Cephalosporanic acids. Part IV. 7-Acylamidoceph-2-em-4-carboxylic acids

Abstract

The combined action of bases and acid anhydrides on 7-acylamidocephalosporanic acids, and the action of bases on their esters, set up equilibria in which the corresponding A2-isomers predominate. The isomerisation represents a prototropic shift probably favoured by the sulphur atom in the dihydrothiazine ring. The acetoxy-group in the A2-compounds can be replaced by nucleophiles.Treatment of methyl 3-acetoxymethyl-7~-phenylacetamidoceph-3-em-4-carboxylate 1 [-oxide with a base res u I ts i n d eca rboxy I a t i o n . Attempts to prepare 7 pp he n y I a ceta m i d o ce p h -2 -em -45car boxy I i c acid 1 toxi d e resulted in formation of its A3-isomer and some carbon dioxide.

Hetacillin: A Chemical and Biological Comparison with Ampicillin

“…Furthermore, the fact that hetacillin does not react with hydroxylamine at pH 7 implies that the /3-lactam ring is relatively unreactive, which again would suggest a low level of antibacterial activity, since it is thought that a high reactivity of the /3-lactam bond is a prerequisite for the mode of action of penicillins. Dihydrocephalosporins and A 2 cephalosporins, both of which have negligible biological activity, are similarly unreactive with hydroxylamine at pH 7, while the biologically active penicillins and cephalosporins readily form hydroxamates under such conditions [1,7].…”

.BETA.-Lactam antibiotics derived from nitrogen heterocyclic acetic acids. 2. Cephalosporin derivatives.

“…3-Acetoxymethyl-7-[2-(4-oxo-l (4H)-pyridinyl) acetyl] amino-8-oxo-5-thia-l -azabicyclo [4.2.0] oct-2-ene-2-carboxylic acid, sodium salt (2) Method A A mixture of 1 (6.2 g, 0.04 mole), CD[ (7.8 g, 0.048 mole) and 75 ml of dry DMF was stirred for 1 hour under a dry nitrogen atmosphere. At the end of this period the reaction mixture consisted of a thick white suspension of the imidazolide.…”

Experimental and theoretical investigations on the cephalosporin Δ3Δ2 isomerization

“…The conversion of ∆ 3 cephalosporin derivatives into the ∆ 2 isomers was first described by Green and coworkers [9] and Cocker and coworkers [10] who observed that ∆ 3 acids undergo slow isomerization in pyridine, while the corresponding esters and anhydrides are isomerized more rapidly [11,12]. Subsequently Morin et al [13] found that while alkyl 3-acetoxymethyl-7-acylamino-3-cephem-4-carboxylates give a 7:3 (∆ 2 :∆ 3 ) equilibrium mixture, this ratio is completely reversed for the 3-methyl analogues.…”