Chemistry of cephalosporin antibiotics. 28. Preparation and biological activity of 3 (substituted) vinyl cephalosporins

Article abstract of DOI:10.1021/jm00244a007

3 (Substituted)vinylcephem nuclei have been prepared by the reaction of 3 formylcephem derivatives with stabilized phosphoranes. Appropriate synthetic steps allowed preparation of a series of 3 ethoxycarbonylvinyl and 3 carboxyvinylcephem derivatives bearing a variety of 7 acylamino functions. The phenoxyacetyl and thiopheneacetyl derivatives of the 3 cyanovinylcephem nucleus were also prepared. Although general gram positive activity was comparable to cephalothin in many cases, against penicillin G resistant Staphylococcus aureus, the new cephalosporins were of low effectiveness. The 3 (substituted)vinyl cephalosporins had good activity against a number of gram negative organisms. In some cases, this activity was excellent. The N acetyl analogs had surprisingly good activity relative to N acetyl 7 ACA. The phenylmalonoyl side chain derivatives were shown to have an unusual antibacterial spectrum expansion (relative to previously known cephalosporins) to include activity against Serratia marcescens and Pseudomonas aeruginosa.