Studies toward a synthesis of epothilone A: Stereocontrolled assembly of the acyl region and models for macrocyclization

Journal of Organic Chemistry

Volumn 61, Issue 23, 1996, Pages 8000-8001

  Bertinato, Peter ^a   Sorensen, Erik J ^a   Meng, Dongfang ^a   Danishefsky, Samuel J ^a  

^a MEMORIAL SLOAN KETTERING CANCER CENTER   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CYTOTOXIC AGENT; EPOTHILONE A;

ARTICLE; CHIRALITY; DRUG SYNTHESIS; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0029849814     PISSN: 00223263     EISSN: None     Source Type: Journal    
DOI: 10.1021/jo961674o     Document Type: Article

References (23)

1. Meng, D.; Sorensen, E. J.; Bertinato, P.; Danishefsky, S. J. J. Org. Chem. 1996, 61, 7998-7999.
2. Danishefsky, S. J. Aldrichim. Acta 1986, 19, 59.
3. Danishefsky, S. J.; Yan, C.-F.; Singh, R. K. Gammill, R. B.; McCurry, P. M., Jr.; Fritsch, N.; Clardy, J. J. Am. Chem. Soc. 1979, 101, 7001.
4. (a) Danishefsky, S. J.; Pearson, W. H.; Harvey, D. F.; Maring, C. J.; Springer, J. P. J. Am. Chem. Soc. 1985, 107, 1256.
5. (b) Danishefsky, S. J.; Myles, D. C.; Harvey, D. P. J. Am. Chem. Soc. 1987, 109, 862.
6. Danishefsky, S. J. Chemtracts Org. Chem. 1989, 2, 273.
7. (a) Winstein, S.; Sonnenberg. J. J. Am. Chem. Soc, 1961, 83, 3235.
8. (b) Dauben, W. G.; Berezin, G. H. J. Am. Chem. Soc. 1963, 85, 468.
9. (c) Furukawa, J.; Kawabata, N.; Nishimura, J. Tetrahedron 1968, 24, 53.
10. For selected examples, see: (d) Boeckman, R. K., Jr.; Charette, A. B.; Asberom, T.; Johnston, B. H. J. Am. Chem. Soc. 1991, 113, 5337. (e) Hoberg, J. O.; Bozell, J. J. Tetrahedron Lett. 1995, 36, 6831.
11. For selected examples, see: (d) Boeckman, R. K., Jr.; Charette, A. B.; Asberom, T.; Johnston, B. H. J. Am. Chem. Soc. 1991, 113, 5337. (e) Hoberg, J. O.; Bozell, J. J. Tetrahedron Lett. 1995, 36, 6831.
12. Wenkert, E.; Mueller, R. A.; Reardon, E. J., Jr.; Sathe, S. S.; Scharf, D. J.; Tosi, G. J. Am. Chem. Soc. 1970, 92, 7428.
13. For example, exposure of 10 to acidic methanol gave rise to an epimeric mixture of seven- membered mixed acetals, presumably through the addition of methanol to oxocarbenium ion 11. This most interesting transformation is under active study in our laboratory.
14. For interesting Hg(II)-induced solvolyses of cyclopropanes that are conceptually similar to the conversion of 10 to 12, see: (a) Collum, D. B.; Still, W. C.; Mohamadi, F. J. Am. Chem. Soc. 1986, 108, 2094. (b) Collum, D. B.; Mohamadi, F.; Hallock, J. S. J. Am. Chem. Soc. 1983, 105, 6882. Following this precedent, we did, in fact, accomplish a Hg-(II)-induced solvolysis of cyclopropane 10, although this transformation proved to be less efficient than the reaction shown in Scheme 3.
15. For interesting Hg(II)-induced solvolyses of cyclopropanes that are conceptually similar to the conversion of 10 to 12, see: (a) Collum, D. B.; Still, W. C.; Mohamadi, F. J. Am. Chem. Soc. 1986, 108, 2094. (b) Collum, D. B.; Mohamadi, F.; Hallock, J. S. J. Am. Chem. Soc. 1983, 105, 6882. Following this precedent, we did, in fact, accomplish a Hg-(II)-induced solvolysis of cyclopropane 10, although this transformation proved to be less efficient than the reaction shown in Scheme 3.
16. (a) Schrock, R. R.; Murdzek, J. S.; Bazan, G. C.; Robbins, J.; DiMare, M.; O'Regan, M. J. Am. Chem. Soc. 1990, 112, 3875.
17. (b) Schwab, P.; France, M. B.; Ziller, J. W.; Grubbs, R. H. Angew. Chem., Int. Ed. Engl. 1995, 34, 2039.
18. For reviews of ring-closing metathesis, see: (c) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1985, 28, 446. (d) Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833.
19. For reviews of ring-closing metathesis, see: (c) Grubbs, R. H.; Miller, S. J.; Fu, G. C. Acc. Chem. Res. 1985, 28, 446. (d) Schmalz, H.-G. Angew. Chem., Int. Ed. Engl. 1995, 34, 1833.
20. Houri, A. F.; Xu, Z.; Cogan, D. A.; Hoveyda, A. H. J. Am. Chem. Soc. 1995, 117, 2943.
21. For recent examples of ring-closing metathesis, see: (a) Martin, S. F.; Chen, H.-J.; Courtney, A. K.; Liao, Y.; Pätzel, M.; Ramser, M N.; Wagman, A. S. Tetrahedron 1986, 52, 7251. (b) Fürstner, A.; Langemann, K. J. Org. Chem. 1996, 61, 3942.
22. For recent examples of ring-closing metathesis, see: (a) Martin, S. F.; Chen, H.-J.; Courtney, A. K.; Liao, Y.; Pätzel, M.; Ramser, M N.; Wagman, A. S. Tetrahedron 1986, 52, 7251. (b) Fürstner, A.; Langemann, K. J. Org. Chem. 1996, 61, 3942.
23. Substrates containing the full complement of oxygenated functionality, including the trisubstituted olefin and thiazolyl moiety, were screened for ring-closing olefin metathesis. In an effort to favor ring closure through the rigidification of the carbon backbone, a seco structure possessing a cyclic isopropylidene ketal bridging a C3-C5 diol relationship was prepared and subjected to ring-closing metathesis. In one instance, we also screened a substrate containing functionality that would lead to the C12-C13 epoxide, but lacking this function, per se. In spite of these setbacks, efforts to fashion the macrolide of epothilone A through ring-closing metathesis are continuing A full account of these studies will be disclosed in due course.