Synthesis and biological activity of novel cephalosporins containing a (Z)-vinyl dimethylphosphonate group

A series of cephalosporins containing a novel 7-[2-(Z)-(2-amino-thiazol-4- yl)-3-(dimethoxy-phosphoryl)-acryloylamino] group were prepared and their antibacterial activity measured against a range of pathogens. In general the compounds displayed a broad spectrum of activity against both Gram positive and Gram negative organisms, except Pseudomonas aeruginosa. Activity against the latter could be achieved by introducing a catechol moiety at the 3 position of the cephalosporin. The methyl phosphonates in general were stable to a wide range of beta-lactamases, including the TEM enzymes and the Enterobacter cloacae P99 chromosomal enzyme. In addition, they showed the advantage of being highly water soluble.