Reson. 1978, 60, 170.
39. a) Krishnamurthy V. V.; Nunlist, R. J. Magn. Reson. 1988, 80, 280.
40. b) Krishnamurthy, V. V.; Casida, J. E. Magn. Reson. Chem. 1988, 26, 362.
41. c) Martin, G. E.; Zektzer, A. S. Magn. Reson. Chem 1988, 26, 631.
42. a) Jeener, J.; Meier, B. H.; Bachmann, P.; Ernst, R. R. J. Chem. Phys. 1979, 71, 4546.
43. b) Macura, S.; Ernst, R. R. Mol. Phys. 1980, 41, 95.
44. c) Macura, S.; Huang, Y.; Suter, D.; Ernst, R. R. J. Magn. Reson. 1981, 43, 259.
45. d) States, D. J.; Haberkorn, R. A.; Ruben, D. J. J. Magn. Reson. 1982, 48, 286.
46. Halgren, T. A. J. Comp. Chem. 1996, 17, 490-519.
47. Coupling constants were calculated using the modified Karplus equation described in a) Haasnoot, C. A. G.; de Leeuw, F. A. A. M.; Altona, C. Tetrahedron 1980, 26, 2783.
48. b) Ramachandran, G. N.; Chandrasekaran, R. Biopolymers 1971, 10, 935.
49. Ramachandran, G. N.; Chandrasekaran, R.; Kopple. K. D. ibid., 2113.
50. Sheldrick, G.M. Acta Crystallogr. 1990, A46, 467.
51. Structure Determination Package Version 3, Enraf-Nonius, Delft, 1985.