An efficient total synthesis of optically active tetrodotoxin from levoglucosenone

Chemistry - An Asian Journal

Volumn 1, Issue 1-2, 2006, Pages 125-135

  Urabe, Daisuke ^a   Nishikawa, Toshio ^a,b   Isobe, Minoru ^a  

^a NAGOYA UNIVERSITY   (Japan)

^b JAPAN SCIENCE AND TECHNOLOGY AGENCY   (Japan)

Author keywords

Asymmetric synthesis; Guanidine; Natural products; Tetrodotoxin; Total synthesis

Indexed keywords

1,6 ANHYDRO 3,4 DIDEOXYHEX 3 ENOPYRAN 2 ULOSE; 1,6-ANHYDRO-3,4-DIDEOXYHEX-3-ENOPYRAN-2-ULOSE; DRUG DERIVATIVE; FUSED HETEROCYCLIC RINGS; GLUCOSE; TETRODOTOXIN;

ARTICLE; CHEMISTRY; STEREOISOMERISM; SYNTHESIS;

BICYCLO COMPOUNDS, HETEROCYCLIC; GLUCOSE; STEREOISOMERISM; TETRODOTOXIN;

EID: 33748644699     PISSN: 18614728     EISSN: 1861471X     Source Type: Journal    
DOI: 10.1002/asia.200600038     Document Type: Article

References (63)

