Penicillin G (Figure 9.2) was the rst β-lactam antibiotic that entered the clinic. It has a bicyclic structure consisting of a four-member β-lactam ring and a vemember hydrothiazole ring. The activity of these antibiotics is related to the opening of the ß-lactam ring. A large ring strain leads to both its high antibacterial potency and its instability under acidic and basic conditions.