Cephalosporins tricyclic

Further, the discovery of 7-a-methoxy cephalosporins [5] from Streptomyces in 1971, carbapenems [6], thienamycin [7], clavulanic acid [8], sulbactum [9] as well as the totally synthetic oxapenems [10], oxacephams [11], and other bicyclic (3-lactams stimulated the search for novel antibiotics. More recent dedicated efforts to find new active molecules and modify the penicillin and cephalosporin structure have resulted in the discovery of simple monocyclic (3-lactams such as norcardicins and monobactams [12, 13]. Yet another dimension has been added to the (3-lactam research with the recent discovery of tricyclic (3-lactam antibiotics called trinems [14]. Thus, (3-lactam antibiotics in general can be classified into several groups based on their structures (Fig. 1). 

C(2)-C(3) fused polycyclic cephalosporins have received considerable attention as new candidates for /3-lactam antibiotics. An access to tricyclic cephalosporins based on metal-promoted alkenylation of 3-trifloxy-A3-cephem and subsequent Diels-Alder reaction has been published <1996TL5967>. Alternatively, the reaction of a cephalosporin triflate with silyl enol ethers and silylketene acetals has been described to afford tri- and tetracyclic cephalosporins <1996TL7549>. A related process is the formation of fused polycyclic cephalosporins 27 and 28 bearing a wide range of functionalities from the reaction of cephalosporin triflates 26 with unsaturated compounds (alkenes and alkynes) and a base (Scheme 5) <1997JOC4998>. These studies have suggested that the reaction proceeds via the intermediacy of a six-membered cyclic allene which undergoes concerted nZs + K2a cycloaddition with alkenes and acetylenes. 

Aztreonam - intramuscular or intravenous - is excreted unchanged by glomerular filtration and renal tubular secretion. It lacks the allergenic tricyclic nuclear structure of penicillins, cephalosporins and carbapenem beta-lactams. 

Table 8.5. IN VITRO ANTIBACTERIAL ACTIVITY OF DIFFERENT 2-SUBSTITUTED CEPHALOSPORINS AND TRICYCLIC ANALOGUES [53] MEASURED AS ZONE DIAMETERS IN MILLIMETERS ...

Table 8.9. IN VITRO ANTIBACTERIAL ACTIVITY OF 3,4-TRICYCLIC CEPHALOSPORINS [86] (MINIMUM INHIBITORY CONCENTRATION, iigim])...

Other examples are found in the neuroleptic or antidepressant tricyclics, in the benzodiazepine tranquillizers and antiepileptics, and in the development of semi-synthetic penicillins and cephalosporins with broader spectra of activity and greater stability towards 3-lactamases. In some instances an aromatic ring can be replaced by an ethynyl group. Such a replacement was recently described by... 

Wittig reactions of the (R)- or (S)-isomers of the aldehyde (263), readily available from serine, provide the alkenes (264) and hence the vinyl glycines (265) with defined configuration and double bond geometry (Scheme 21). 55 The reaction of cephalosporin 3 -triphenylphosphorane (266) with a-halogenoketones has been used to synthesize new tricyclic cephalosporins (267). 56 One-pot coupling of the phosphonium salt (268)... 

A rather distant tricyclic analogue of cephalosporins, (180), was obtained by cycloaddition of a mixed anhydride to a bicyclic imine [112). The synthesis of... 

A carbon analogue of penicillin V (Ic) was resistant to Bacillus cer-eus B l ctamase and moderately active against gram-positive organisms.6 ) Several 2-acetoxymethyl penicillins (2ja,y6 and 2-spirocyclopropyl cephalosporins (3 )65 vere prepared. Various chemical procedures were developed for the 7(6)a-methoxylation of B-lactam antibiotics.66-72 Conversion of penicillins to cephalosporins was achieved by new synthetic routes.73-76 Some [2,3]-fused tricyclic cephem derivatives (4a-c) were synthesized.77,78 Compound displayed significant antibiotic activity.78 Racemic cephalothin, 7-methoxycephalothin, and cefoxitin were obtained by total synthesis of a novel type.79-81 nuclear analogue of a 7-methylcephalosporin (5), prepared by total synthesis, lacked antibiotic activity,82... 

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