Cephalosporin skeleton

The strained structure of carbapenems confers a higher reactivity to the carbapenem skeleton than that of cephalosporin skeleton. It has been suggested that both p-lactam ring and the basicity of C-2 side play a major role in carbapenem-induced nephrotoxicify [70]. 

A study of the cephalosporin skeleton reveals that cephalosporins can be derived from the same biosynthetic precursors as penicillin, i.e. cysteine and valine (Fig. 10.42). 

The assimilation of cysteine into the penicillin skeleton occurs with loss of the 3-pro-5-hydrogen atom. Examination of the closely related cephalosporin skeleton [as (166)] has shown that it too is formed from cysteine with loss of the 3-pro-5-proton, and consequently retention of configuration at this centre, which... 

Modification at C-2 of the cephalosporin skeleton has attracted limited interest, since those transformations which have been reported have not led to products with significantly improved antibiotic properties. Low-temperature methyl-thiolation of cephem sulphoxide (58) via its C-2 anion afforded thiomethyl derivative (59). The reaction proceeded stereospecifically from the least hindered side to give the a-isomer exclusively. When the reaction was carried out at a somewhat higher temperature (- 23 °C), the bis(methylthio)-compound... 

Steroid Antibiotics. The steroid antibiotics are a stmcturaHy diverse class of steroids that have a common biological function, ie, antibacterial, antifungal, antiviral, or antitumor activities. This group of compounds can overlap with other steroid classes Hsted above. Eusidic acid [6990-06-3] (67), helvohc acid [29400-42-8] (68), and cephalosporin [13258-72-5] (69) exemplify a set of antibacterial steroids that contain a prolanostane skeleton with an... 

F i g U re 2 3.2 Structural skeletons for the principal classes of -lactam antibiotics. For example the penicillins are all penams and the cephalosporins are all cephems. 

Cephalosporin one of an important class of antibacterials based on the cephem skeleton. 

The fused 0-lactam skeletons found in penicillins and cephalosporins are termed penam and... 

Correct answer = A. Most urinary tract infections are due to E. coii and can usually be treated with cotrimoxazole. However, this patient is near term and the sulfa in the cotrimoxazole might put the infant at risk due to kernicterus. Thus, the first generation cephalosporin, cefadroxil, is appropriate since it would be effective orally against penicillinase producing E. coii. Ceftriaxone, while it would be effective, would have to be administered parenterally. Penicillin V is not effective against E. coii. Tetracycline deposits in teeth and skeleton of the fetus and is contraindicated. 

Ylides with substituted carbanions can form vicinal stereocenters upon 2,3-reairangement. In acyclic compounds, little stereocontrol is documented more often than good control. Cyclic ylides, on the other hand, exhibit high stereoselectivities for ring contractions via 2,3-sigmatropic shifts. The oldest and still the most impressive among such reactions is Yoshimoto s transformation of the cephalosporin (162) into the penicillin skeleton (163). Diastereoselectivity follows from an exo preference of the ester group in transition state (164 equation 49). ... 

Access to analogues with varied side-chains at the 7-position initially posed a problem. Unlike penicillins, it proved impossible to obtain cephalosporin analogues by fermentation. Similarly, it was not possible to obtain the 7-ACA (7-aminocephalosporinic acid) skeleton (Fig. 10.44) either by fermentation or by enzymic hydrolysis of cephalosporin C, thus preventing the semisynthetic approach analogous to the preparation of penicillins from 6-APA. 

In general, cephalosporins have lower activity than comparable penicillins, but a better range. This implies that the enzyme which is attacked by penicillin and cephalosporin has a binding site which fits the penam skeleton better than the cephem skeleton. 

Helvolic acid (164) originally isolated from Aspergillus fumigatus has also been identified in Gliocladium species where it cooccurs with the 1, 2-dihydro analogue [59]. Helvolic acid shares the unusual tetracyclic triterpene skeleton of the fusidanes with fusidic acid and the cephalosporin Pi and all show antibacterial activity [230, 231]. 

In spite of the above mentioned limitations, it should be noted that a lot of carbon-carbon and carbon-heteroatom coupling reactions have been summarized in this review. These reactions have given rise to about 200 new compounds in recent years. Complexes 111, 115, and 116 containing an azetidine skeleton or the 1,3-thiazinyl derivatives 98-100 are of particular interest. In this respect, it should be mentioned that as a consequence of the discovery of the cephalosporins and the enormous development occurring in the chemistry of these antibiotics since the 1940s, the 1,3-thiazine nucleus has became one of the most important six-membered heterocycles [90]. 

The bicyclic skeletons of both the penicillins and cephalosporins can formally be divided into amino acid components, as shown by (291) and (292) this is of importance as regards the tripeptide theory. 

The incorporation of and stable isotope labelled precursors into the molecule of cephalosporin C (27) is illustrated in Scheme 1.4. The reader is referred to the original papers for the detailed procedures and discussion of the results. Information on the incorporation of [ Cjacetate and various [ C]-valines was obtained from C-NMR studies of cephalosporin C after incubation of the culture with the appropriately labelled precursor [204,209—212]. Most of the side chain carbon atoms where shown to be derived from acetate residues by feeding sodium [l- C]acetate and sodium [2- C]acetate [209,210]. The incorporation of the entire valine skeleton into both penicillin N and cephalosporin C was shown by the use of (2535)-[ N-(3-meiAy/-D3)]valine [213). The... 

There is a wide variety of metabolites containing nitrogen, which is produced by micro-organisms. The nitrogen atom (or atoms) most frequently is derived ultimately from an a-amino acid which also provides at least part of the carbon skeleton. Modifications to cyclic dipeptides are commonly encountered as secondary metabolites (Sections 7.3 and 7.4). In the case of the vastly important pharmaceuticals, the penicillins and cephalosporins (Section 7.6.5), a linear tripeptide is involved in biosynthesis. 

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