Antipodal forms of cephem derivatives via stereochemical manipulations of the cephalosporin nucleus

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Francesco De Angelis, Alessandra Di Tullio, Cristina Mozzetti and Rosario Nicoletti


Abstract

Two complementary strategies have been developed in order to convert a cephalosporin derivative, characterized by the ‘natural’ absolute configuration of the two stereogenic centers, into its enantiomer, as an optically pure compound.


References

  1. E. J. Ariens, Med. Res. Rev., 1986, 6, 451 CAS.
  2. S. C. Stinson, Chem. Eng. News, 1992, 70, 46; 1993, 71, 38.
  3. A. Vlietinck, E. Roets, P. Claes, G. Janssen and H. Vanderhaeghe, J. Chem. Soc., Perkin Trans. 1, 1973, 937 RSC; J. E. Baldwin, R. Y. Chan and J. D. Sutherland, Tetrahedron Lett., 1994, 35, 5519 CrossRef CAS; D. R. Wagle, C. Garai, M. G. Monteleone and A. K. Bose, Tetrahedron Lett., 1988, 29, 1649 CrossRef CAS; C. Somoza and O. A. Mascaretti, Tetrahedron, 1988, 44, 7007 CrossRef CAS.
  4. T. Fekner, J. E. Baldwin, R. M. Adlington and C. J. Schofield, Chem. Commun., 1996, 1989 RSC.
  5. S. Kukolja, J. Am. Chem. Soc., 1971, 93, 6267 CrossRef CAS.
  6. S. Kukolja, J. Am. Chem. Soc., 1971, 93, 6269 CrossRef CAS.
  7. J. E. Baldwin and D. P. Hesson, J. Chem. Soc., Chem. Commun., 1976, 667 RSC; R. G. Micetich, R. Singh, W. O. Merlo, D. M. Tetteh, C. C. Shaw and R. B. Morin, Heterocycles, 1984, 22, 2757 CAS.
  8. At difference with our case, it is well-known [R. D. G. Cooper and D. O. Spry, in Cephalosporins and Penicillins, Chemistry and Biology, ed. E. H. Flynn, Academic Press, New York and London, 1972, p. 209] that oxidation with MCPBA of N-phthalimido-cis-penam and cephem derivatives affords almost exclusively the (1R)-sulfoxide Search PubMed.
  9. C. F. Murphy and J. A. Webber, in Cephalosporins and Penicillins, Chemistry and Biology, ed. E. H. Flynn, Academic Press, New York and London, 1972, p. 137 Search PubMed.
  10. Spectral data in agreement with the reported structures were obtained for all compounds. In particular, the cis, and trans arrangements of the β-lactam protons, as well as the chirality at S-1 of the sulfoxide derivatives, were precisely indicated by 1H NMR spectroscopy: P. V. De Marco and R. Nagarajan, in Cephalosporins and Penicillins, Chemistry and Biology, ed. E. H. Flynn, Academic Press, New York and London, 1972, p. 330 and pp. 349–353: Selected data for 8: mp = 176–179 °C; [α]365+ 238, [α]D+ 1 (c0.2, EtOH); δH(200 MHz, CDCl3) 2.38 (s, 3H), 3.28 (AB system, J 14, 2H), 3.86 (s, 3H), 5.15 (d, J 4, 1H), 5.75 (d, J 4, 1H), 7.88 (m, 4H); νmax(Nujol)/cm–1 1787 (br, C[double bond, length as m-dash]O β-lactam), 1729 (br, C[double bond, length as m-dash]O ester and imide); m/z(EI) 358 [M+Search PubMed.
  11. S. Kukolja and S. R. Lammert, J. Am. Chem. Soc., 1975, 97, 5582 CrossRef CAS; T. Kamiya, M. Hashimoto, O. Nakaguchi and T. Oku, Tetrahedron, 1979, 35, 323 CrossRef CAS.
  12. The only epimer absent in the routes described is the enantiomer of sulfoxide 11, which can be obtained, together with 9, by direct oxidation of 3.
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