Piperidine analogues of D-galactose as potent inhibitors of α-galactosidase: Synthesis by stannane-mediated hydroxymethylation of 5-azido-1,4-lactones. Structural relationships between D-galactosidase and L-rhamnosidase inhibitors

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John P. Shilvock, Robert J. Nash, Alison A. Watson, Ana L. Winters, Terry D. Butters, Raymond A. Dwek, David A. Winkler and George W. J. Fleet


Abstract

The syntheses of the polyhydroxylated piperidines deoxygalactonojirimycin 2, homogalactonojirimycins 7 and 9, and other 2,6-iminoheptitol derivatives, including an analogue of L-altropyranose, are reported. 5-Azidoaldono-1,4-lactones undergo chain extension to afford azido lactols by the addition of a hydroxymethyllithium species 18, generated by transmetallation of a protected stannylmethanol derivative 17. Hydrogenation results in azide reduction with subsequent intramolecular reductive amination to give piperidine ring systems. The deprotected iminogalactopyranose analogues are potent and selective α-galactosidase inhibitors. Observations on the structural features determining selectivity of inhibition of α-galactosidases over naringinase (L-rhamnosidase) are also reported.


References

  1. Selected references for deoxynojirimycin analogues as inhibitors of carbohydrate processing enzymes: (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; (d) B. Winchester and G. W. J. Fleet, Glycobiology, 1992, 2, 199 CrossRef CAS; (e) A. B. Hughes and A. J. Rudge, Nat. Prod. Rep., 1994, 11, 153 RSC.
  2. G. Legler and S. Pohl, Carbohydr. Res., 1986, 155, 119 CrossRef CAS.
  3. G. W. J. Fleet, A. N. Shaw, S. V. Evans and L. E. Fellows, J. Chem. Soc., Chem. Commun., 1985, 841 RSC.
  4. (a) S. V. Evans, L. E. Fellows, G. W. J. Fleet and T. K. M. Shing, Phytochemistry, 1985, 24, 1953 CrossRef CAS; (b) B. Winchester, C. Barker, S. Baines, G. S. Jacob, S. K. Namgoong and G. W. J. Fleet, Biochem. J., 1990, 265, 277 CAS; (c) I. Bruce, G. W. J. Fleet, I. Cenci di Bello and B. Winchester, Tetrahedron Lett., 1989, 30, 7257 CrossRef CAS; (d) Tetrahedron, 1992, 46, 10191 Search PubMed.
  5. (a) 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; (b) J. P. Shilvock, J. R. Wheatley, R. J. Nash, A. A. Watson, R. C. Griffiths, T. D. Butters, M. Müller, D. J. Watkin, D. A. Winkler and G. W. J. Fleet, preceding paper (9/04064A).
  6. (a) I. Henderson, K. Laslo and C.-H. Wong, Tetrahedron Lett., 1994, 35, 359 CrossRef CAS; (b) K. E. Holt, F. J. Leeper and S. Handa, J. Chem. Soc., Perkin Trans. 1, 1994, 231 RSC; (c) Y. Suhura and K. Achiwa, Chem. Pharm. Bull., 1995, 43, 414 CAS; (d) N. Asano, M. Nishida, H. Kizu, K. Matsui, A. A. Watson and R. J. Nash, J. Nat. Prod., 1997, 60, 98 CrossRef CAS; (e) 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.
  7. (a) F. M. Platt, G. R. Nieses, G. B. Karlsson, R. A. Dwek and T. D. Butters, J. Biol. Chem., 1994, 269, 27108 CAS; (b) G. R. Nieses, P. G. Woodman, T. D. Butters, R. L. Ornberg and F. M. Platt, Biol. Cell, 1997, 89, 6733; (c) F. M. Platt, G. Reinkensmeir, R. A. Dwek and T. D. Butters, J. Biol. Chem., 1997, 272, 19365 CrossRef CAS.
