Beta-lactams formation

Lynch JE, Riseman SM, Laswell WL, Volante RP, Smith GB, Shinkai I, Tschae DM. Mechanism of an acid chloride-imine reaction by low-temperature FT-IR beta-lactam formation occurs exclusively through a ketene intermediate. J. Org. Chem. 1989 54 3792-3796. 

For example, Escherichia coli have six PBP. PBP-la and -lb, which are transpepfidases, are involved in the synthesis of peptidoglycan. PBP-2 is necessary for supporting the rodshaped form of bacteria. Selective inhibition of this enzyme causes production of other non-rod-shaped forms of bacteria, which eventually undergo lysis. PBP-3 is necessary to form the partition during division. Selective inhibition of this enzyme leads to the formation of a fibrous form of bacteria containing many units of rod-shaped bacteria unable to separate one from another, which results in their death. Various beta-lactam antibiotics have a selective affinity to one or a few PBP. Inactivation of certain PBP (PBP-la, -lb, -2, or -3) causes cell death. Unlike these, inactivaition of low-molecular PBP (PBP-4, -5, and -6) is not lethal to bacteria. 

The first completely synthetic monocyclic beta-lactam antibiotic was aztreonam. The antimicrobial activity of this drug is exhibited mainly with respect to a broad spectrum of aerobic Gram-negative bacteria. It is resistant to beta-lactamases and does not induce their formation. The mechanism of its action is identical to that of other beta-lactam antibiotics with respect to Gram-negative bacteria. PBP are inactivated in the presence of aztreonam. 

It is believed that the methyl group at position 4 increases the stability of the beta-lactam ring with respect to most beta-lactamases, and at the same time it does not induce formation of beta-lactamase as cephalosporins and imipenems do. 

Thiadiazole, formation, 312, 313, 445 Thiazole formation bromoester, 298-304 bromoketone, 565 Thiazolidinone formation beta lactam, disulfide cleavage, 552 nitrile addition, 301 Thiehopyridine formation, 586 Thienothiazinol formation, 593 Thioacetal formation, 130, 185, 248 glyoxylate, 355 ethyl mercaptopropionate, 447 Thioacid formation, thioformamidoyl chloride, 184... 

Beta-lactam penicillins prevent the biosynthesis of a dipeptidoglycan which forms the peptidoglycan cell wall in bacteria. This results in cell death and bactericidal activity. Specifically, they acylate a specific bacterial D-transpeptidase, which inactivates this enzyme and it therefore cannot form peptide crosslinks of two linear peptidoglycan strands for cell wall formation. 

Gastrointestinal upsets, nausea, and vomiting have been observed with virtually all beta-lactam antibiotics, both oral and parenteral. Even when comparing analogous applications and doses, no particular risk can be clearly ascribed to a given compound. Acute hemorrhagic colitis without pseudomembrane formation has been described after treatment with various penicillins and cephalosporins (SEDA-21, 261). 

Non-IgE-antibody-mediated immunological reactions Modification of erythrocyte surface components due to binding of beta-lactams or their metabolic products is thought to be the cause of the formation of antierythrocyte antibodies and the development of a positive Coombs test implicated in the development of immune hemolytic anemia (211). About 3% of patients receiving large doses of intravenous penicillin (10-20 million units/ day) will develop a positive direct Coombs test (212). However, only a small fraction of Coombs positive patients will develop frank hemolytic anemia (213). Antibody-coated erythrocytes are probably eliminated by the reticuloendothelial system (extravascular hemolysis) (214), or less often by complement-mediated intravascular erythrocyte destruction (215). Another mechanism implicates circulating immune complexes (anti-beta-lactam antibody/beta-lactam complexes), resulting in erythrocyte elimination by an innocent bystander mechanism (82). Similar mechanisms have been implicated in thrombocytopenia associated with beta-lactam antibiotics (216,217). 

Beta-lactam-induced generation of superoxide and hydrogen peroxide triggers formation of further highly... 

Imada, A, Kintaka, K, Nakao, M, Shinagawa, S, Bulgecin, a bacterial metabolite which in concert with beta-lactam antibiotics causes bulge formation, J. Antibiot., 35, 1400-1403, 1982. 

Beta-lactam-induced generation of superoxide and hydrogen peroxide triggers formation of further highly reactive and cytotoxic oxygen species such as hydroxyl radical. Hydroxyl radical can further contribute in the presence of iron salts, to the decomposition of hydro-... 

Enzymatic hydrolysis of the beta-lactam ring results in loss of antibacterial activity. The formation of beta-lactamases (penicillinases) by most staphylococci and many gram-negative organisms is thus a major mechanism of bacterial resistance. Inhibitors of these bacterial enzymes (eg, clavulanic acid, sulbactam, tazobactam) are sometimes used in combination with peni-... 

Schneider CH, de Week AL (1981) Allergy towards )S-lactam antibiotics. In Mitsuhashi S (ed) Beta-lactam antibiotics, JSSP. Springer, Berlin Heidelberg New York, p 299 Schneider CH, de Week AL, Stauble E (1971) Carboxy-methylcellulose. Additives in penicillins and the elicitation of anaphylactic reactions. Experientia 27 167 Schneider CH, Pfeuti C, de Week AL (1973) Aspects of formation of the D-penicillamine antigenic determinant from penicilloyl compounds. Helv Chim Acta 56 1235 Schneierson SS, Perlman E, Shore B (1964) Cephalotin antigenicity and cross-reactivity with penicillin G. Clin Med 71 1933... 

Antibiotics The AOAC has listed methods for sulfamethazine residues in swine tissues with determination either by GC-MS or GC-ECD of methylated derivatives and for sulfamethazine (and for the class of sulfonamides) in milk with determination by HPLC-UV. There is an AOAC method for the class of sulfonamide antimicrobials in animal tissues using solvent extraction and liquid partitioning with determination by TLC and fluorimetric scanning. For analysis of tetracyclines, AOAC describes methods based on buffer extraction from tissue samples and SPE (Cis) cleanup, or metal chelate affinity binding from milk samples, with determination in both cases by HPLC-UV. USDA/FSIS methods include (1) a method (similar to the AOAC GC-MS method for sulfamethazine) for confirmation of sulfonamide residues in edible tissues using solvent extraction and multiple liquid partitioning with determination of the methylated derivatives by GC-MS (2) methods for determination and confirmation of chloramphenicol in muscle by solvent extraction, liquid partitioning, and determination of the trimethylsilane (TMS) derivative by GC-ECD and GC-MS, respectively and (3) a method for determination of the beta-lactam antibiotic amoxicillin by aqueous extraction, cleanup by tricarboxylic acid precipitation, and ether extraction and formation of a fluorescent derivative for determination by LC. 

The oxidation of the sugar-containing carboxylic acid 52, in the presence of acetate, leads to the unsymmetrical bis-acetal 53 [30]. In a similar manner, 0,N-acetals can be efficiently constructed from alpha-amino-acids [24]. This process has been employed as a key step in the synthesis of some beta-lactam antibiotics [31]. The oxidative decarboxylation of alpha-alkoxy acids 58 in methanol provides a simple and efficient route to the formation of MOM ethers and obviates the use of the highly toxic MOMCl [32]. Furthermore, Mark6 et al. demonstrated that Hofer-Moest reaction of dialkoxy carboxylic acids 60 offers an easy and general route to variously functionalized orthoesters [33]. These are usually difficult to prepare by alternative methodologies and some of them can only be assembled using this electrochemical process. 

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