B-Lactam

Lacquer thinners Lacrimators Lacrisert Lac sulfur b-lactam... 

Cyclisation of (12) to a B-lactam (13) is an attractive reaction for those wanting to synthesise antibiotics. What other reaction(s) might compete with the cyclisation and why ... 

Note TC, tetracycline CA, chloramphenicol FQ, fluoroquinoline FRY, erythromycin NOV, novobiocin RIF, rifampin and 6-LAC, B-lactam. 

Ojima, 1., Habus, 1., Zhao, M. (1991) Efficient and Practical Asymmetric Synthesis ofthe Taxol C-13 Side Chain, N-Benzoyl-(2R,3S)-3-phenylisoserine, and its Analogues via Chiral 3-Hydroxy-4-aryl-b-lactams Through Chiral Ester Enolate-Imine Cyclocondensation. Journal of Organic Chemistry, 56, 1681-1683. 

B-Lactams.- The now standard intramolecular Wittig cyclization procedure has been used110,111 to prepare a number of... 

Rzasa, R. M., Shea, H. A., and Romo, D. (1998). Total synthesis of the novel, immunosuppressive agent (-)-Pateamine A from Mycale sp. Employing a b-lactam-based macrocyclization. J. Am. Chem. Soc. 120, 591—592. 

Waxman, D.J. Strominger, J. L. (1983). Penicillin-binding proteins and the mechanism of action of B-lactam antibiotics. Annu. Rev. Biochem. 52, 825-869. 

Although many B-lactam antibiotics have been described, a relatively small number are used in food-producing animals and these are the only ones of concern as residues. Microbiological test procedures are ordinarily very sensitive to B-lactam antibiotics (49). 

Table II. Chromatographic Methods for Detection of B-lactam Antibiotic Residues in Foods...

Penicillins form several major metabolites which are excreted in the urine (83,84). These metabolites are usually inactive microbio-logically and they would not be detected by the usual microbiological tests. There are no analytical methods for these metabolites in tissues and, therefore, little is known as to their occurrence and persistence in tissues. There are no methods available for identifying residues of some commonly used B-lactam antibiotics including carbenicillin and ticarcillin. For cephapirin and ampicillin, except for one HPLC method for ampicillin in milk (79) only TLC procedures (72-74,76) with detection by bioautography are reported. 

Although some European countries still accept the results of the four plate test as confirming the presence of antibiotic residues in samples ( ), other work indicates that FPT test is not necessarily reliable. The occurrence of natural microbial inhibitors in tissues has frequently been noted (4,9,49,82), It has also been frequently observed that the results obtained by microbial and physicochemical procedures sometimes differ considerably (9,10,45,82,86), Results obtained in our laboratory suggest that even inactivation by penicillinase may not be totally specific for B-lactam antibiotics (W), The specificity of immunoassay procedures depends on the specificity of the antibody used in the test (95), Specific antisera are not widely available at present. Physicochemical procedures are therefore essential for identification and confirmation of suspect residues detected by microbiological tests. 

An important molecular target of the B-lactam antibiotics is an enzyme that acts as a transpeptidase in the stepwise polymerization leading to a thickened, strong bacterial cell wall. Several amino acids are present in addition to the terminal -alanyl- -alanyl unit which the Strominger hypothesis suggests has the same overall shape and reactivity as... 

Puffr, R., Raab, M., Dolezel, B., Lactam-Based Polyamides. Puffr, R., Kubanek V., eds. (1991) 1, Chapter 6, CRC Press, Boca Raton, Florida, p. 187... 

Ketones, preparation from carboxylic acid, 66, 119 B-Lactams, 65, 140... 

Core structures of four B-lactam antibiotic families. The ring marked in each structure is the -lactam ring. The penicillins are susceptible to bacterial metabolism and inactivation by amidases and lactamases at the points shown. Note that the carbapenems have a different stereochemical configuration in the lactam ring that apparently imparts resistance to lactamases. Substituents for the penicillin and cephalosporin families are shown in Figures 43-2 and 43-6, respectively. 

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