Vancomycin CD and DE macrocyclization and atropisomerism studies

Journal of Organic Chemistry

Volumn 64, Issue 1, 1999, Pages 70-80

  Boger, Dale L ^a   Castle, Steven L ^a   Miyazaki, Susumu ^a   Wu, Jason H ^a   Beresis, Richard T ^a   Loiseleur, Olivier ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AMIDE; VANCOMYCIN;

ANTIMICROBIAL ACTIVITY; ARTICLE; BACTERIAL INFECTION; BINDING AFFINITY; CARBOXY TERMINAL SEQUENCE; DIASTEREOISOMER; DRUG SYNTHESIS; ISOMERISM; PROTON NUCLEAR MAGNETIC RESONANCE; STEREOCHEMISTRY;

EID: 0033534565     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo980880o     Document Type: Article

References (49)

1. McCormick, M. H.; Stark, W. M.; Pittenger, G. E.; Pittenger, R. C.; McGuire, G. M. Antibiot. Annu. 1955-1956, 606.
2. Harris, C. M.; Kopecka, H.; Harris, T. M. J. Am. Chem. Soc. 1983, 105, 6915. Williamson, M. P.; Williams, D. H. J. Am. Chem. Soc. 1981, 103, 6580. Sheldrick, G. M.; Jones, P. G.; Kennard, O.; Williams, D. H.; Smith, G. A. Nature (London) 1978, 271, 223. Williams, D. H.; Kalman, J. R. J. Am. Chem. Soc. 1977, 99, 2768.
3. Harris, C. M.; Kopecka, H.; Harris, T. M. J. Am. Chem. Soc. 1983, 105, 6915. Williamson, M. P.; Williams, D. H. J. Am. Chem. Soc. 1981, 103, 6580. Sheldrick, G. M.; Jones, P. G.; Kennard, O.; Williams, D. H.; Smith, G. A. Nature (London) 1978, 271, 223. Williams, D. H.; Kalman, J. R. J. Am. Chem. Soc. 1977, 99, 2768.
4. Harris, C. M.; Kopecka, H.; Harris, T. M. J. Am. Chem. Soc. 1983, 105, 6915. Williamson, M. P.; Williams, D. H. J. Am. Chem. Soc. 1981, 103, 6580. Sheldrick, G. M.; Jones, P. G.; Kennard, O.; Williams, D. H.; Smith, G. A. Nature (London) 1978, 271, 223. Williams, D. H.; Kalman, J. R. J. Am. Chem. Soc. 1977, 99, 2768.
5. Harris, C. M.; Kopecka, H.; Harris, T. M. J. Am. Chem. Soc. 1983, 105, 6915. Williamson, M. P.; Williams, D. H. J. Am. Chem. Soc. 1981, 103, 6580. Sheldrick, G. M.; Jones, P. G.; Kennard, O.; Williams, D. H.; Smith, G. A. Nature (London) 1978, 271, 223. Williams, D. H.; Kalman, J. R. J. Am. Chem. Soc. 1977, 99, 2768.
6. Nagarajan, R. J. Antibiot. 1993, 46, 1181. Cooper, R. D. G.; Thompson, R. C. Annu. Rep. Med. Chem. 1996, 31, 131. Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69.
7. Nagarajan, R. J. Antibiot. 1993, 46, 1181. Cooper, R. D. G.; Thompson, R. C. Annu. Rep. Med. Chem. 1996, 31, 131. Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69.
8. Nagarajan, R. J. Antibiot. 1993, 46, 1181. Cooper, R. D. G.; Thompson, R. C. Annu. Rep. Med. Chem. 1996, 31, 131. Malabarba, A.; Nicas, T. I.; Thompson, R. C. Med. Res. Rev. 1997, 17, 69.
9. Weidemann, B.; Grimm, H. In Antibiotics in Laboratory Medicine; Lorian, V., Ed.; Williams and Wilkins: Baltimore, 1996; pp 900-1168.
10. Williams, D. H.; Searle, M. S.; Westwell, M. S.; Mackay, J. P.; Groves, P.; Beauregard, D. A. Chemtracts: Org. Chem. 1994, 7, 133.
11. Walsh, C. T.; Fisher, S. L.; Park, I.-S.; Prahalad, M.; Wu, Z. Chem. Biol. 1996, 3, 21.
12. Reviews: Rao, A. V. R.; Gurjar, M. K.; Reddy, K. L.; Rao, A. S. Chem. Rev. 1995, 95, 2135. Evans, D. A.; DeVries, K. M. In Glycopeptide Antibiotics; Nagarajan, R., Ed.; Marcel Dekker: New York, 1994; pp 63-104.
13. Reviews: Rao, A. V. R.; Gurjar, M. K.; Reddy, K. L.; Rao, A. S. Chem. Rev. 1995, 95, 2135. Evans, D. A.; DeVries, K. M. In Glycopeptide Antibiotics; Nagarajan, R., Ed.; Marcel Dekker: New York, 1994; pp 63-104.
14. For recent disclosures: (a) Evans, D. A.; Barrow, J. C.; Watson, P. S.; Ratz, A. M.; Dinsmore, C. J.; Evrard, D. A.; DeVries, K. M.; Ellman, J. A.; Rychnovsky, S. D.; Lacour, J. J. Am. Chem. Soc. 1997, 119, 3419.
