Synthesis of cephems bearing olefinic sulfoxide side chains as potential β-lactamase inhibitors

Bioorganic and Medicinal Chemistry Letters

Volumn 6, Issue 13, 1996, Pages 1613-1618

  Farina, Vittorio ^a,b   Hauck, Sheila I ^a   Firestone, Raymond A ^a  

^a BRISTOL MYERS SQUIBB   (United States)

^b BOEHRINGER INGELHEIM PHARMACEUTICALS INC   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA LACTAMASE INHIBITOR; CEPHEM DERIVATIVE; SULFOXIDE;

ANALYTIC METHOD; ANTIBIOTIC RESISTANCE; ARTICLE; DRUG MECHANISM; DRUG SYNTHESIS; ENZYME INHIBITION; ENZYME KINETICS; MINIMUM INHIBITORY CONCENTRATION; STRUCTURE ACTIVITY RELATION;

EID: 0030576301     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(96)00285-5     Document Type: Article

References (13)

1. 2. For a brief review on recent developments in the β-lactam field, see: Dürckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K. H. Angew. Chem. Int. Ed. Engl. 1985, 24, 180. For a review on β-lactamase-mediated resistance, see: Madeiros, A. A.; Jacoby, G. A. in :Beta-Lactam Antibiotics for Clinical Use; Queener, S. F.; Webber, J. A.; Queener, S. W. Eds; Marcel Dekker Inc: New York, 1986; pp 49-84.
2. 2. For a brief review on recent developments in the β-lactam field, see: Dürckheimer, W.; Blumbach, J.; Lattrell, R.; Scheunemann, K. H. Angew. Chem. Int. Ed. Engl. 1985, 24, 180. For a review on β-lactamase-mediated resistance, see: Madeiros, A. A.; Jacoby, G. A. in :Beta-Lactam Antibiotics for Clinical Use; Queener, S. F.; Webber, J. A.; Queener, S. W. Eds; Marcel Dekker Inc: New York, 1986; pp 49-84.
3. 3. Knowles, J. R. Acc. Chem. Res. 1985, 18, 97.
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5. 5. Johnston, M.; Raines, R.; Walsh, C.; Firestone, R. A. J. Am. Chem. Soc. 1980, 702, 4241.
6. 6. Broaddus, C. D. Acc. Chem. Res. 1968, 1, 231.
7. 7. Keck, G. E.; Byers, J. H.; Tafesh, A. M. J. Org. Chem. 1988, 53, 1127.
8. 8. We used a Pirkle covalent D-Phenyl Glycine Column, 250 x 4.6 mm, and a Perkin-Elmer instrument, consisting of a Series 4 pump, an ISS-100 injector and an LC-235 detector (set at 230 nm). The eluant was 98.5% hexane/1.5% isopropanol, and the retention times of the two enantiomers were ca. 24 and 26 min, respectively.
9. 9. Solladié, G. Synthesis 1981, 185.
10. 10. Farina, V.; Hauck, S. I. J. Org. Chem. 1991, 56, 4317.
11. 11. Farina, V.; Krishnan, B. J. Am. Chem. Soc. 1991, 113, 9585.
12. 12. Electron-deficient substituents attached to sulfinyl sulfur lead to rate enhancements in the [2,3] shift. See: Tang, R.; Mislow, K. J. Am. Chem. Soc. 1970, 92, 2100.
13. 13. Control experiments showed that all tested compounds are stable under the assay conditions for the duration of the experiments.