Chiral and stereoselective total synthesis of (-)-mesembranol starting from D-glucose

Abstract

A chiral synthesis of the Sceletium alkaloid (-)-mesembranol 1 is described. The cyclohexane ring in 1 is prepared in an optically active form from D-glucose using Ferrier’s carbocyclisation, and the critical stereochemistry of the quaternary carbon in 1 is constructed stereoselectively via chirality transfer by way of Claisen rearrangement of the cyclohexenol derivative 14a. The perhydroindole skeleton in 1 is effectively generated by intramolecular aminomercuriation of the amino-olefin 18.

References

1. R. J. Ferrier, J. Chem. Soc., Perkin Trans. 1, 1979, 1455; R. Blattner, R. J. Ferrier and S. R. Hains, J. Chem. Soc., Perkin Trans. 1, 1985, 2413.
2. N. Chida, M. Ohtsuka, K. Nakazawa and S. Ogawa, J. Org. Chem., 1991, 56, 2976; D. H. R. Barton, S. Augy-Dorey, J. Camara, P. Dalko, J. M. Delaumeny, S. D. Gero, B. Quiclet-Sire and P. Stütz, Tetrahedron, 1990, 46, 215; R. J. Ferrier and A. E. Stütz, Carbohydr. Res., 1990, 200, 237; M. Miyamoto, M. L. Baker and M. D. Lewis, Tetrahedron Lett., 1992, 33, 3725; N. Sakairi, M. Hayashida, A. Amano and H. Kuzuhara, J. Chem. Soc., Perkin Trans. 1, 1990, 1301; S. Takahashi, H. Terayama and H. Kuzuhara, Tetrahedron Lett., 1991, 32, 5123; K. Sato, S. Sakuma, S. Muramatsu and M. Bokura, Chem. Lett., 1991, 1473; V. A. Estevez and G. D. Prestwich, J. Am. Chem. Soc., 1991, 113, 9885; S. L. Bender and R. J. Budhu, J. Am. Chem. Soc., 1991, 113, 9883.
3. I. Dyong, H.-W. Hagedorn and J. Thiem, Liebigs Ann. Chem., 1986, 551; M. J. Fisher, C. D. Myers, J. Joglar, S.-H. Chen and S. J. Danishefsky, J. Org. Chem., 1991, 56, 5826; F. Chrétien, S. I. Ahmed, A. Masion and Y. Chapleur, Tetrahedron, 1993, 49, 7463; N. Chida, M. Ohtsuka and S. Ogawa, J. Org. Chem., 1993, 58, 4441; M. S. Ermolenko, A. Olesker and G. Lukacs, Tetrahedron Lett., 1994, 35, 715; M. S. Ermolenko, G. Lukacs and P. Poiter, Tetrahedron Lett., 1995, 36, 2465; T. K. Park and S. J. Danishefsky, Tetrahedron Lett., 1995, 36, 195; N. Chida, M. Jitsuoka, Y. Yamamoto, M. Ohtsuka and S. Ogawa, Heterocycles, 1996, 43, 1385.
4. For reviews of Sceletium alkaloids, see P. W. Jeffs, in The Alkaloids, ed. R. Rodrigo, Academic Press, New York, 1981, vol. 19, p. 1; S. F. Martin, in Studies in Natural Products Chemistry, ed. Atta-ur-Rahman, Elsevier, Amsterdam, 1989, vol. 4, p. 3.
5. For the structure determination of (–)-mesembranol, see (a) P. W. Jeffs, R. L. Hawks and D. S. Farrier, J. Am. Chem. Soc., 1969, 91, 3831For syntheses of (±)-mesembranol, see (b) P. W. Jeffs, N. A. Cortese and J. Wolfram, J. Org. Chem., 1982, 47, 3881; (c) H. Ishibashi, T. S. So, T. Sato, K. Kuroda and M. Ikeda, J. Chem. Soc., Chem. Commun., 1989, 762; (d) H. Ishibashi, T. S. So, K. Okochi, T. Sato, N. Nakamura, H. Nakatani and M. Ikeda, J. Org. Chem., 1991, 56, 95.
6. Preliminary communication of this work, see N. Chida, K. Sugihara and S. Ogawa, J. Chem. Soc., Chem. Commun., 1994, 901.
7. G. J. Robertson and W. Whitehead, J. Chem. Soc., 1940, 319.
8. S. Hanessian and N. R. Plessas, J. Org. Chem., 1969, 34, 1035.
9. N. Chida, M. Ohtsuka, K. Ogura and S. Ogawa, Bull. Chem. Soc. Jpn., 1991, 64, 2118.
10. G. E. Keck and R. R. Webb, II, J. Org. Chem., 1982, 47, 1302.
11. L. A. Paquette, J. C. Philips and R. E. Wingard, Jr., J. Am. Chem. Soc., 1971, 93, 4516.
12. T. W. Greene and P. G. M. Wuts, Protective Groups in Organic Synthesis, 2nd edn., John Wiley & Sons, Inc., New York, 1991, p. 17.
13. D. L. Hughes, Org. React., 1993, 42, 335.
14. For utilisation of the Claisen rearrangement in the synthesis of the related alkaloids, see ref. 9; (a) S. Kano, T. Yokoyama, Y. Yuasa and S. Shibuya, Chem. Lett., 1982, 1915; (b) H. F. Strauss and A. Wiechers, Tetrahedron Lett., 1979, 4495; (c) H. Fujioka, H. Annoura, K. Murano, Y. Kita and Y. Tamura, Chem. Pharm. Bull., 1989, 37, 2047; (d) S. Bauermeister, I. D. Gouws, H. F. Strauss and E. M. M. Venter, J. Chem. Soc., Perkin Trans. 1, 1991, 561.
15. (a) R. E. Ireland, P. Wipf and J. D. Armstrong, III, J. Org. Chem., 1991, 56, 650; (b) M. Miyashita, T. Suzuki and A. Yoshikoshi, J. Am. Chem. Soc., 1989, 111, 3728.
16. Y. Saitoh, Y. Moriyama, H. Hirota, T. Takahashi and Q. Khuong-Huu, Bull. Chem. Soc. Jpn., 1981, 54, 488.