Total synthesis of gambierol: Subunit coupling and completion

Chemistry - A European Journal

Volumn 12, Issue 6, 2006, Pages 1747-1753

  Johnson, Henry W B ^a   Majumder, Utpal ^a   Rainier, Jon D ^a  

^a UNIVERSITY OF UTAH   (United States)

Author keywords

Gambierol; Glycosides; Metathesis; Natural products; Total synthesis

Indexed keywords

GAMBIEROL; GLYCOSIDES; METATHESIS; NATURAL PRODUCTS;

ETHERS; SYNTHESIS (CHEMICAL);

ORGANIC COMPOUNDS;

CIGUATOXIN; DYES, REAGENTS, INDICATORS, MARKERS AND BUFFERS; ESTER; ETHER DERIVATIVE; GAMBIEROL; POLYCYCLIC HYDROCARBON;

ARTICLE; CATALYSIS; CYCLIZATION; SYNTHESIS;

CATALYSIS; CIGUATOXINS; CYCLIZATION; ESTERS; ETHERS, CYCLIC; INDICATORS AND REAGENTS; POLYCYCLIC COMPOUNDS;

EID: 32944481434     PISSN: 09476539     EISSN: 15213765     Source Type: Journal    
DOI: 10.1002/chem.200500994     Document Type: Article

References (48)

