Penicillin’s and other fl-lactam antibiotics (see the Focus On in this chapter) typically develop a resistance to bacteria due to bacterial synthesis of β-lactamase enzymes. Tazobactam, however, is able to Inhibit the activity of the -1actamasc by trapping it, (hereby preventing resistance from developing.

(a) The first step in trapping is reaction of a hydroxyl group on the p-lactamase to open the /3-lactam ring of Tazobactam. Show the mechanism.

(b) The second step is opening of the sulfur-containing ring in Tazobactam to give an acyclic iminium ion intermediate. Show the mechanism.

(c) Cyclization of the iminium ion intermediate gives the trapped β-lactamase product. Show the mechanism.

Transcribed Image Text:

Enz Nú SO2 N=N Nu Enz "CHз он H-N CHз CO2H CO2H Tazobactam Trapped B-lactamase B-Lactamase