  8. F. M. Platt and T. D. Butters, Trends Glycosci. Glycotechnol., 1995, 7, 495 Search PubMed.
  9. F. M. Platt, G. R. Neises, G. Reinkensmeier, M. J. Townsend, V. H. Perry, R. L. Proia, B. Winchester, R. A. Dwek and T. D. Butters, Science, 1997, 276, 428 CrossRef CAS.
  10. T. Kolter, Angew. Chem., Int. Ed. Engl., 1997, 36, 1955 CAS.
  11. (a) G. W. J. Fleet, S. Petursson, A. L. Campbell, A. L. Mueller, J. R. Behling, K. A. Babiak, J. S. Ng and M. G. Scaros, J. Chem. Soc., Perkin Trans. 1, 1989, 665 RSC; (b) D. M. Andrews, M. I. Bird, M. M. Cunningham and P. Ward, Bioorg. Med. Chem. Lett., 1993, 3, 2533 CrossRef CAS; (c) G. W. J. Fleet, S. K. Namgoong, C. Barker, S. Baines, G. S. Jacob and B. Winchester, Tetrahedron Lett., 1989, 30, 4439 CrossRef CAS.
  12. W. C. Still, J. Am. Chem. Soc., 1978, 100, 1481 CrossRef CAS.
  13. (a) M. Shiozaki, J. Org. Chem., 1991, 56, 528 CrossRef CAS; (b) M. Bols and W. A. Szarek, J. Chem. Soc., Chem. Commun., 1992, 445 RSC; (c) M. Bols, H. Grubbe, T. M. Jaspersen and W. A. Szarek, Carbohydr. Res., 1994, 253, 195 CrossRef CAS; (d) O. R. Martin and O. M. Saavedra, Tetrahedron Lett., 1995, 36, 799 CrossRef CAS; (e) O. M. Saavedra and O. R. Martin, J. Org. Chem., 1996, 61, 6987 CrossRef.
  14. (a) C. R. Johnson and J. R. Medich, J. Org. Chem., 1988, 53, 4131 CrossRef CAS; (b) R. L. Danheiser, K. R. Romines, H. Koyama, S. K. Gee, C. R. Johnson and J. R. Medich, Org. Synth., 1992, 71, 133.
  15. J. P. Shilvock and G. W. J. Fleet, Synlett, 1998, 554 CAS.
  16. O. Valera and P. A. Zunsain, J. Org. Chem., 1993, 58, 7860 CrossRef.
  17. (a) H. Paulsen, Y. Hayauchi and V. Sinnwell, Chem. Ber., 1980, 113, 2601 CrossRef CAS; (b) S. Aoyagi, S. Fujimaki, N. Yamazaki and C. Kibayashi, J. Org. Chem., 1991, 56, 815 CrossRef CAS; (c) R. Furneaux, P. C. Tyler and L. A. Whitehouse, Tetrahedron Lett., 1993, 34, 3609 CrossRef CAS; (d) N. Chida, T. Tanikawa, T. Tobe and S. Ogawa, J. Chem. Soc., Chem. Commun., 1994, 1247 RSC; (e) C. R. Johnson, A. Golebiowski, H. Sundram, M. W. Miller and R. L. Dwaihy, Tetrahedron Lett., 1995, 36, 653 CrossRef CAS; (f) P. L. Barili, G. Berti, G. Catelani, F. DíAndrea, F. De Rensis and L. Puccioni, Tetrahedron, 1997, 53, 3407 CrossRef CAS.
  18. G. W. J. Fleet, N. G. Ramsden and D. R. Witty, Tetrahedron, 1989, 45, 319 CrossRef CAS.
  19. O. R. Martin, F. Xie and L. Liu, Tetrahedron Lett., 1995, 36, 4027 CrossRef CAS.
  20. S. K. Namgoong, D.Phil. Thesis, University of Oxford, 1989.
  21. 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.
  22. D. A. Winkler, J. P. Shilvock and G. W. J. Fleet, manuscript in preparation.
  23. G. S. Jacob and P. Scudder, Methods Enzymol., 1994, 230, 280 CAS.
  24. 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.
  25. A. A. Watson, R. J. Nash, M. R. Wormald, D. J. Harvey, S. Dealler, E. Lees, N. Asano, H. Kizu, A. Kato, R. C. Griffiths, A. J. Cairns and G. W. J. Fleet, Phytochemistry, 1997, 46, 255 CrossRef CAS.
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