Synthesis of homorhamnojirimycins and related trihydroxypipecolic acid derivatives via divergent bicyclic amino lactone intermediates: Inhibition of naringinase (L-rhamnosidase) and dTDP-rhamnose biosynthesis

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John P. Shilvock, Joseph R. Wheatley, Robert J. Nash, Alison A. Watson, Rhodri C. Griffiths, Terry D. Butters, Mathias Müller, David J. Watkin, David A. Winkler and George W. J. Fleet


Abstract

A series of homorhamnojirimycins and related compounds are prepared from two epimeric [2.2.2] bicyclic amino lactones 6 and 7 via the 2-azidoheptono-1,5-lactone 8, itself derived from L-rhamnose. Aminolysis and deprotection of the bicyclic lactones provides an efficient route to trihydroxypipecolic acid amide analogues of 5-epi-L-rhamnopyranose 12a–d and L-rhamnopyranose 14a–d. Some of the L-rhamnopyranose analogues display inhibitory activity against naringinase (L-rhamnosidase) and dTDP-rhamnose biosynthesis and are potentially useful as tools for investigating cell wall biosynthesis of Mycobacterium tuberculosis, the causative agent of tuberculosis. The synthesis of other homoiminosugar analogues including epi-homorhamnojirimycin (HRJ) 3 is also reported. Methanolysis of the bicyclic lactone 7 possessing a configuration corresponding to α-L-rhamnopyranose under basic conditions affords both α- and β-methyl 2,6-iminoheptonates 16 and 17. Reduction and subsequent deprotection affords the 2,6-iminoheptitols, α-homorhamnojirimycin (α-HRJ) 1 and β-homorhamnojirimycin (β-HRJ) 2, potent inhibitors of L-rhamnosidase and α-galactosidase, respectively. The crystal-structure determination of the bicyclic lactone 7 is also reported.