1. "Tetrodotoxin, Saxitoxin, and the Molecular Biology of the Sodium Channel" (Eds.: C. Y. Kao, S. Lovinson), Ann. N. Y. Acad. Sci. 1986, 479, 1-355.
2. a) T. Goto, Y. Kishi, S. Takahashi, Y. Hirata, Tetrahedron 1965, 21, 2059-2088;
3. b) K. Tsuda, S. Ikuma, M. Kawamura, R. Tachikawa, K. Sakai, C. Tamura, O. Amakasu, Chem. Pharm. Bull. 1964, 12, 1357-1374;
4. c) R. B. Woodward, Pure Appl. Chem. 1964, 9, 49-74.
5. a) T. Narahashi, J. Toxicol. Toxin Reviews, 2001, 20, 67-84;
6. b) T. Narahashi, J. W. Moore, W. Scott, J. Gen. Physiol. 1964, 47, 965-974.
7. a) T. Yasumoto, D. Yasumura, M. Yotsu, T. Michishita, A. Endo, Y. Kotaki, Agric. Biol. Chem. 1986, 50, 793-795;
8. b) T. Noguchi, J. K. Jeon, O. Arakawa, H. Sugita, Y. Deguchi, Y. Shida, K. Hashimoto, J. Biochem. 1986, 99, 311-314.
9. a) Review: M. Yotsu-Yamashita, J. Toxicol. Toxin Review, 2001, 20, 51-66;
10. 5,6,11-trideoxytetrodotoxin (T): b) M. Yotsu-Yamashita, Y. Yamagishi, T. Yasumoto, Tetrahedron Lett. 1995, 36, 9329-9332;
11. 11-deoxytetrodotoxin (2): c) T. Yasumoto, M. Yotsu, M. Murata, J. Am. Chem. Soc. 1988, 110, 2344-2345;
12. chiriquitoxin (4): d) M. Yotsu, T. Yasumoto, Y. H. Kim, H. Naoki, C. Y. Kao, Tetrahedron Lett. 1990, 31, 3187-3190;
13. 5-deoxytetrodotoxin (5): e) M. Yotsu-Yamashita, B. Schimmele, T. Yasumoto, Biosci. Biotechnol. Biochem. 1999, 63, 961 -963.
14. K. Matsumura, Nature 1995, 378, 563-564.
15. a) Y. Kishi, M. Aratani, T. Fukuyama, F. Nakatsubo, T. Goto, S. Inoue, H. Tanino, S. Sugiura, H. Kakoi, J. Am. Chem. Soc. 1972, 94, 9217-9219;
16. b) Y. Kishi, T. Fukuyama, M. Aratani, F. Nakatsubo, T. Goto, S. Inoue, H. Tanino, S. Sugiura, H. Kakoi, J. Am. Chem. Soc. 1972, 94, 9219-9221.
17. For leading references from other groups, see : a) D. F. Taber, P. H. Storck, J. Org. Chem. 2003, 68, 7768-7771;
18. b) Y. Ohtani, T. Shinada, Y. Ohfune, Synlett 2003, 619-622;
19. c) T. Itoh, M. Watanabe, T. Fukuyama, Synlett 2002, 1323-1325;
20. d) B. Noya, M. D. Paredes, L. Ozores, R. Alanso, J. Org. Chem. 2000, 65, 5960-5968;
21. e) B. Fraser-Reid, C S. Burgey, R. Vollerthun, Pure Appl. Chem. 1998, 70, 285-288;
22. f) R.J. Nachman, M. Hönel, T. M. Williams, R. C. Halaska, H. S. Mosher, J. Org. Chem. 1986, 51, 4802-4806;
23. g) J. F. Keana, J. S. Bland, P. J. Boyle, M. Erion, R. Harrtling, J. R. Husman, R. B. Roman, J. Org. Chem. 1983, 48, 3621-3631;
24. h) J. Speslacis, PhD Thesis, Harvard University, Cambridge MA, 1975.
25. N. Ohyabu, T. Nishikawa, M. Isobe, J. Am. Chem. Soc. 2003, 125, 8798-8805.
26. A. Hinman, J. Du Bois, J. Am. Chem. Soc. 2003, 125, 11510.
27. The total synthesis of racemic tetrodotoxin was reported recently:K. Sato, S. Akai, N. Sugita, T. Ohsawa, T. Kogure, H. Shoji, J. Yoshimura, J. Org. Chem. 2005, 70, 7496-7504.
28. The total synthesis of 5,6,11-trideoxytetrodotoxin (7) was reported recently: T. Umezawa, T. Shinada, Y. Ohfune, 47th Symposium on Natural Products (abstracts), Tokushima, Japan, Oct. 7-9, 2005, pp. 77-82.
29. a) T. Nishikawa, M. Asai, N. Ohyabu, N. Yamamoto, M. Isobe, Angew. Chem. 1999, 111, 3268-3271;
30. Angew. Chem. Int. Ed. 1999, 38, 3081-3084;
31. b) M. Asai, T. Nishikawa, N. Ohyabu, N. Yamamoto, M. Isobe, Tetrahedron 2001, 57, 4543-4558.
32. T. Nishikawa, M. Asai, M. Isobe, J. Am. Chem. Soc. 2002, 124, 7847-7852.
33. a) T. Nishikawa, D. Urabe, K. Yoshida, T. Iwabuchi, M. Asai, M. Isobe, Org. Lett. 2002, 4, 2679-2682;
34. b) T. Nishikawa, D. Urabe, K. Yoshida, T. Iwabuchi, M. Asai, M. Isobe, Chem. Eur. J. 2004, 10, 452-462.
35. T. Nishikawa, M. Asai, N. Ohyabu, N. Yamamoto, Y. Fukuda, M. Isobe, Tetrahedron 2001, 57, 3875-3883.
36. M. Isobe, N. Yamamoto, T. Nishikawa, in Levoglucosenone and Levglucosans, Chemistry and Applications. (Ed.: Z. J. Witczak), ATL Press, Mount Prospect, 1994, pp. 99-118.
37. T. Nishikawa, D. Urabe, M. Isobe, Angew. Chem. 2004, 116, 4886-4889;
38. Angew. Chem. Int. Ed. 2004, 43, 4782-4785.
39. a) N. Yamamoto, M. Isobe, Chem. Lett. 1994, 2299-2302;
40. b) T. Nishikawa, N. Ohyabu, N. Yamamoto, M. Isobe, Tetrahedron 1999, 55, 4325-4340.
41. For the conditions of these silylations, see: C. H. Heathcock, S. D. Young, J. P. Hagen, R. Pilli, U. Badertscher, J. Org. Chem. 1985, 50, 2095-2105.
42. K. A. Parker, A. Dermatakis, J. Org. Chem. 1997, 62, 6692-6696.
43. J. L. Luche, G. J. Gamal, J. Am. Chem. Soc. 1979, 101, 5848-5849.
44. Allylic oxidation of the corresponding acetonide under the same conditions gave an α,α-unsaturated ketone.
45. a) M. Isobe, H. Iio, T. Kawai, T. Goto, Tetrahedron Lett. 1977, 18, 703-706;
46. b) H. Iio, M. Isobe, T. Kawai, T. Goto, Tetrahedron 1979, 35, 941-948.
47. The same reaction with lithium acetylide gave the same diastereo-mixture in a 2:1 ratio.
48. P. H. Carisen, T. Katsuki, V. Martin, K. B. Shrapless, J. Org. Chem. 1981, 46, 3936-3938.
49. a) P. A. Grieco, D. L. Flynn, R. E. Zelle, J. Am. Chem. Soc. 1984, 106, 6414-6417;
50. b) P. A. Jacobi, S. Murphree, F. Rupprecht, W. Zheng, J. Org. Chem. 1996, 61, 2413-2427.
51. In order to synthesize 9-epi-tetrodotoxin from 20b, we attempted oxidative cleavage of the terminal acetylene, prepared from 20b in the same manner as shown in Scheme 5. However, exposure of the acetylene to the same conditions for the two-step cleavage gave only a complex mixture of products.
52. a) T. Oishi, K. Ando, K. Inomiya, H. Sato, M. Iida, N. Chida, Org. Lett. 2002, 4, 151-154;
53. b) T. Oishi, K. Ando, K. Inomiya, H. Sato, M. Iida, N. Chida, Bull. Chem. Soc. Jpn., 2002, 75, 1927-1947.
54. 13CNMR spectrum in the range characteristic of acetal carbon atoms (see the Supporting Information).
55. We propose the following mechanism for the deacetylation at C9: TBAF-promoted desilylation of the TES groups, concomitant formation of the orthoester, migration of the acetate to hydroxy group at C10, and hydrolysis of the acetate under these conditions. The labile nature of a similar acetate group under mild basic conditions was observed in the transformation of compound 35 into 36.
56. 13CNMR spectroscopy of product 30 obtained from the next reaction.
57. The trichloroacetamide group of compound a prepared from hydrolysis of 29 was successfully deprotected under the reductive conditions. However, the resulting amine b did not undergo guanidinylation under the same conditions.
58. D. Urabe, K. Sugino, T. Nishikawa, M. Isobe, Tetrahedron Lett. 2004, 45, 9405-9407.
59. a) K. S. Kim, L. Qian, Tetrahedron Lett. 1993, 34, 7677-7680;
60. b) R. J. Bergeron, J. S. McManis, J. Org. Chem. 1987, 52, 1700-1703.
61. Xie, M.; Berges, D. A.; Robins, M. J. Org. Chem. 1996, 61, 5178-5179.
62. The configuration of the acetal carbon atom was assigned on the basis of the coupling constant between 4-H and 4a-H.
63. The same reaction was conducted at about 0°C to give a complex mixture of products.