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DOI: 10.1039/A604564B (Paper) Reference Section for: J. Chem. Soc., Perkin Trans. 1, 1997, 503-510

An unexpected Mitsunobu reaction. A direct route to the 2,5-diazabicyclo[2.2.1]heptan-3-one skeleton as a γ-lactam mimic of β-lactam antibiotics

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Peter S. Hadfield, Ron H. B. Galt, Yvonne Sawyer, Nicola J. Layland and Michael I. Page

Abstract

Treatment of anilides of N-protected (2S,4R)-4-hydroxyproline, e.g. 1, with thioacetic acid under Mitsunobu conditions gives, unexpectedly, 2,5-diazabicyclo[2.2.1]heptan-3-ones, e.g. 2, the products of intramolecular cyclisation. However, the less acidic N-benzylamides of these proline derivatives, e.g. 7, are not sufficiently acidic and the hydrazido anion generated in the Mitsunobu reaction displaces the activated hydroxy group in an intermolecular reaction to give 8. The bicyclic γ-lactams are potential analogues of the β-lactam antibiotics and suitable derivatives 9, 10, 11 and 12 are found to be competitive inhibitors of class A and C β-lactamases, with Ki as low as 70 µM.

References

  1. J. L. Strominger, Antibiotics (NY), 1967, 1, 706 Search PubMed; R. B. Woodward, in The Chemistry of Penicillin, ed. H. T. Clarke, J. R. Johnson and R. Robinson, Princeton University Press, Princeton, New Jersey, 1949, p. 443 Search PubMed.
  2. M. I. Page, in The Chemistry of β-Lactams, ed. M. I. Page, Blackie, Glasgow, 1992, pp. 79–100 Search PubMed; M. I. Page, Acc. Chem. Res., 1984, 17, 144 Search PubMed.
  3. N. C. Cohen, J. Med. Chem., 1983, 26, 259 CrossRef CAS; D. R. Boyd, C. Eigenbrot, J. M. Indelicato, M. M. Miller, C. E. Pasini and S. R. Woulfe, J. Med. Chem., 1987, 30, 528 CrossRef CAS.
  4. J. Marchand-Brynaert and L. Ghosez, in Recent Progress in the Chemical Synthesis of Antibiotics, ed. M. Ohno and G. Lukais, Springer-Verlag, Berlin, 1990, pp. 729–794 Search PubMed; J. E. Baldwin, G. P. Lynch and J. Pitlik, J. Antibiot., 1991, 44, 1 Search PubMed.
  5. L. N. Jungheim and R. J. Ternansky, in The Chemistry of β-Lactams, ed. M. I. Page, Blackie, Glasgow, 1992, pp. 306–324 Search PubMed.
  6. L. N. Jungheim, D. B. Boyd, J. M. Indelicato, C. E. Pasini, D. A. Preston and W. E. Alborn, Jr., J. Med. Chem., 1991, 34, 1732 CrossRef CAS.
  7. J. Marchand-Brynaert, Z. Bounkhala-Khrouz, J. C. Carretero, J. Davies, D. Ferroud, B. J. van Keulen, B. Serckx-Poncin and L. Ghosez, in Recent Advances in the Chemistry of β-Lactam Antibiotics, ed. P. H. Bentley and R. Southgate, Royal Society of Chemistry, London, 1989, pp. 157–170 Search PubMed.
  8. J. E. Baldwin, C. Lowe and C. J. Schofield, Tetrahedron Lett., 1990, 31, 2211 CrossRef CAS.
  9. J. Marchand-Brynaert, E. Amadei and L. Ghosez, Bull. Soc. Chim. Belg., 1994, 103, 213 CAS.
  10. O. Mitsunobu, Synthesis, 1981, 1 CrossRef CAS.
  11. E. Grochowski, B. D. Hilton, R. J. Kupper and C. J. Michejda, J. Am. Chem. Soc., 1982, 104, 6876 CrossRef CAS.
  12. Sumitomo Chemical Co. Ltd., Japan, EP 0 126 587/ 1984.
  13. D. J. Abraham, M. Mokotoff, L. Sheh and J. E. Simmons, J. Med. Chem., 1983, 26, 549 CrossRef CAS; R. H. Andreatta, V. Nair, A. V. Robertson and W. R. J. Simpson, Aust. J. Chem., 1967, 20, 1493 CAS.
  14. D. Seebach, Angew. Chem., Int. Ed. Engl., 1990, 29, 1320 CrossRef; T. A. Alston, D. J. T. Porter and H. J. Bright, Acc. Chem. Res., 1983, 16, 418 CrossRef CAS.
  15. J. Jones, in Amino Acid and Peptide Synthesis, ed. S. G. Davies, Oxford Chemistry Primers, Oxford, Science Publ., 1992, p. 31 Search PubMed.
  16. S. G. Waley, in The Chemistry of β-Lactams, ed. M. I. Page, Chapman and Hall, London, 1992, pp. 198–228 Search PubMed.
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