15. (b) Konishi, H.; Okuno, T.; Nishiyama, S.; Yamamura, S.; Koyasu, K.; Terada, Y. Tetrahedron Lett. 1996, 37, 8791.
16. (c) Pearson, A. J.; Zhang, P.; Bignan, G. J. Org. Chem. 1997, 62, 4536.
17. (d) Rao, A. V. R.; Gurjar, M. K.; Lakshmipathi, P.; Reddy, M. M.; Nagarajan, M.; Pal, S.; Sarma, B. V. N. B. S.; Tripathy, N. K. Tetrahedron Lett. 1997, 38, 7433.
18. (e) Bois-Choussy, M.; Vergne, C.; Neuville, L.; Beugelmans, R.; Zhu, J. Tetrahedron Lett. 1997, 38, 5795.
19. (f) Nicolaou, K. C.; Boddy, C. N. C.; Natarajan, S.; Yue, T.-Y. Li, H.; Brase, S.; Ramanjulu, J. M. J. Am. Chem. Soc. 1997, 119, 3421.
20. Boger, D. L.; Beresis, R. T.; Loiseleur, O.; Wu, J. H.; Castle, S. L. Bioorg. Med. Chem. Lett. 1998, 8, 721.
21. Boger, D. L.; Loiseleur, O.; Castle, S. L.; Beresis, R. T.; Wu, J. H. Bioorg. Med. Chem. Lett. 1997, 7, 3199.
22. Boger, D. L.; Borzilleri, R. M.; Nukui, S.; Beresis, R. T. J. Org. Chem. 1997, 62, 4721. Boger, D. L.; Borzilleri, R. M.; Nukui, S. Bioorg. Med. Chem. Lett. 1995, 5, 3091.
23. Boger, D. L.; Borzilleri, R. M.; Nukui, S.; Beresis, R. T. J. Org. Chem. 1997, 62, 4721. Boger, D. L.; Borzilleri, R. M.; Nukui, S. Bioorg. Med. Chem. Lett. 1995, 5, 3091.
24. Boger, D. L.; Borzilleri, R. M.; Nukui, S. J. Org. Chem. 1996, 61, 3561.
25. Boger, D. L.; Nomoto, Y.; Teegarden, B. R. J. Org. Chem. 1993, 58, 1425.
26. For additional studies, see: Beugelmans, R.; Singh, G. P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535. Rao, A. V, R.; Reddy, K. L.; Rao, A. S. Tetrahedron Lett. 1994, 35, 8465. Rao, A. V. R.; Reddy, K. L.; Rao, A. S.; Vittal, T. V. S. K.; Reddy, M. M.; Pathi, P. L. Tetrahedron Lett. 1996, 37, 3023. Evans, D. A.; Watson, P. S. Tetrahedron Lett. 1996, 37, 3251.
27. For additional studies, see: Beugelmans, R.; Singh, G. P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535. Rao, A. V, R.; Reddy, K. L.; Rao, A. S. Tetrahedron Lett. 1994, 35, 8465. Rao, A. V. R.; Reddy, K. L.; Rao, A. S.; Vittal, T. V. S. K.; Reddy, M. M.; Pathi, P. L. Tetrahedron Lett. 1996, 37, 3023. Evans, D. A.; Watson, P. S. Tetrahedron Lett. 1996, 37, 3251.
28. For additional studies, see: Beugelmans, R.; Singh, G. P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535. Rao, A. V, R.; Reddy, K. L.; Rao, A. S. Tetrahedron Lett. 1994, 35, 8465. Rao, A. V. R.; Reddy, K. L.; Rao, A. S.; Vittal, T. V. S. K.; Reddy, M. M.; Pathi, P. L. Tetrahedron Lett. 1996, 37, 3023. Evans, D. A.; Watson, P. S. Tetrahedron Lett. 1996, 37, 3251.
29. For additional studies, see: Beugelmans, R.; Singh, G. P.; Bois-Choussy, M.; Chastanet, J.; Zhu, J. J. Org. Chem. 1994, 59, 5535. Rao, A. V, R.; Reddy, K. L.; Rao, A. S. Tetrahedron Lett. 1994, 35, 8465. Rao, A. V. R.; Reddy, K. L.; Rao, A. S.; Vittal, T. V. S. K.; Reddy, M. M.; Pathi, P. L. Tetrahedron Lett. 1996, 37, 3023. Evans, D. A.; Watson, P. S. Tetrahedron Lett. 1996, 37, 3251.
30. For examples of such epimerizations preceding or accompanying macrocyclization with biaryl ether formation: (a) Pearson, A. J.; Zhang, P.; Bignan, G. J. Org. Chem. 1997, 62, 4536.
31. (b) Boger, D. L.; Zhou, J. J. Org. Chem. 1996, 61, 3938. Boger, D. L.; Zhou, J.; Borzilleri, R. M.; Nukui, S. Bioorg. Med. Chem. Lett. 1996, 6, 1089.
32. (b) Boger, D. L.; Zhou, J. J. Org. Chem. 1996, 61, 3938. Boger, D. L.; Zhou, J.; Borzilleri, R. M.; Nukui, S. Bioorg. Med. Chem. Lett. 1996, 6, 1089.
