A novel total synthesis of (±)-aspidospermidine

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Owen Callaghan, Christopher Lampard, Alan R. Kennedy and John A. Murphy


Abstract

The tetrathiafulvalene-induced ‘radical–polar crossover’ reaction has been applied to the total synthesis of the pentacyclic Aspidosperma alkaloid aspidospermidine.


References

  1. Previous syntheses of aspidospermidine: (a) A. Camerman, N. Camerman, J. P. Kutney, E. Piers and J. Trotter, Tetrahedron Lett., 1965, 637 CrossRef CAS ; (b) J. Harley-Mason and M. Kaplan, J. Chem. Soc., Chem. Commun., 1967, 915 RSC ; (c) J.-Y. Laronze, J. Laronze-Fontaine, J. Lévy and J. LeMen, Tetrahedron Lett., 1974, 491 CrossRef ; (d) T. Gallagher, P. Magnus and J. C. Huffman, J. Am. Chem. Soc., 1983, 105, 4750 CrossRef CAS ; (e) Y. Ban, K. Yoshida, J. Goto, T. Oishi and E. Takeda, Tetrahedron, 1983, 39, 3657 CrossRef CAS ; (f) M. Node, H. Nagasawa and K. Fuji, J. Am. Chem. Soc., 1987, 109, 7901 CrossRef CAS ; (g) S. B. Mandal, V. S. Giri, M. S. Sabeena and S. C. Pakrashi, J. Org. Chem., 1988, 53, 4236 CrossRef CAS ; (h) P. Le Ménez, N. Kunesch, S. Liu and E. Wenkert, J. Org. Chem., 1991, 56, 2915 CrossRef CAS ; (i) E. Wenkert and S. Liu, J. Org. Chem., 1994, 59, 7677 CrossRef CAS ; (j) D. Desmaële and J. d'Angelo, J. Org. Chem., 1994, 59, 2292 CrossRef ; (k) P. Forns, A. Diaz and M. Rubiralta, J. Org. Chem., 1996, 61, 7882 CrossRef CAS ; (l) A. G. Schultz and L. Pettus, J. Org. Chem., 1997, 62, 6855 CrossRef CAS .
  2. For synthesis of N-benzylaspidospermidine, see: N. Benchekroun-Mounir, D. Dugat, J.-C. Gramain and H.-P. Husson, J. Org. Chem., 1993, 58, 6457 Search PubMed .
  3. For a tandem radical approach to the Aspidosperma skeleton, see P. J. Parsons, C. S. Penkert, M. C. Cramp, R. I. West, J. Warrington and M. C. Saraiva, Synlett, 1995, 507 Search PubMed .
  4. Syntheses of vinblastine: P. Potier, N. Langlois, Y. Langlois and F. Guéritte, J. Chem. Soc., Chem. Commun., 1975, 670 Search PubMed ; J. Am. Chem. Soc., 1976, 98, 7017 RSC ; J. P. Kutney, A. H. Ratcliffe, A. M. Treasurywalla and S. Wunderly, Heterocycles, 1975, 3, 639 RSC ; G. Schill, C. U. Priester, U. F. Windhoevel and H. Fritz, Tetrahedron, 1987, 43, 3765 Search PubMed ; J. Vucovic, A. E. Goodbody, J. P. Kutney and M. Misawa, Tetrahedron, 1988, 44, 325 CAS ; P. Magnus, A. Stamford and M. Ladlow, J. Am. Chem. Soc., 1990, 112, 8210 CrossRef CAS ; M. E. Kuehne, P. A. Matson and W. G. Bornmann, J. Org. Chem., 1991, 56, 513 CrossRef CAS ; R. J. Sundberg, J.-L. Bettiol, K. G. Gadamasetti, M. Marshalla and L. Kelsh, Bioorg. Med. Chem. Lett., 1994, 4, 1999 CrossRef CAS ; I. Tabakovic, E. Gunic and I. Juranic, J. Org. Chem., 1997, 62, 947 CrossRef CAS .
