Total Synthesis of Epothilone A: The Olefin Metathesis Approach

Angewandte Chemie (International Edition in English)

Volumn 36, Issue 1-2, 1997, Pages 166-168

  Yang, Zhen ^a,b   He, Yun ^a,b   Vourloumis, Dionisios ^a,b   Vallberg, Hans ^a,b   Nicolaou, K C ^a,b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 0030850057     PISSN: 05700833     EISSN: None     Source Type: Journal    
DOI: 10.1002/anie.199701661     Document Type: Article

References (34)

1. a) G. Höfle. N, Bedorf, K. Gerth, H. Reichcnhach (GBF). DE-4138042. 1993 (Chem. Abstr. 1993, 120, 52841);
2. b) K. Gerth, N. Bedorf, G Höfle, H. Irschik. H. Reichenbach, J. Antibioi., 1996, 49, 560-563.
3. G. Höfle, N. Bedorf, H. Steinmetz. D. Schomburg, K. Gerth, H. Reichenbach. Angew. Chem. 1996, 108, 1671-1673; Angew chem. Int. Ed. Engl. 1996, 35, 1567-1569.
4. G. Höfle, N. Bedorf, H. Steinmetz. D. Schomburg, K. Gerth, H. Reichenbach. Angew. Chem. 1996, 108, 1671-1673; Angew chem. Int. Ed. Engl. 1996, 35, 1567-1569.
5. M. R. Grever, S. A. Schepartz, B. A. Chabner, Semin. Oncol. 1992, 19, 622- 638.
6. D. M. Bollug, P. A. McQuency, J. Zhu, O. Hensens, L. Koupal, J. Liesch, M. Goetz, E. Lazarides, C. M. Woods, Cancer Res. 1995, 55, 23:5-2333.
7. K. C. Nicolaou, W-M. Dai, R. K. Guy, Angew. Chem. 1994, 106, 38-67; Angew. Chem. Int. Ed. Engl. 1994, 33, 15-44.
8. K. C. Nicolaou, W-M. Dai, R. K. Guy, Angew. Chem. 1994, 106, 38-67; Angew. Chem. Int. Ed. Engl. 1994, 33, 15-44.
9. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
10. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
11. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
12. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
13. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
14. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
15. K. C. Nicolaou, V. He, O. Vourloumis, H. Vullberg, Z. Yang, Angew, chem. 1996, 108, 2554-2556; Angew. Chem. Int. Ed. Engl. 1996, 35, 2399-2401. For other studies in the epothilone field, see a) D. Meng, E. J. Sorenscn, P. Bertinato. S. J. Danisheftky, J. Org. Chem. 1996, 61, 7998-7999; b) P. Bertnuto, E. J. Sorenwn, D. Meng, S. J. Danisheftky, J. Org. Chem. 1996, 61, 8000-8001; c) D. Shinzer, A. Limberg, O. M. Böhm, Chem. Eur. J. 1996. 2, 1477-1482. For the first total synthesis of epothilone A. see A. Bafog, D. Meng, T. Kamenecka, P. Berlinato, D.-S. Su, E. J. Sorensen, S. J. Danishefsky, Angew. Chem,. 1996, 108. 2976-2978. Angew. Chem. Int. Ed. Engl. 1996. 35. 2801-2803.
16. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
17. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
18. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
19. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
20. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
21. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
22. For the development of olefin metathesis as a ring forming reaction, see a) W. J. Zuercher. M. Hashimoto, R, H. Grubbs. J. Am. Chem. Soc. 1996. 118. 6634-6640; b) P. Schwab, R. H. Grubbs, J. W. Ziller. J. Am. Chem. Soc. 1996, 118, 100-110; c) R. H. Grubbs, S, J. Miller. G. C. Fu, Ace. Chem. Res. 1995. 28. 446-452 and references therein. For some earlier pioneering studies on this reaction. see a) T. J. Katz, S. J. Lee, N. Acton. Tetrahedron Lett. 1976, 4247- 4250; b) T. J. Katz, N. Acton. Tetrahedron Lett. 1976, 4251-4254; c) T. J. Katz. J. McGinnis, C. Altus. J. Am. Chem. Soc. 1976, 98, 606-608; d) T. J. Katz, Advances in Organomet Chem. 1977, 16, 283-317.
23. Ketoaldehyde 11 was prepared from propionyl chloride according to a published procedure: T. Inukai, R. Yoshizaiva, J. Org. Chem. 1967, 32, 404- 407.
24. U. S. Rucherla, H. C. Brown, J. Org. Chem. 1991, 56, 401-404.
25. lHNMR) revealed greater than 97% enamiomeric purity for compounds 3 and 10.
26. M. W. Bredenkamp, C. W. Holzapfel, W. J. van Zyl. Synthetic Commun. 1990. 20, 2235-2249.
27. A. Fürstner, K. Langemann, J. Org. Chem. 1996, 61, 3942-3943.
28. In this reaction (unoptimized) the eight-membered lactone corresponding to 11 was also observed (10-15%).
29. P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew. Chem. 1995, 107, 2179-2181; Angew. Chem. Int. Ed. Engl. 1995, 34, 2039-2041.
30. P. Schwab, M. B. France, J. W. Ziller, R. H. Grubbs, Angew. Chem. 1995, 107, 2179-2181; Angew. Chem. Int. Ed. Engl. 1995, 34, 2039-2041.
31. 13 of 11.0 Hz for the Z-isomer (13) and 15.0 Hz for the E-isomer.
32. We thank Dr. G. Höfle for kindly providing us with a natural sample of epothilone A (1).
33. All new compounds exhibited satisfactory spectral and analytical and/or exact mass data.
34. K. C. Nicolaou, F. Surabia, S. Ninkovic, Z. Yang, Angew. Chem. 1997, in press.