Conjoint molecules of cephalosporins and aminoglycosides

A general synthetic route to conjoint molecules of cephalosporins and amino glycosides is described. These molecules were designed as potential substra tes for bacterial beta -lactamases, enzymes that hydrolyze the beta -lactam bond of cephalosporins. Hydrolysis of the beta -lactam bond was expected t o release the Clo-appended aminoglycoside. Since beta -lactamases are seque stered in the periplasmic space of gram-negative bacteria, this sequence of events would liberate aminoglycoside inside such bacteria. It is expected that such local delivery of aminoglycosides would circumvent the inherent t oxicity of aminoglycosides that occurs during systemic exposure within the mammalian host.