Design And Synthesis New β-Lactamase Inhibitor Of Lead Compounds

β-lactam antibiotics play a central role in the treatment of bacterial infections.β-lactamase are the primary cause of resistance against most widely used β-lactamantibiotics. These enzymes efficiently hydrolyze the amide bond of the β-lactam ring togive products that are devoid of antibacterial activity. Therefore, the administration of aβ-lactamase inhibitor along with an antibiotic represents an important strategy forcombating the resistance against these drugs. Clavulanate, sulbactam and tazobactam arethree currently marketed β-lactamase inhibitors. Unfortunately, these commericalβ-lactamase inhibitors have little or no activity against class C enzymes. They also haveno activity against metallo-β-lactamase. Therefore, design and synthesis novel β-lactamaseinhibitors is imperative.The paper upon reviewing the species and application of the β-lactamase, thenintroduced the known β-lactamase inhibitors, the new β-lactamase inhibitors and themethods that evaluated the β-lactamase inhibitors. Most of the clinically used β-lactamaseinhibitors are penicillins and cephalosporins, they are bicyclic compounds with adjacentfive or six-member ring on the beta lactam core containing a heteroatomic ring atomconstituent. These compounds that containing beta lactam could be easily identified byβ-lactamase. As a β-lactamase inhibitor carboxy is the essential group to them. Theintroduction of rigidity into beta lactam (for example double bond) might reduce itsstability and improve the binding. Based on these theories, we designed and synthesized97-sulfenimines cephalosporins through the way that introduce different sulfeniminesground at position7on cephalosporin nucleus (7-ACA,7-ANCA,7-APCA and7-TMCA).All the target compounds were identified by~1H-NMR and IR. The known sulfeniminescompounds were found to inhibit β-lactamase at micromolar level, these compounds maybecome a novel β-lactamase inhibitor.Different cephalosporins were suspended in methylene chloride andBis(trimethylsilyl)trifluoroacetamide was added. Sulfenyl bromine in methylenechloride was added dropwise to form the structure of sulfenimine precursors bysubstituted-elimination of7-amino. The target compounds were isolated by hydrolysis orin the form of sodium salt.