S-Lactam Antibiotics

Brooks G, Bruton G, Finn MJ, Harbridge JB, Harris MA, Howarth TT, Hunt E, Stirling I, Zomaya I (1985) In Brown AG, Roberts SM (eds) Recent advances in the chemistry of /S-lactam antibiotics. The Royal Society of Chemistry, London, p 280... 

Although most /S- lactam antibiotics bind covalently to some or all of the same six proteins, there are decided differences among them in terms of their relative affinities. For example, cefoxitin (see Table 1 for structures) fails to bind to protein 2 while cephacetrile binds very slowly to proteins 5 and 6. Cephaloridine binds most avidly to protein 1, the transpeptidase, and inhibits cell elongation and causes lysis at its minimum inhibitory concentration. On the other hand, cephalexin binds preferentially to protein 3 and causes inhibition of cell division and filament formation (75PNA2999, 77MI51002). 

Microbe Penicillin Bacterial infections (/S-lactam antibiotic)... 

Carbapenems are regarded as hopeful candidates for new-generation /S-lactam antibiotics (78JA6491 84H29). Thus, we applied our new chiral alkylation method to the synthesis of chiral / -substituted carbapenems and of the key intermediates for carbapenem syntheses. 

Woodward, R.B. (1977) in Recent Advances in the Chemistry of S-Lactam Antibiotics (Elks, J., ed.) Special Publication No. 28, The Royal Society of Chemistry, London, pp. 167-180. 

Azomethine ylides studied by Taylor et al. have the potential of allowing an entry into highly strained aza analogs of /S-lactam antibiotics (Scheme 128) (8UA7660). 

Aminoglycosides The aminoglycosides are important antimicrobial drugs used alone or in combination with )S-lactam antibiotics for the treatment of certain serious gram-negative infections. Chemically, the aminoglycosides consist of various sugars... 

The interactions of 8-lactams with PBPs indicate that these compounds are structural analogues of R-D-alanyl-D-alanine, the natural substrate of peptidoglycan transpeptidases and D-alanine carboxypeptidases, where R is the remainder of the pentapeptide. The mechanisms of the transpeptidase and carboxypeptidase reactions are thought to involve formation of an acyl-enzyme intermediate that can react with either a primary amine (e.g., an a-amino group) to form a peptide bond, or with water to form a carboxylic acid. In both reactions D-alanine is released before the acyl enzyme is formed. When a S-lactam antibiotic enters the binding site, the /1-lactam bond is hydrolyzed, and the resulting acyl group reacts with the active-site... 

S-Lactam antibiotics (78GEP2658906), quinazoline cardiac stimulants (83EUP94766), and antiparasitic nitroimidazoles (82IJC(B)941 84IJC(B)342) carrying a thiadiazolidine 1,1-dioxide-derived side chain have been reported. 

S-Lactam antibiotics, such as penicillin G, nafcillin, and ampicillin, remain the drugs of choice for streptococcal, staphylococcal, and enterococcal endocarditis, respectively. 

Azetidinones.—A considerable number of papers involving S-lactams have appeared again this year. Those concerned with /S-lactam antibiotics are not covered in this review except where interesting aspects of the construction or transformation of the azetidinone ring are involved. 

Lactam antibiotics, a family of antibiotics containing a -lactam ring (2-azetidinone). They are the most successful examples of natural product application and chemotherapy. Monobactams (name derived from monocyclic bacteriaUy produced /0-lactam antibiotics) are /S-lactam antibiotics, with only the lactam ring such... 

Oxidation of an allylic alcohol. This reagent has been used successfully to oxidize the benzyl ester of the /S-lactam antibiotic clavulanic acid (1) to the labile allylic aldehyde 2. Attempted oxidation with the Pfitzner-Moffatt reagent resulted in formation of a 1,3-diene by a 1,4-elimination. ... 

This new Specialist Periodical report combines the material previously reviewed in "Saturated Heterocyclic Chemistry", "Aromatic and Hetei oaromatic Chemistry", both of which are now discontinued, and "Organic Compounds of Sulphur, Selenium and Tellurium", which although still thriving has surrendered its heterocyclic parts but will continue to report on S-lactam antibiotic chemistry. The literature reviewed in this volume covers the period July 1978to July 1979. Brief Contents ... 

The prevalence of the carboxylate moiety in both biogenic and man-made molecules of interest makes this functional group a popular target for anion host chemistry. Needless to say, carboxylates are a major constituent of proteins, peptides and amino acids, and the expansion of proteomics begets increasing requirements for means of specific detection of such biomolecules. Other relevant examples of carboxylates include fatty acids, while many small molecule di- and tricarboxylates are implicated in key metaboUc pathways such as the citric acid cycle (e.g. citrate, succinate, fumarate and malonate). Carboxylated anthropogenic molecules include trichloroacetic acids, anionic surfactants and S-lactam antibiotics. 

Drawing mechanisms for two types of nucleophilic substitution in the same sequence to make a (S-lactam antibiotic. 

Nachr. Chem. Tech. Lab. 38/5, 616ff. (1990) Reuben Wittkoff, Pharmaceutical Chemicals in Perspective, New York Wiley 1989 Swartz, in Moo-Young (ed.). Comprehensive Biotechnology, vol. 3, p. 7-48, Oxford Pergamon Press 1985 see also /S-lactam antibiotics. - [HS 294110 CAS 1404-05-9]... 

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... 

Both, eukaryotic and prokaryotic microorganisms are able to produce )S-lactam antibiotics (Fig. 5.21).They may be divided into five classes corresponding to their core structures (Tab. 5.2). [26] Tab. 5.3 lists some of the most important intermediates and active compounds from the penicillin and cephalosporin... 

One of the most fascinating transformations in the biosynthesis of /S-lactam antibiotics is the key step of oxidative cyclisation by isopenicillin-N-synthase. Despite intensive searches for intermediates in the ring-closure reaction, enzyme-free monocyclic intermediates have never been found. It has been concluded, that both cyclisations occur within the same enzyme-substrate complex. Structural variations in the aminoadipoyl and (D)-valine moieties are well tolerated by the enzyme. On the other hand, cysteine cannot be altered. If the isopropyl group in valine is exchanged for an allyl or cyclopropylmethyl group, rearrangement products are found, which are typical of radical reactions. This indicates that an isopropyl radical is involved in the formation of the thiazolidine ring. 

When vinyl halide having the amino or the hydroxyl group in a tether was treated in a similar manner, mono- or bicyclic lactams and lactones could be synthesized. This method was further extended to the synthesis of /3-lactams 21 from 2-bromoallylamine derivatives 20 (Scheme 6). ° Using this novel /3-lactam synthesis, 3-anunonocardicinic acid (3-ANA, 23), which is a core part of a monocyclic /S-lactam antibiotic, nocardicin A (22), could be synthesized from... 

Spray with 5% potassium permanganate Before the coating, the silica gel plate was activated by heating for 15 min at 110°C, /S-lactam antibiotics were dissolved in distilled water to give about 3 mg/ml, and about 1 />1 of soln. was spotted on the thin-layer plate... 

C. Resistance to S-lactam antibiotics(penicillins and ceohalosixjrins) has been extensivei.y stuaiea, since it has significantly dictated the application and use of antibiotics of this class. With one notable exception (methicillin resistance in Staphylococcus) resistance to these antibiotics... 

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