Amino-beta-lactams

An active dipeptide transport system that depends on hydrogen ions takes up non-ester amino-beta-lactams (penicillin, amoxicillin, and oral first-generation cephalosporins) (337-339) and specific cephalosporins that lack the alpha-amino group (cefixime, ceftibuten, cefdinir, cef-prozil) (340,341). Nifedipine increases amoxiciUin and cefixime absorption, probably by stimulating the dipeptide transport system, since the serum concentrations of passively absorbed drugs and intestinal blood flow did not change (342-344). 

ANTTBIOTTCS - BETA-LACTAMS - MONOBACTAMS] (Vol 3) l-Amino-2,7-naphthalenedisulfomc acid [486-54-4]... 

G. L., Characterization of the oral absorption of some beta-lactams effect of the alpha-amino side chain group,... 

Chemical or enzymatic hydrolysis of this compound allows to obtain large quantities of 7-aminocephalosporanic acid. A number of semisynthetic beta-lactam cephalosporin antibiotics were created by acylating the amino group of the last with various acid derivatives (analogous to the semisynthetic penicillin series) and currently there are about 25,000 of them, of which about 100 are used in medicine. Unlike penicillins, semisynthetic cephalosporins are synthesized not only by expanding the spectrum of various acids by which 7-aminocephalosporanic acid is acylated, but also by internal modifications of aminocephalosporanic nucleus (Rj and Rj). 

Beta lactam antibiotics having a (3-lactam ring, which includes penicillin, in which a thiazolidine ring is attached to a betalactam ring that carries a secondary amino group. Other similar compounds are cephalosporins, monobactams and carbapenems. 

Bose, A.K., Banik, B.K., Mathur, C., Wagle, D.R. and Manhas, M.S., Polyhydroxy amino acid derivatives via beta-lactams using enantiospecific approaches and microwave techniques, Tetrahedron, 2000, 56, 5603. 

Amino acids, peptides, and proteins Asymmetric synthesis and induction Beta-lactam antibiotics Carbohydrates (chemical aspects) Natural product synthesis New antibiotics... 

Penicillinase. Cephalosporinase. A beta-lactam + H(2)0 = a substituted beta-amino acid. 

Scheme 19.17 Nucleophilic opening of penicillin s beta-lactam. This process occurs under basic conditions and is driven by the energetics associated with relieving the considerable bond-angle strain present in the 4-membered-ring. Two pathways are shown (i) The top results in acylation of a biological surface that has a good nucleophile such as the terminal amino-group on a lysine amino acid residue and, (ii) The lower represents a ready hydrolytic ring-opening by a water molecule to produce an inactive degradation product called penicilloic acid.

This newer analytical approach could effectively replace any need for reductive LCEC in the future, since it appears that most compounds already studied by reductive means can now be done by oxidative HPLC-hv-EC methods as well. This has Included compounds such as 1) organic nltro derivatives, C-nltro, 0-nitro, N-nitro, etc. 2) M-nltroso compounds, such as N-nltrosamlnes, N-nltroso amino acids, etc. 3) organothlophosphates, such as malathlon, parathion, ethion, etc. 4) aromatic esters and amides, such as benzamlde, vitamin B, alkyl benzoates, etc. 5) beta-lactams, such as penicillins and cephalosporins 6) mycotoxlns, such as vomltoxln or deoxynlvalenol ... 

Kim MG, Lee SB (1996) Penicillin acylase-catalyzed synthesis of P-lactam antibiotics in water-methanol mixtures effect of cosolvent content and chemical nature of substrate on reaction rates and yields. J Mol Catal B Enzym 1 201-211 Kohsaka M, Domain AL (1976) Conversion of penicDlin N to cephalosporin(s) by ceU-free extracts of Cephalosporium acremonium. Biochem Biophys Res Commun 70(2) 465-473 Koreishi M, Tani K, Ise Y et al. (2007) Enzymatic synthesis of P-lactam antibiotics and /V-fatty-acylated amino compounds by the acyl transfer reaction catalyzed by peniciUin V acylase from Streptomyces mobaraensis. Biosci Biotechnol Biochem 71(6) 1582-1586 Kupka JY, Shen, YQ, Wolfe S et al. (1983) Partial purification and properties of the alpha-ketoglutarate-linked ring expansion enzyme of beta-lactam biosynthesis of Cephalosporium acremonium. FEMS Microbiol Lett 16 1-6... 

O Boyle NM, Greene LM, Keely NO, Wang S, Cotter TS, Zisterea- DM, Meegan MJ (2013) Synthesis and biochemical activities of antiproliferative amino acid and phosphate derivatives of microtubule-disrupting beta-lactam combretastatins. Eur J Med Chem 62 705-721... 

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. 

The monobactams have a single beta-lactam ring structure. The only clinically used monobactam is aztreonam. Replacement of the 1-sulfonic acids residue in monobactam with an Af-sulphonylated carbonyl amino moiety yields monocarbams [71, 72 ]. So far, however, no monocarbam derivative is on the market, probably because their antimicrobial moiety is not optimal. Since micro-organisms need iron for growth, some siderophore-conjugated monocarbams are now under evaluation [73 ]. It is reasonable to assume that it will take some time until they are marketed. One of the many problems not yet solved is the in vivo fate of the siderophore itself, since it may create some new adverse effects of its own. 

The widespread use of penicillin eventually led to a clinical problem of penicillin-resistant staphylococci and streptococci. Resistance for the most part involved the penicillin-destroying enzyme, penicillinase, which attacked the beta-lactam structure of the 6-amino-penicillanic acid nucleus (6-APA). 

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