Cephalosporin analogs

Early attempts to produce cephalosporin analogs by varying the 7-acylamino substituent were frustrated because, in contrast to previous experience with penicillins, a good method for producing the necessary 7-amino compound (33a) could not be found. This problem was finally solved when it was discovered that diazotization of the a-aminoadipyl residue produces an iminolactone (33b) which can be hydrolyzed to the free amine in good yield. Subsequently an improved procedure was developed which involves silylation of the carboxyl groups followed by reaction with phosphorus pentachloride to yield iminochloride (33c)... 

Scheme 13 Organonickel and organopalladium mediated routes of cephalosporin analogs and indoles.

Particular attention has been focused on cycloadditions of acid chlorides bearing a masked amine func-tion since they are potential precursors of penicillin or cephalosporin analogs (equations 23-27). 

Cephalosporin analog elastase mechanism-based some cross-reactivity 161,000 M-is-i (48)... 

III. Electrogenerated Triphenyltin Access to Thiyl Radicals and Cephalosporin Analogs... 

III. ELECTROGENERATED TRIPHENYLTIN ACCESS TO THIYL RADICALS AND CEPHALOSPORIN ANALOGS... 

CV studies indicate that Ph3SnY, where Y = Cl, OTf, OCHO, SnPh3, do not serve as a source of the triphenyltin radical because in these instances the radical is generated at potentials where it is either oxidized or reduced [19]. Reaction of the triphenyltin radical with an alkyl halide or a disulfide produces a carbon- or a sulfur-centered radical, respectively. Use of the latter transformation in conjunction with a subsequent intramolecular cyclization onto an alkene is nicely illustrated by the conversion of /6-lactam 62 to the cephalosporin analog 63. 

Cephalosporins are important (f-lactams, but a number of pathogenic microorganisms have developed resistance to these antibiotic compounds. In order to prepare novel antibiotic cephalosporin analogs, I. Chao and co-workers synthesized 1-dethia-3-aza-1-carba-2-oxacephem, which is not a substrate of the inducible 3-lactamase enzyme. The key step of the synthetic sequence was the Barton nitrite ester reaction in which regioisomeric oximino 3-lactams were generated and transformed into the desired product. ... 

In addition to the several examples mentioned above, the syntheses of the following natural products and related compounds via Pd-catalyzed allylation have been reported, and they are summarized in Sect, in.2.18 ( )-neomanoalide, vineomycinone B2 methyl ester, cephalosporin analogs,hennoxazole stypoldione, 6-keto-prostanoids, constanolactones A and lurlene, lurlenic acid, and lurlennlJ " ... 

Reaction of 7-amino-3-[5 -methyl-r,3 ,4 -thiadiazol-2 -ylthiomethyl] cephalosporanic acid with heterocyclic amines using basic alumina under microwave irradiation (MWI) afforded new cephalosporin analogs in shorter reaction time with improved yield as compared to conventional heating (Scheme 56). ... 

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