A novel approach to the synthesis of precursors of tricyclic β-lactam antibiotics

European Journal of Organic Chemistry

Volumn , Issue 11, 1999, Pages 3067-3072

  Annunziata, Rita ^a   Benaglia, Maurizio ^a   Cinquini, Mauro ^a   Cozzi, Franco ^a   Poletti, Laura ^a   Raimondi, Laura ^a   Perboni, Alcide ^b  

^a UNIVERSITY OF MILAN   (Italy)

^b GSK   (Italy)

Author keywords

Asymmetric synthesis; Enolate; Imine; Lactams; Thioester

Indexed keywords

AZETIDINONE DERIVATIVE; BETA LACTAM ANTIBIOTIC;

ANTIMICROBIAL ACTIVITY; ARTICLE; CATALYSIS; DERIVATIZATION; DRUG SYNTHESIS; PROTON NUCLEAR MAGNETIC RESONANCE; REACTION ANALYSIS; STEREOCHEMISTRY;

EID: 0032698286     PISSN: 1434193X     EISSN: None     Source Type: Journal    
DOI: 10.1002/(sici)1099-0690(199911)1999:11<3067::aid-ejoc3067>3.0.co;2-k     Document Type: Article

References (43)

1. Review: C. Ghiron, T. Rossi, The Chemistry of Trinems in Targets in Heterocydic Systems - Chemistry and Properties (Eds.: O. A. Attanasi, D. Spinelli), Societa' Chimica Italiana, Rome, vol. 1, pp. 161-186, 1997; and references therein.
2. Review: J. Ngo, J. Castañer, Drugs of the Future 1996, 21, 1238-1245; and references therein.
3. References 1 and 2 list all the reported syntheses of compound 1. For more recent reports see: [3a] T. Murayama. S. Mitsuhashi, T. Miura, European Patent Application 97400458-2, 1998.
4. [3b] Y. Iso, Y. Nishitani, Heterocycles 1998, 48, 2287-2308.
5. See also: [3c] S. Hanessian, B. Reddy, Tetrahedron 1999, 55, 3427-3443.
6. Almost thirty different syntheses of 4 have been reported. For a review see: [4a] A. H. Berks, Tetrahedron 1996, 52, 331-375. For a synthesis based on the use of thioester 5 see:
7. [4b] F. Cozzi, R. Annunziata, M. Cinquini, L. Poletti, A. Perboni, B. Tamburini, Chirality, 1998, 10, 91-94.
8. These precursors can be achiral, racemic or enantiomerically pure. For examples see: [5a] T. Rossi, S. Biondi, S. Contini, R. J. Thomas, C. Marchioro, J. Am. Chem. Soc. 1995, 117, 9604-9605.
9. [5b] S. Hanessian, M. J. Rozema, J. Am. Chem. Soc. 1996, 118, 9884-9491.
10. [5c] T. Rossi, C. Marchioro, A. Paio, R. J. Thomas, P. Zarantonello, J. Org. Chem. 1997, 62, 1653-1661.
11. [6a] M. Panunzio, R. Camerini, R. Pachera, D. Donati, C. Marchioro, A. Perboni, Tetrahedron: Asymmetry 1996, 7, 2929-2938.
12. [6b] M. Panunzio, R. Camerini, A. Mazzoni, D. Donati, C. Marchioro, R. Pachera, Tetrahedron: Asymmetry 1997, 8, 15-18.
13. P. M. Jackson, S. M. Roberts, S. Davalli, D. Donati, C. Marchioro, A. Perboni, S. Provera, T. Rossi, J. Chem. Soc., Perkin Trans. 1 1996, 2029-2039.
14. [4b] and: [8a] R. Annunziata, M. Benaglia, A. Chiovato, M. Cinquini, F. Cozzi, Tetrahedron 1995, 51, 10025-10032.
15. [8b] V. Molteni, R. Annunziata, M. Cinquini, F. Cozzi, M. Benaglia, Tetrahedron Lett. 1998, 39, 1257-1260.
16. R. Annunziata, M. Cinquini, F. Cozzi, P. G. Cozzi, J. Org. Chem. 1992, 57, 4155-4162. (R)-5 was obtained in three simple steps from ethyl (A)-3-hydroxy butanoate in 83% yield. It is a white solid that can be stored at -20°C for at least six months without decomposition.
17. The allyl protecting group was selected among a few other tested groups (benzyl, trimethylsilyl, acetyl) because of its stability under the reaction conditions as well as its mild and selective removal.
18. For leading references to the generation of trichlorotitanium enolates by this procedure see: D. A. Evans, M. T. Bilodeau, T. C. Somers, J. Clardy, D. Cherry, Y Kato, J. Org. Chem. 1991, 56, 5750-5752; and references therein.
19. Best yields and stereoselectivities were obtained with 2 mol equiv. of 5 per mol equiv. of imine on maintaining the condensation temperature at -78°C for 5 h and then allowing the temperature to rise to room temp, overnight. Other stoichiometries and reaction conditions were tested with less success. For instance, when 1 mol equiv. of titanium enolate was employed, the yield dropped to 60%. When the condensation was started at -78°C and then immediately warmed to room temp, the yield of 7 remained unchanged (96%) but minor amounts (ca. 10%) of a 3,4-cis isomer were obtained.
