Penicillin contains a strained ring. The strain in the four-membered ring increases the amide’s reactivity. It is thought that the antibiotic activity of penicillin results from its ability to acylate (put an acyl group on) a group of an enzyme that is involved in the synthesis of bacterial cell walls. Acylation inactivates the enzyme,and actively CH2OH growing bacteria die because they are unable to produce functional cell walls. Penicillin has no effect on mammalian cells because mammalian cells are not enclosed by cell walls. To minimize hydrolysis of the ring during storage,penicillins are refrigerated. Bacteria that are resistant to penicillin secrete penicillinase, an enzyme that catalyzes the hydrolysis of the ring of penicillin. The ring-opened product has no antibacterial activity.
More than 10 different penicillins are currently in clinical use. They differ only in the group (R) attached to the carbonyl group. Some of these penicillins are shown here. In addition to their structural differences, the penicillins differ in the organisms against which they are most effective. They also differ in their resistance to penicillinase. For example, ampicillin,a synthetic penicillin, is clinically effective against bacteria that are resistant to penicillin G, a naturally occurring penicillin. Almost 19% of humans are allergic to penicillin G. Penicillin V is a semisynthetic penicillin that is in clinical use. It is not a naturally occurring penicillin; nor is it a true synthetic penicillin because chemists don’t synthesize it. The Penicillium mold synthesizes it after the mold is fed 2-phenoxyethanol, the compound it needs for the side chain.