  5. S. Lobert, B. Vulevic and J. J. Correia, Biochemistry, 1996, 35, 6806 CrossRef CAS ; S. S. Rai and J. Wolff, J. Biol. Chem., 1996, 271, 14707 CrossRef CAS ; V. Prakash and S. N. Timasheff, Biochemistry, 1991, 30, 873 CrossRef CAS ; L. S. Borman, M. E. Kuehne, P. A. Matson, I. Marko and T. C. Zebovitz, J. Biol. Chem., 1988, 263, 6945 CAS ; A. R. Safa, E. Hamel and R. L. Felsted, Biochemistry, 1987, 26, 97 CrossRef CAS .
  6. P. Potier, Semin. Oncol., 1989, 16, 2 CAS .
  7. D. L. J. Clive, Y. Tao, A. Khodabocus, Y.-J. Wu, A. G. Angoh, S. M. Bennett, C. N. Boddy, L. Bordeleau, D. Kellner, G. Kleiner, D. S. Middleton, C. J. Nichols, S. R. Richardson and P. G. Vernon, J. Am. Chem. Soc., 1994, 116, 11275 CrossRef CAS .
  8. D. L. J. Clive, H. W. Manning and T. L. B. Boivin, J. Chem. Soc., Chem. Commun., 1990, 972 RSC .
  9. A. L. J. Beckwith and G. F. Meijs, J. Org. Chem., 1987, 52, 1922 CrossRef CAS ; A. N. Abeywickrema and A. L. J. Beckwith, J. Org. Chem., 1987, 52, 2568 CrossRef CAS .
  10. C. Lampard, J. A. Murphy and N. Lewis, J. Chem. Soc., Chem. Commun., 1993, 295 RSC ; R. J. Fletcher, C. Lampard, J. A. Murphy and N. Lewis, J. Chem. Soc., Perkin Trans. 1, 1995, 623 RSC .
  11. R. Fletcher, M. Kizil, C. Lampard, J. A. Murphy and S. J. Roome, J. Chem. Soc., Perkin Trans. 1, 1998, 2341 RSC .
  12. K. Narasaka, K. Soai and T. Mukaiyama, Chem Lett, 1974, 1223 CAS ; T. Yanami, M. Miyashita and A. Yoshikoshi, J. Org. Chem., 1980, 45, 607 CrossRef CAS .
  13. Semi-empirical molecular modelling studies were performed at the AM1 level using Spartan 4.1, produced by Wavefunction Inc., Irvine, CA92715 .
  14. (a) For related studies, see: A. Azzouzi, B. Perrin, M.-E. Sinibaldi, J.-C. Gramain and C. Lavaud, Tetrahedron Lett., 1993, 34, 5451 Search PubMed ; (b) A. Azzouzi, B. Perrin, M. E. Sinibaldi, D. Gardette, C. Lavaud, D. Vallée-Goyet, J.-C. Gramain and A. Kerbal, Bull. Soc. Chim. Fr., 1995, 132, 681 CAS .
  15. E. Piers and J. Renaud, J. Org. Chem., 1993, 58, 11 CrossRef CAS .
  16. M. E. Kuehne, T. Wang and P. J. Seaton, J. Org. Chem., 1996, 61, 6001 CrossRef CAS .
  17. O. Callaghan, C. Lampard, A. R. Kennedy and J. A. Murphy, Tetrahedron Lett., 1999, 40, 161 CrossRef CAS .
  18. Enantiomerically pure aspidospermidine should be accessible by this route using a single enantiomer of 2-allylcylohex-2-en-1-ol, the ultimate source of this chiral centre (rather than the racemic compound used here). This compound has been prepared (ref. 19) in >96% ee and Mitsunobu reactions on cyclohex-2-enols have been found to proceed with clean inversion (ref. 20) of stereochemistry .
  19. C. Y. Hong, N. Kado and L. E. Overman, J. Am. Chem. Soc., 1993, 115, 11028 CrossRef CAS .
  20. K. A. Parker and D. Fokas, J. Am. Chem. Soc., 1993, 114, 9688 ; J. Org. Chem., 1994, 59, 3933 Search PubMed .
  21. TeXsan, Version 1.6, Crystal Structure Analysis Package, Molecular Structure Corporation, The Woodlands, Texas 77381, 1992 .
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