33. (c) Boger, D. L.; Zhou, J.; Borzilleri, R. M.; Nukui, S.; Castle, S. L. J. Org. Chem. 1997, 62, 2054.
34. (d) For observations analogous to those described herein, see: Pearson, A. J.; Chelliah, M. V. J. Org. Chem. 1998, 63, 3087.
35. 3OH-EtOAc 1:1, 25 °C, 5 h, 98%.
36. Upon completion of this work, we have established that the predominant extent of C14 epimerization occurs upon hydrolysis of the precursor methyl ester rather than during the amide coupling reaction. This can be minimized by conducting the hydrolysis at 0 °C for a minimum reaction period.
37. In preceding reports, we believe we have reversed the M and P stereochemical representations which may be attributed to ambiguities in the assignment of the pilot atom and its orientation for assignment of M and P: Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, 1994; pp 1120-1122 versus Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl. 1966, 5, 385. For the present assignments, the pilot atoms selected are the C15 OR (CD) and C15 OR (DE) substituents, and the chiral plane (the C ring for CD, the E ring for DE) is viewed from the point of view of the pilot atom (i.e., the pilot atom is placed above the chiral plane).
38. In preceding reports, we believe we have reversed the M and P stereochemical representations which may be attributed to ambiguities in the assignment of the pilot atom and its orientation for assignment of M and P: Eliel, E. L.; Wilen, S. H. Stereochemistry of Organic Compounds; Wiley: New York, 1994; pp 1120-1122 versus Cahn, R. S.; Ingold, C.; Prelog, V. Angew. Chem., Int. Ed. Engl. 1966, 5, 385. For the present assignments, the pilot atoms selected are the C15 OR (CD) and C15 OR (DE) substituents, and the chiral plane (the C ring for CD, the E ring for DE) is viewed from the point of view of the pilot atom (i.e., the pilot atom is placed above the chiral plane).
39. 2CN (m, δ 4.52/2.78 and 4.52/2.70).
40. Tentative C8 stereochemical assignments for 16 and 21 are also the unnatural, epimerized 8S stereochemistry. A conformational search of both atropisomers of the C8 diastereomers of 16 (MacroModel BatthMin 6.0, OPLSA) established that the unnatural 8S diastereomers were substantially more stable (ΔE = >2.5 kcal/mol). For 21, this is analogous to observations made with 4 and further supported by its relative ease of atropisomerism, see Table 2. Product 14 has been tentatively assigned the natural 8R stereochemistry on the basis of a conformational search (MacroModel, BatchMin 6.0, OPLSA) conducted on both atropisomers of the C8 diastereomers in which the natural, nonepimerized 8R configuration was established to be more stable (ΔE = 1.1-2.7 kcal/mol).
41. 5 requires 694).
42. 4, HOAc, 25 °C, 13.5 h, 84%).
43. Brown, H. C.; Narasimhan, S. J. Org. Chem. 1982, 47, 1604.
44. Garcia Ruano, J. L.; Martin Castro, A. M.; Rodriguez J. H. J. Org. Chem. 1992, 57, 7235.
45. 14Br requires 907.0438).
46. The stereochemical integrity of the C14 center was independently established by preparation and cyclization of the C14 hydroxymethyl derivative corresponding to 50 and the correlation of the product atropisomers with 51. Details are provided in supporting information.
47. Boger, D. L.; Miyazaki, S.; Loiseleur, O.; Beresis, R. T.; Castle, S. L.; Wu, J. H.; Jin, Q. J. Am. Chem. Soc. 1998, 120, 8920.
48. 2O, 45 °C, 1.5 h, 64%) without competitive ester hydrolysis. Katritzky, A. R.; Pilarski, B.; Urogdi, L. Synthesis 1989, 949.
49. Details of the preparation of 59 and 60 may be found in the Supporting Information.