Reaction Of Cephalosporin Research Articles

Role of acetyl CoA: deacetylcephalosporin C acetyltransferase in cephalosporin C biosynthesis by Cephalosporium acremonium.

Existence of an acetyltransferase, which catalizes acetylation of deacetylcephalosporin C to cephalosporin C, was demonstrated for the first time in cell-free extracts of Cephalosporium acremonium. The pH optimum of the enzyme appeared to be 7.0 to 7.5 and the enzyme required essentially Mg2+ as a cofactor for its reaction. The activity of this enzyme was not observed in the cell-free extracts of deacetylcephalosporin C-producing mutants Nos. 20, 29, 36 and 40, but was recovered in a revertant obtained from the mutant No. 40. These results indicate that deacetylcephalosporin C accumulation by these mutants was due to the lack of the acetyltransferase and made it reasonable that the terminal reaction of cephalosporin C biosynthesis in Cephalosporium acremonium proceeded by the catalytic action of acetyltransferase.

Reaction of cephalosporins with N-bromosuccinimide

A 3-acetoxymethyl-Δ2-cephem derivative was converted into a 3-formyl-Δ2-cephem by oxidation with N-bromosuccinimide; a Δ3-deacetylcephalosporanic acid lactone formed a 2-bromo-derivative.

Products of aminolysis and enzymic hydrolysis of the cephalosporins.

1. The reaction of cephalosporins with ammonia, amino acids and other simple amino compounds in weakly alkaline aqueous solutions yields labile compounds with lambda(max.) 230nm. The reaction of deacetyl- and deacetoxy-cephalosporins under similar conditions yields compounds with lambda(max.) 260nm. 2. Hydrolysis with a beta-lactamase results in the formation of compounds with lambda(max.) 230nm from deacetylcephalosporins and cephalosporins, but not from deacetoxycephalosporins. 3. These different compounds decompose to give penaldates and penamaldates derived from the side chain and the carbon atoms of the beta-lactam ring. 4. Derivatives similar to those obtained with simple amino compounds appear to be formed when cephalosporins and their analogues react with lysine polymers. 5. Some of the chemical and physical properties of the various derivatives have been studied and tentative structures for them are proposed. 6. Possible implications of the results in relation to the immunological properties of the cephalosporins are discussed.

Changes in proton-magnetic-resonance spectra during aminolysis and enzymic hydrolysis of cephalosporins.

1. Changes in proton-magnetic-resonance spectra were followed during the reaction of cephalosporins, deacetylcephalosporins, deacetoxycephalosporins and a Delta(2)-cephalosporin with ND(3) in D(2)O. 2. Changes in proton-magnetic-resonance spectra were also followed during the hydrolysis of a cephalosporin and a deacetylcephalosporin in D(2)O with a beta-lactamase. 3. Structures for the reaction products are proposed. 4. The signals obtained after aminolysis of the beta-lactam ring of a cephalosporin indicate that the reaction is accompanied by expulsion of the acetoxy group as acetate, formation of a double bond in the Delta(4)-position and the appearance of an exocyclic methylene group. 5. Aminolysis of deacetyl- and deacetoxycephalosporins can occur without immediate structural changes in the dihydrothiazine ring. 6. In contrast, the ring structure of the first product of enzymic hydrolysis of a deacetylcephalosporin is apparently identical with that of the product of aminolysis of the cephalosporin itself.