References

  1. (a) N. Asano, K. Oseki, H. Kizu and K. Matsui, J. Med. Chem., 1994, 37, 3701 CrossRef CAS; (b) N. Asano, M. Nishida, A. Kato, H. Kizu, K. Matsui, Y. Shimada, T. Itoh, M. Baba, A. A. Watson, R. J. Nash, P. M. de Q. Lilley, D. J. Watkin and G. W. J. Fleet, J. Med. Chem., 1998, 41, 2565 CrossRef CAS; (c) R. J. Nash, A. A. Watson and N. Asano, in Alkaloids: Chemical and Biological Perspectives, ed. S. W. Pelletier, Elsevier Science Ltd, Oxford, 1996, Vol. 11, pp. 345–376 Search PubMed.
  2. (a) F. M. Platt, G. R. Nieses, R. A. Dwek and T. D. Butters, J. Biol. Chem., 1994, 269, 14155; (b) F. M. Platt, G. R. Nieses, G. B. Karlsson, R. A. Dwek and T. D. Butters, J. Biol. Chem., 1994, 269, 27108 CAS; (c) A. Karpas, G. W. J. Fleet, R. A. Dwek, S. Petursson, S. K. Namgoong, N. G. Ramsden, G. S. Jacob and T. W. Rademacher, Proc. Natl. Acad. Sci. USA, 1988, 85, 9229 CAS; (d) G. W. J. Fleet, A. Karpas, R. A. Dwek, L. E. Fellows, S. Petursson, S. K. Namgoong, N. G. Ramsden, P. W. Smith, J. C. Son, F. Wilson, D. R. Witty, G. S. Jacob and T. W. Rademacher, FEBS Lett., 1988, 237, 128 CrossRef CAS; (e) G. B. Karlsson, T. D. Butters, R. A. Dwek and F. M. Platt, J. Biol. Chem., 1993, 268, 570 CAS; (f) P. E. Goss, M. A. Baker, J. P. Carver and J. W. Dennis, Clin. Cancer Res., 1995, 1, 935 CAS.
  3. B. Winchester and G. W. J. Fleet, Glycobiology, 1992, 2, 199 CrossRef CAS.
  4. A. B. Hughes and A. J. Rudge, Nat. Prod. Rep., 1994, 11, 153 RSC.
  5. (a) P. S. Liu, J. Org. Chem., 1987, 52, 4717 CrossRef CAS; (b) G. C. Kite, L. E. Fellows, G. W. J. Fleet, P. S. Liu, A. M. Scofield and N. G. Smith, Tetrahedron Lett., 1988, 29, 6483 CrossRef CAS; (c) J. P. Shilvock and G. W. J. Fleet, Synlett, 1998, 554 CAS and references cited therein.
  6. (a) N. Asano, M. Nishida, H. Kizu, K. Matsui, A. A. Watson and R. J. Nash, J. Nat. Prod., 1997, 60, 98 CrossRef CAS; (b) Y. C. Zeng, Y. T. Pan, N. Asano, R. J. Nash and A. D. Elbein, Glycobiology, 1997, 7, 297 CAS; (c) H. Nojima, I. Kimura, F. J. Chen, Y. Sugihara, M. Haruno, A. Kato and N. Asano, J. Nat. Prod., 1998, 61, 397 CrossRef CAS; (d) N. Asano, A. Kato, M. Miyauchi, H. Kizu, Y. Kameda, A. A. Watson, R. J. Nash and G. W. J. Fleet, J. Nat. Prod., 1998, 61, 625 CrossRef CAS.
  7. A. J. Fairbanks, N. M. Carpenter, G. W. J. Fleet, N. G. Ramsden, I. Cenci di Bello, B. G. Winchester, S. S. Al-Daher and G. Nagahashi, Tetrahedron, 1992, 48, 3365 CrossRef CAS.
  8. P. Zhou, H. M. Salleh, P. C. Chan, G. Lajoie, J. F. Honek, P. Nambiar and O. P. Ward, Carbohydr. Res., 1993, 239, 155 CrossRef CAS.
  9. L. Provencher, D. H. Steensma and C.-H. Wong, Bioorg. Med. Chem., 1994, 2, 1179 CrossRef CAS.
  10. J. P. Shilvock, J. R. Wheatley, R. J. Nash, R. C. Griffiths, M. G. Jones, M. Müller, S. Crook, D. J. Watkin, C. Smith, G. S. Besra, P. J. Brennan and G. W. J. Fleet, Tetrahedron Lett., 1996, 37, 8569 CrossRef CAS.
  11. B. G. Davis, A. Hull, C. Smith, R. J. Nash, A. A. Watson, D. A. Winkler, R. C. Griffiths and G. W. J. Fleet, Tetrahedron: Asymmetry, 1998, 9, 2947 CrossRef CAS.
  12. (a) D. D. Long, S. M. Frederiksen, D. G. Marquess, A. L. Lane, D. J. Watkin, D. A. Winkler and G. W. J. Fleet, Tetrahedron Lett., 1998, 39, 6091 CrossRef CAS; (b) J. P. Shilvock, R. J. Nash, J. D. Lloyd, A. L. Winters, N. Asano and G. W. J. Fleet, Tetrahedron: Asymmetry, 1998, 9, 3505 CrossRef CAS.
  13. (a) R. E. Lee, P. J. Brennan and G. S. Besra, Current Topics in Microbiology and Immunology, ed. T. M. Shinnick, Springer-Verlag, Berlin-Heidelberg, 1996, p. 1 Search PubMed; (b) M. R. McNeil and P. J. Brennan, Res. Microbiol., 1991, 142, 451 CrossRef CAS.
  14. (a) J. A. Maddry, N. Banasal, L. E. Bermudez, R. N. Comber, I. M. Orme, W. J. Suling, L. N. Wilson and R. C. Chambers, Bioorg. Med. Chem. Lett., 1998, 8, 237 CrossRef CAS; (b) R. E. Lee, P. J. Brennan and G. S. Besra, Bioorg. Med. Chem. Lett., 1998, 8, 951 CrossRef CAS; (c) C. Bouix, P. Bisseret and J. Eustache, Tetrahedron Lett., 1998, 39, 825 CrossRef CAS.
  15. (a) J. R. Wheatley, A. R. Beacham, P. M. de Q. Lilley, D. J. Watkin and G. W. J. Fleet, Tetrahedron: Asymmetry, 1994, 5, 2523 CrossRef CAS; (b) J. C. Estevez, M. D. Smith, M. R. Wormald, G. S. Besra, P. J. Brennan, R. J. Nash and G. W. J. Fleet, Tetrahedron: Asymmetry, 1996, 7, 391 CrossRef CAS.
  16. (a) I. Bruce, G. W. J. Fleet, I. Cenci di Bello and B. Winchester, Tetrahedron Lett., 1989, 30, 7257 CrossRef CAS; (b) I. Bruce, G. W. J. Fleet, I. Cenci di Bello and B. Winchester, Tetrahedron, 1992, 48, 10191 CrossRef CAS.
  17. G. Legler and S. Pohl, Carbohydr. Res., 1986, 155, 119 CrossRef CAS.
  18. Y. Tsukioka, Y. Yamashita, T. Oho, Y. Nakano and T. Koga, J. Bacteriol., 1997, 179, 1126 CAS and references cited therein.
  19. International Tables for Crystallography, Vol. IV, Kluwer Academic Publishers, Dordrecht, 1992.
  20. D. J. Watkin, C. K. Prout, J. R. Carruthers and P. W. Betteridge, CRYSTALS Issue 10, Chemical Crystallography Laboratory, University of Oxford, 1996.
  21. A. A. Watson, R. J. Nash, M. R. Wormald, D. J. Harvey, S. Dealler, E. Lees, A. Asano, H. Kizu, A. Kato, R. C. Griffiths, A. Cairns and G. W. J. Fleet, Phytochemistry, 1997, 46, 255 CrossRef CAS.
  22. G. S. Jacob and P. Scudder, Methods Enzymol., 1994, 230, 280 CAS.
  23. Data for Biochemical Research, eds. R. M. C. Dawson, D. C. Elliott, W. H. Elliott and K. M. Jones, Clarendon Press, Oxford, 1986 Search PubMed.
  24. L. Glaser and S. Kornfeld, Methods Enzymol., 1966, 8, 302 CAS.
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