Abstract
A number of new optically active 1-oxacephem compounds were synthesized and tested for antibacterial activity. Various 7α-unsubstituted 1-oxacephem nuclei 2a-e and a 7α-methoxy-1-oxacephem nucleus 3, reported previously, were converted into the corresponding phenylacetylamino-, 2-thienylacetylamino-, D-mandelylamino-, D-phenylglycylamino-, and arylmalonylamino-1-oxacephem carboxylic acids. All the compounds except for the phenylglycylamino derivatives exhibited four- to sixteen-fold enhanced antibacterial activity compared with that of the corresponding cephalosporins. A combination of the 7α-methoxy-3-(1-methyl-1Htetrazol-5-yl)thiomethyl-1-oxacephem nucleus and a 7β-arylmalonylamino side chain, as represented by compound 1 (disodium salt of 33), produced the highest efficacy among them: high antibacterial activity with a widely expanded spectrum against Gram-negative bacteria including resistant strains and Pseudonronas aeruginosa was observed.