1. a) M. Satake, M. Murata, T. Yasumoto, J. Am. Chem. Soc. 1993, 115, 361;
2. b) A. Morohashi, M. Satake, T. Yasumoto, Tetrahedron Lett. 1998, 39, 97.
3. a) H. Fuwa, N. Kainuma, K. Tachibana, M. Sasaki, J. Am. Chem. Soc. 2002, 124, 14983;
4. b) I. Kadota, H. Takamura, K. Sata, A. Ohno, K. Matsuda, M. Satake, Y. Yamamoto, J. Am. Chem. Soc. 2003, 125, 11893.
5. In Yasumoto's original isolation, 1100 L of fermentation broth resulted in 1.2 mg of gambierol.
6. Some SAR work has already been carried out, see a) E. Ito, Suzuki-F. Toyota, K. Tashimori, H. Fuwa, K. Tachibana, M. Sataki, M. Sasaki, Toxicon 2003, 42, 733;
7. b) H. Fuwa, K. Kainuma, K. Tachibana, C. Tsukano, M. Satake, M. Sasaki, Chem. Eur. J. 2004, 10, 4894;
8. c) H. Fuwa, H. Kainuma, M. Satake, M. Sasaki, Bioorg. Med. Chem. Lett. 2003, 13, 2519.
9. a) O. Fujimura, G. C. Fu, R. H. Grubbs, J. Org. Chem. 1994, 59, 4029;
10. b) J. S. Clark, J. G. Kettle, Tetrahedron Lett. 1997, 38, 123;
11. c) M. H. D. Postema, J. Org. Chem. 1999, 64, 1770;
12. d) J. S. Clark, O. Hamelin, Angew. Chem. 2000, 112, 380;
13. Angew. Chem. Int. Ed. 2000, 39, 372;
14. e) A. K. Chatterjee, J. P. Morgan, M. Scholl, R. H. Grubbs, J. Am. Chem. Soc. 2000, 122, 3783;
15. f) J. D. Rainier, J. M. Cox, S. P. Allwein, Tetrahedron Lett. 2001, 42, 179.
16. a) K. C. Nicolaou, C. V. C. Prasad, C.-K. Hwang, M. E. Duggan, C. A. Veale, J. Am. Chem. Soc. 1989, 111, 5321;
17. b) K. C. Nicolaou, C. K. Hwang, D. A. Nugiel, J. Am. Chem. Soc. 1989, 111, 4136.
18. U. Majumder, J. M. Cox, H. W. B. Johnson, J. D. Rainier, Chem. Eur. J. 2006, 12, 1736.
19. For other examples of this reduction see: a) J. M. Cox, J. D. Rainier, Org. Lett. 2001, 3, 2919;
20. b) U Majumder, J. M. Cox, J. D. Rainier, Org. Lett. 2003, 5, 913;
21. c) K. Fujiwara, D. Awakura, M. Tsunashima, A. Nakamura, T. Honma, A. Murai, J. Org. Chem. 1999, 64, 2616;
22. ref. [7].
23. K. Tsushima, K. Araki, A. Murai, Chem. Lett. 1989, 1313.
24. K. C. Nicolaou, K. R. Reddy, G. Skokotas, F. Sato, X.-Y. Xiao, C.-K. Hwang, J. Am. Chem. Soc. 1993, 115, 3558.
25. 3SiH, see P. A. Evans, J. Cui, S. J. Gharpure, R. J. Hinkle, J. Am. Chem. Soc. 2003, 125, 11456.
26. 3SiH, TMSOTf see K. Suzuki, T. Nakata, Org. Lett. 2002, 4, 3943.
27. See Supporting Information for the generation of 15.
28. 3SiH.
29. Generated in an analogous fashion to 23, see Supporting Information.
30. I. Shiina, M. Kubota, R. Ibuka, J. Org. Chem. 2004, 69, 1822.
31. J. Inanaga, K. Hirata, H. Saeki, T. Katsuki, M. Yamaguchi, Bull. Chem. Soc. Jpn. 1979, 52, 1989.
32. If the reaction was allowed to proceed for prolonged periods of time we observed significant decomposition of the anhydride.
33. In substrates containing olefinic esters, we have found the steric environment about the ester to be important in determining the amount of acyclic versus cyclic enol ether product, see U. Majumder, J. D. Rainier, Tetrahedron Lett. 2005, 46, 7209.
34. Attempts to generate either the acyclic or cyclic enol ethers using other alkylidene reagents (Tebbe, Petasis, Takeda) were unsuccessful.
35. The Tebbe reagent has been used to carry out related cyclizations: a) J. R. Stille, R. H. Grubbs, J. Am. Chem. Soc. 1986, 108, 855;
36. b) J. R. Stille, B. D. Santarsiero, R. H. Grubbs, J. Org. Chem. 1990, 55, 843;
37. c) K. C. Nicolaou, M. H. D. Postema, C. F. Claiborne, J. Am. Chem. Soc. 1996, 118, 1565;
38. d) K. C. Nicolaou, M. H. D. Postema, E. W. Yue, A. Nadin, J. Am. Chem. Soc. 1996, 118, 10335.
39. For a related transformation that utilizes the Takeda protocol, see: H. Uehara, T. Oishi, M. Inoue, M. Shoji, Y. Nagumo, M. Kosaka, J.-Y. Le Brazidec, M. Hirama, Tetrahedron 2002, 58, 6493.
40. T. Okazoe, K. Takai, K. Oshima, K. Utimoto, J. Org. Chem. 1987, 52, 4410.
41. Following the generation of the terminal alkene, ethylene had to be purged from the reaction flask with nitrogen in order to induce cyclization.
42. S. P. Allwein, J. M. Cox, B. E. Howard, H. W. B. Johnson, J. D. Rainier, Tetrahedron 2002, 58, 1997.
43. DFT calculations on model bicyclic oxepenes predict the same sense of facial selectivity as that observed experimentally. A. Orendt, S. W. Roberts, J. D. Rainier, unpublished results.
44. I. Kadota, A. Ohno, Y. Matsukawa, Y. Yamamoto, Tetrahedron Lett. 1998, 39, 6373.
45. P. Michel, A. Rassat, Tetrahedron Lett. 1999, 40, 8579.
46. I. Kadota, H. Ueno, A. Ohno, Y. Yamamoto, Tetrahedron Lett. 2003, 44, 8645.
47. E. J. Corey, K. Y. Yi, Tetrahedron Lett. 1992, 33, 2289.
48. In comparison, Sasaki's synthesis involved 71 steps (longest linear sequence, 107 total steps) and 0.57% overall yield while Yamamoto's synthesis required 66 steps (longest linear sequence, 102 total steps) and 1.2% overall yield. Both syntheses involved 24 post-coupling steps.