Synthesis and antibacterial activity of 4- and 8-methoxy trinems

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 4, 1996, Pages 491-496

  Andreotti, Daniele ^a   Rossi, Tino ^a   Gaviraghi, Giovanni ^a   Donati, Daniele ^a   Marchioro, Carla ^a   Di Modugno, Enza ^a   Perboni, Alcide ^a  

^a GSK   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; IMIPENEM; PENEM DERIVATIVE;

ANTIBACTERIAL ACTIVITY; ARTICLE; DRUG STABILITY; DRUG SYNTHESIS; ENANTIOMER; ENTEROCOCCUS FAECALIS; ESCHERICHIA COLI; STAPHYLOCOCCUS AUREUS; STEREOCHEMISTRY;

EID: 0029916261     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/0960-894X(96)00056-X     Document Type: Article

References (18)

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2. P.J. Reider, R. Rayford and E.J.J. Grabowski Tetrahedron Lett. 23, 379, (1982): M. Alpegiani, A. Bedeschi J. Am. Chem. Soc. 107, 6398, (1985): M. Fuentes, I. Shinkai, T.N. Salzmann J. Am. Chem. Soc. 108, 4675, (1986):
3. P.J. Reider, R. Rayford and E.J.J. Grabowski Tetrahedron Lett. 23, 379, (1982): M. Alpegiani, A. Bedeschi J. Am. Chem. Soc. 107, 6398, (1985): M. Fuentes, I. Shinkai, T.N. Salzmann J. Am. Chem. Soc. 108, 4675, (1986):
4. P.J. Reider, R. Rayford and E.J.J. Grabowski Tetrahedron Lett. 23, 379, (1982): M. Alpegiani, A. Bedeschi J. Am. Chem. Soc. 107, 6398, (1985): M. Fuentes, I. Shinkai, T.N. Salzmann J. Am. Chem. Soc. 108, 4675, (1986):
5. A.Yoshida, T. Hayashi, N. Takeda, S. Oida and E. Ohki Chem. Pharm. Bull. 31, 768, (1983).
6. P.D. Jeffrey and S.W. McCombie J. Org. Chem. 47, 587, (1982).
7. D.A. Evans, Asymmetric Synthesis, Vol. 3, Chap. 1, p. 1, Editor J.D. Morrison, (1984), Academic Press; Stereodifferentiating addition reactions Part. B, Selective Enolate Formation: Caine, D., Carbon-Carbon bond formation, Vol. 1, p. 85, Editor R.L. Augustine, (1979) New York: J. d'Angelo, Tetrahedron 32, 2979, (1976): J.-M. Poirier, L. Hennequin and M. Fornari, Bull. Soc. Chim. France, 436, (1986)
8. D.A. Evans, Asymmetric Synthesis, Vol. 3, Chap. 1, p. 1, Editor J.D. Morrison, (1984), Academic Press; Stereodifferentiating addition reactions Part. B, Selective Enolate Formation: Caine, D., Carbon-Carbon bond formation, Vol. 1, p. 85, Editor R.L. Augustine, (1979) New York: J. d'Angelo, Tetrahedron 32, 2979, (1976): J.-M. Poirier, L. Hennequin and M. Fornari, Bull. Soc. Chim. France, 436, (1986)
9. D.A. Evans, Asymmetric Synthesis, Vol. 3, Chap. 1, p. 1, Editor J.D. Morrison, (1984), Academic Press; Stereodifferentiating addition reactions Part. B, Selective Enolate Formation: Caine, D., Carbon-Carbon bond formation, Vol. 1, p. 85, Editor R.L. Augustine, (1979) New York: J. d'Angelo, Tetrahedron 32, 2979, (1976): J.-M. Poirier, L. Hennequin and M. Fornari, Bull. Soc. Chim. France, 436, (1986)
10. D.A. Evans, Asymmetric Synthesis, Vol. 3, Chap. 1, p. 1, Editor J.D. Morrison, (1984), Academic Press; Stereodifferentiating addition reactions Part. B, Selective Enolate Formation: Caine, D., Carbon-Carbon bond formation, Vol. 1, p. 85, Editor R.L. Augustine, (1979) New York: J. d'Angelo, Tetrahedron 32, 2979, (1976): J.-M. Poirier, L. Hennequin and M. Fornari, Bull. Soc. Chim. France, 436, (1986)
11. A.A. Ponaras, Y. Meah Tetrahedron Lett. 27, 4953-6, (1986).
12. 1-NMR assignment of trinems 3a-d.
13. 2O, 400MHz): 4.1-4.0 (2H, m), 3.88 (1H, dd, J1= 3.0 Hz, J2= 9.3 Hz), 3.27 (1H, dd, J1= 3.0 Hz, J2= 6.0 Hz), 3.20 (3H, s). 2.70 (1H, m), 1.95 (1H, m), 1.79 (1H, m), 1.62 (1H, m), 1.34 (1H, m), 1.30-1.00 (2H, m), 1.11 (3H, d, J= 6.7 Hz).
14. 2O, 400MHz): 4.79 (1H, t, J= 3.0 Hz), 4.13 (1H, m), 4.09 (1H, dd, J1= 2.8 Hz, J2= 10.3 Hz), 3.33 (1H, dd, J1= 2.8 Hz, J2= 6.1 Hz), 3.14 (3H, s), 3.05 (1H, m), 1.91 (1H, m), 1.77 (1H, m), 1.64-1.40 (3H, m), 1.25 (1H,m), 1.16 (3H, d, J= 6.1 Hz).
15. 2O, 400MHz): 4.76 (1H, t, J= 3.2 Hz), 4.07 (1H, m), 3.60 (1H, dd, J1= 3.0 Hz, J2= 7.3 Hz), 3.26 (1H, dd, J1= 3.0 Hz, J2= 5.8 Hz), 3.14 (3H, s), 2.99 (1H, m), 2.00-1.80 (2H, m), 1.50-1.00 (4H, m), 1.13 (3H, d, J= 6.3 Hz).
16. 2O, 400MHz): 4.05 (1H.m), 4.07 (1H, m), 3.81 (1H, m), 3.64 (1H, dd, J1= 2.8 Hz, J2= 7.3 Hz), 3.27 (3H, dd, J1= 2.8 Hz , J2= 5.8 Hz), 3.23 (3H, s), 2.87 (1H, m), 2.02 (1H, m), 1.90 (1H, m), 1.71 (1H, m), 1.22 (1H, m), 1.20-1.00 (2H,m), 1.12 (3H, d, J= 6.4 Hz).
17. 2O). Moreover, all the compounds herein described were characterized by routine analysis, and their absolute stereochemistry has been established by NOE measurements. A more detailed description of the NMR studies and assignments of absolute configuration will be reported elsewhere. Mass Spectra data were consistent with the proposed structures.
18. A complete in vitro antibacterial evaluation for isomer 3b is reported in: E. Di Modugno, I. Erbetti, L. Ferrari, G. Galassi, S. M. Hammond, L. Xerri Antimicrobial Agents and Chemotherapy 2362, (1994).