20. When the deallylation reaction was attempted on the N-protected β-lactams these were quantitatively recovered.
21. G. I. Georg, J. Kant, H. S. Gill, J. Am. Chem. Soc. 1987, 109, 1129-1135.
22. D. M. Rudkevich, Z. Brzozka, M. Palys, H. Visser, W. Verboom, D. N. Reinhoudt, Angew. Chem. Int. Ed. Engl. 1994, 33, 467-468.
23. For a recent review on the stereoselective reduction of aromatic compounds see: T. J. Donohue, R. Garg, C. A. Stevenson, Tetrahedron: Asymmetry 1996, 7, 317-344.
24. [4a] For other references describing attack from the side of the H at C-4 on a trigonal carbon at C-4′ in β-lactams see: [17a] R. Annunziata, M. Benaglia, M. Cinquini, F. Cozzi, F. Ponzini, J. Org. Chem. 1993, 58, 4746-4748.
25. [17b] C. Palomo, A. Arrieta, F. P. Cossio, J. M. Aizpurua, A. Mielgo, N. Aurrekoetxea, Tetrahedron Lett. 1990, 31, 6429-6432.
26. While the Swern oxidation proceeded smoothly (typical yield 70 to 80%), the reduction was sluggish. Generally, recovery of the unchanged phenols was possible.
27. Solvents more polar than AcOEt are known to accelerate the hydrogenation; for examples see: J. H. Stocker, J. Org. Chem. 1962, 27, 2288-2289; J. C. Sircar, A. I. Meyers, J. Org. Chem. 1965, 30, 3206-3207. In our case however, their use resulted in extensive substrate decomposition.
28. Solvents more polar than AcOEt are known to accelerate the hydrogenation; for examples see: J. H. Stocker, J. Org. Chem. 1962, 27, 2288-2289; J. C. Sircar, A. I. Meyers, J. Org. Chem. 1965, 30, 3206-3207. In our case however, their use resulted in extensive substrate decomposition.
29. 4 reduction of the ketone generously provided by GlaxoWellcome.
30. 3/trioctylamine: [21a] F. Fache, S. Lehuede, M. Lemaire, Tetrahedron Lett. 1995, 36, 885-888;
31. 3)]: [21b] M. A. Bennet, T.-N. Huang, T. W. Turney, J. Chem. Soc., Chem. Commun. 1979, 312-313 reported inferior results in terms of chemical yield. Birch-type reductions led to N-C4 bond cleavage.
32. The Macromodel/Batchmin package was used: [22a] F. Mohamadi, N. G. J. Richards, W. C. Guida, R. Liskamp, M. Lipton, C. Caufield, G. Chang, T Hendrickson, W. C. Still, J. Comput. Chem. 1990, 11, 440-467; two thousand steps of Pseudo-Systematic Monte Carlo search were performed:
33. [22b] J. M. Goodman, W. C. Still, J. Comput. Chem. 1991, 12, 1110-1117;
34. four torsions (around the Me/O, C-3/C-3′, C-4/C-4′, and HO/C bonds were set as variables with the standard resolution and chirality check on the stereocenters to avoid epimerization; energy minimization with MM2 force field : [22c] U. Burkert, N. L. Allinger, Molecular Mechanics, ACS Monograph 177, American Chemical Society; Washington D.C., 1982; and Truncated Newton conjugated gradient:
35. [22d] J. W. Ponder, F. M. Richards, J. Comput. Chem. 1987, 8, 1016-1024) was subsequently performed, and duplicate conformers eliminated. Only unique conformations within 25 kJ/mol from the global minimum were saved. All conformations were sampled several times, thus ensuring the convergence of the search.
36. B. J. VanKeulen, R. M. Kellogg, O. Piepers, J. Chem. Soc., Chem. Commun. 1979, 285-286.
37. [5b]
38. J. Blum, I. Amer, K. P. C. Vollhardt, H. Schwartz, G. Höhne, J. Org. Chem. 1987, 52, 2804-2813. This catalyst was ineffective in the reduction of 11 and 14.
39. For a recent synthesis of a compound similar to 19 by aromatic ring reduction see: M. Anada, S. Hashimoto, Tetrahedron Lett. 1998, 39, 9063-9066.
40. R. DiFabio, T. Rossi, R. J. Thomas, Tetrahedron Lett. 1997, 38, 3587-3590.
41. S. F. Martin, T. H. Cheavens, Tetrahedron Lett. 1989, 30, 7017-7020.
42. S. F. Martin, P. J. Garrison, J. Org. Chem. 1981, 46, 3567-3568.
43. B. Bertani, R. DiFabio, C. Ghiron, A. Perboni, T. Rossi, R. J. Thomas, P. Zarantonello, Tetrahedron, 1997, 53, 15011-15028.