(+)-Phorboxazole A synthetic studies. Identification of a series of highly cytotoxic C(45-46) analogues

Organic Letters

Volumn 7, Issue 20, 2005, Pages 4403-4406

  Smith III, Amos B ^a   Razler, Thomas M ^a   Pettit, George R ^b   Chapuis, Jean Charles ^b  

^a UNIVERSITY OF PENNSYLVANIA   (United States)

^b ARIZONA STATE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CARBON; FUSED HETEROCYCLIC RINGS; OXAZOLE DERIVATIVE; PHORBOXAZOLE A;

ARTICLE; CELL PROLIFERATION; CHEMICAL STRUCTURE; CHEMISTRY; DRUG EFFECT; DRUG SCREENING; HUMAN; STRUCTURE ACTIVITY RELATION; SYNTHESIS; TUMOR CELL LINE;

CARBON; CELL LINE, TUMOR; CELL PROLIFERATION; DRUG EVALUATION, PRECLINICAL; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; HUMANS; MOLECULAR STRUCTURE; OXAZOLES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 26444435675     PISSN: 15237060     EISSN: None     Source Type: Journal    
DOI: 10.1021/ol051585a     Document Type: Article

References (26)

1. (a) Searle, P. A.; Molinski, T. F. J. Am. Chem. Soc. 1995, 117, 8126.
2. (b) Searle, P. A.; Molinski, T. F.; Brzezinski, L. J.; Leahy, J. W. J. Am. Chem. Soc. 1996, 118, 9422.
3. (c) Molinski, T. F. Tetrahedron Lett. 1996, 37, 7879.
4. (a) Forsyth, C. J.; Ahmed, F.; Cink, R. D.; Lee, C. S. J. Am. Chem. Soc. 1998, 120, 5597.
5. (b) Smith, A. B., III; Verhoest, P. R.; Minbiole, K. P.; Schelhaas, M. J. Am. Chem. Soc. 2001, 123, 4834.
6. (c) Smith, A. B., III; Minbiole, K. P.; Verhoest, P. R.; Schelhaas, M. J. Am. Chem. Soc. 2001, 123, 10942.
7. (d) González, M. A.; Pattenden, G. Angew. Chem., Int. Ed. 2003, 42, 1255.
8. (e) Pattenden, G.; González, M. A.; Little, P. B.; Millan, D. S.; Plowright, A. T.; Tornos, J. A.; Ye, T. Org. Biomol. Chem. 2003, 1, 4173.
9. (f) Williams, D. R.; Kiryanov, A. A.; Emde, U.; Clark, M. P.; Berliner, M. A.; Reeves, J. T. Angew. Chem., Int. Ed. 2003, 42, 1258.
10. (g) Evans, D. A.; Cee, V. J.; Smith, T. E.; Fitch, D. M.; Cho, P. S. Angew. Chem., Int. Ed. 2000, 39, 2533.
11. (h) Evans, D. A.; Fitch, D. M. Angew. Chem., Int. Ed. 2000, 39, 2536.
12. (i) Evans, D. A.; Fitch, D. M.; Smith, T. E.; Cee, V. J. J. Am. Chem. Soc. 2000, 122, 10033.
13. Uckun, F. M.; Forsyth, C. J. Bioorg. Med. Chem. Lett. 2001, 11, 1181.
14. Hansen, T. M.; Engler, M. M.; Forsyth, C. J. Bioorg. Med. Chem. Lett. 2003, 13, 2127.
15. Smith, A. B., III; Razler, T. M.; Ciavarri, J. P.; Hirose, T.; Ishikawa, T. Org. Lett. 2005, preceding Letter.
16. Smith, A. B., III; Minbiole, K. P.; Freeze, S. Synlett 2001, 1739.
17. Smith, A. B., III; Walsh, S. P.; Frohn, M.; Duffey, M. O. Org. Lett. 2005, 7, 139.
18. Poppe, L.; Recseg, K.; Novák, L. Synth. Commun. 1995, 25, 3993.
19. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277.
20. Hodgson, D. M.; Boulton, L. T.; Maw, G. N. Tetrahedron 1995, 51, 3713.
21. Carreira, E. M.; Du Bois, J. J. Am. Chem. Soc. 1995, 117, 8106.
22. Leusink, A. J.; Budding, H. A.; Drenth, W. J. Organomet. Chem. 1968, 11, 541.
23. Madec, D.; Férézou, J.-P. Tetrahedron Lett. 1997, 38, 6661.
24. The E-C(2-3)-macrocycle (+)-23 is the minor product from the Still-Genari-modified Horner-Emmons olefination. Smith, A. B., III; Razler, T. M.; Ciavarri, J. P.; Hirose, T.; Ishikawa, T. Org. Lett. 2005, preceding Letter.
25. We note that as the degree of unsaturation at C(45-46) decreased from alkynyl > alkenyl > alkyl the corresponding yields of the Stille reactions increased. This observation may be due to the propensity of palladium to coordinate with more electron-rich functional groups. As the C(45-46) electron density decreases, more palladium would be available to participate in the Stille cross-coupling. Union of the Z-C(2-3)-macrocycle (+)-13 with the C(45-46)-E-chloroalkene (-)-12 side chain proceeded with the highest yield and may reflect the electron-withdrawing capability of chlorine.
26. Global deprotection of central tetrahydropyran analogue (+)-30 required room temperature TBAF treatment for 2 h to effect BPS removal followed by hydrolysis with 6% HCl.