Studies on the reactivity of azetidin-2-ones in phosphate buffer

Abstract

¹H NMR (500 MHz) analyses reveal that in phosphate buffer, N-arylsulfonyl β-lactams such as ethyl N-( p-nitrophenylsulfonyl)-2-oxoazetidine-4- carboxylate and (4S)-ethyl 3-ethyl-N-( p-nitrophenylsulfonyl)-2- oxoazetidine-4-carboxylate undergo hydrolysis through (minimally) two mechanisms: via direct hydrolysis and via an unstable acyl phosphate intermediate. The acyl phosphate intermediates can be trapped using hydrazine.

References

1. For reviews see: The Chemistry of β-Lactams, ed. M. I. Page, Blackie, London, 1992.
2. H. Bundgaard and J. Hansen, Int. J. Pharm., 1981, 9, 273 and references therein.
3. E. Pawelczyk, M. Zajac and B. Knitter, Pol. J. Pharmacol. Pharm., 1981, 33, 241 (Chem. Abstr., 1995, 192 282z).
4. E. E. Roets, A. J. Vlietinck, G. A. Janssen and H. Vanderhaeghe, J. Chem. Soc., 1973, 484.
5. For details of the mechanistic studies carried out by Merck Research Laboratories see: R. A. Firestone, P. L. Barker, J. M. Pisano, B. M. Ashe and M. E. Dahlgren, Tetrahedron, 1990, 46, 2255; R. A. Firestone, P. L. Barker, J. M. Pisano, B. M. Ashe and M. E. Dahlgren, Tetrahedron, 1990, 46, 6585; W. B. Knight, R. Chabin and B. Green, Arch. Biochem. Biophys., 1992, 296, 704; W. K. Hagmann, S. K. Shah, C. P. Dorn, L. A. O'Grady, J. J. Hale, P. E. Finke, K. R. Thompson, K. A. Brause, B. M. Ashe, H. Weston, M. E. Dahlgren, A. L. Maycock, P. S. Dellea, K. M. Hand, D. G. Osinga, R. J. Bonney, P. Davies, D. S. Fletcher and J. B. Doherty, Bioorg. Med. Chem. Lett., 1991, 1, 545; W. B. Knight, K. M. Swiderek, T. Sakuma, J. Calaycay, J. E. Shively, T. D. Lee, T. R. Covey, B. Shushan, B. G. Green, R. Chabin, S. Shah, R. Mumford, T. A. Dickinson and P. R. Griffin, Biochemistry, 1993, 32, 2031.
6. N. J. Westwood, DPhil Thesis, University of Oxford, 1995.
7. D. E. Koshland, Jr., J. Am. Chem. Soc., 1952, 74, 2286.
8. D. J. Palling and W. P. Jencks, J. Am. Chem. Soc., 1984, 106, 4869.
9. D. D. Perrin and W. L. F. Amarego, Purification of Laboratory Chemicals, Pergamon, Oxford, 1988.
10. W. C. Still, M. Kahn and A. Mitra, J. Org. Chem., 1978, 43, 2923.
11. W. McCoull, N. J. Westwood, R. M. Adlington, J. E. Baldwin and C. J. Schofield, Synlett, 1997, in the press.
12. P. J. Reider and E. J. J. Grabowski, Tetrahedron Lett., 1982, 23, 2293; J. E. Baldwin, R. M. Adlington, D. W. Gollins and C. J. Schofield, Tetrahedron, 1990, 46, 4733; S. Hanessian, K. Sumi and B. Vanasse, Synlett, 1992, 33.