Coupling Reactions of Cephalosporin Sulfones: A Stable 3-Stannylated Cephem (original) (raw)

The first stable 3-metalated cephalosporin is reported and shown to be an excellent synthetic precursor to a number of prospective-lactamase inhibitors. One highly effective method for countering antibioticresistant microorganisms is the co-administration of an antibiotic and a-lactamase inhibitor. 1-Lactamase represents a collection of bacterial enzymes (classes A, B, C, and D) that effectively hydrolyze-lactam antibiotics. Historically, the most clinically important of these were the plasmidmediated class A enzymes. 2 However, in recent years, bacterial resistance mediated by class B, C, and D enzymes has become increasingly significant. 3 Current commercial inhibitors target only class A-lactamases. 1 Our group has recently described classes of compounds that simultaneously inhibit both class A and class C-lactamases. 4 We have designed new inhibitors both of the penicillin and of the cephalosporin skeleton. Unlike the corresponding penicillin and cephalosporin antibiotics, however, these new compounds have the sulfur in the sulfone oxidation state and have an alkylidene side chain in place of the more common acylamido side chain at C6 (penam) or C7 (cephem). Some examples are shown in Figure 1. Figure 1. Representative-lactamase inhibitors containing an R-alkylidene-lactam substructure.