Synthesis and antibacterial activity of (1'R, 5R, 6R)-2-tert-butyl-6-(1'-hydroxyethyl)penem-3-carboxylic acid

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 5, 1997, Pages 623-628

  Pfaendler, Hans Rudolf ^a   Medicus, Claus ^a  

^a UNIVERSITY OF MUNICH   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

2 TERT BUTYL 6 (1' HYDROXYETHYL) 1 OXAPENEM 3 CARBOXYLATE POTASSIUM; 2 TERT BUTYL 6 (1' HYDROXYETHYL)PENEM 3 CARBOXYLATE POTASSIUM; CEFTAZIDIME; CLAVULANIC ACID; PENEM DERIVATIVE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; CHIRALITY; DRUG STABILITY; DRUG SYNTHESIS; ENTEROBACTER CLOACAE; ESCHERICHIA COLI; GRAM POSITIVE BACTERIUM; IN VITRO STUDY; KLEBSIELLA; STAPHYLOCOCCUS EPIDERMIDIS; STEREOCHEMISTRY;

EID: 0031552164     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)00070-X     Document Type: Article

References (17)

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8. 3, J = 6.6 Hz), 3.82 (dd, 1H, 6-H, J = 5.9 Hz, J = 1.5 Hz), 4.21 (dq, 1H, 1′-H, J = 6.6 Hz, J = 5.9 Hz), 5.55 (d, 1H, 5-H, trans, J = 1.5 Hz).
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13. 13. Interestingly, 2-tert-butyl-6,6-dimethylpenemcarboxylic acid potassium salt was found to have a reduced hydrolysis half life as compared to 1.
14. 2,4 no activity against gram-negative bacteria was observed, with 2, presumably because of its lipophilic nature, arising from the tert-butyl group. A similar behavior can be observed with all lipophilic ß-lactam antibiotics including penicillins, cephalosporins and carbapenems.
15. 5 the unsubstituted compound 1 was less active than the corresponding 6-hydroxyethylpenem 2, especially against ß-lactamase producing bacteria.
16. 16 Pfaendler, H.R.; Weisner, F.; Metzger, K. Bioorg. Med. Chem. Lett. 1993, 3, 2211.
17. 17 The ß-lactamases were available by the Sigma Chemical Co. (P 4524 type IV and P 3553).