It is formed by acylases that cleave off the side chain of the penicillins, and can also be
obtained by the selective chemical cleavage of the amide, leaving the lactam intact.
After this, 6-APA can be easily acylated by any carboxylic acid, and this has yielded
literally thousands of semisynthetic penicillins in the past 30 years, many showing
improved stability and activity. Some of them are lactamase resistant (methicillin
(9.41), oxacillin (9.42) and its halogenated derivatives), whereas others are broad-
spectrum antibiotics, like the orally active ampicillin (9.43), which also inhibits Gram-
negative bacteria but is sensitive to lactamase. Carbenicillin (9.44) is particularly active
againstPseudomonasandProteusinfections, which are unaffected by “natural” peni-
cillins. Piperacillin (9.45), a broad-spectrum compound, is spectacularly active against
Pseudomonas.
9.4.1.2 Cephalosporins
The cephalosporins, discovered in the 1950s, are produced by various species of the mold
Cephalosporium. Cephalosporin C (9.46) is the prototype of these antibiotics, and its
structure shows a close similarity to the penam structure. The 5-thia-1-azabicyclo[4.2.0]
octane ring system is therefore called the cepham ring. The parent compound carries the
aminoadipate side chain, which can be cleaved to supply the 7-amino-cephalosporanic acid.
This amine can easily be acylated and thus forms the basis of many useful derivatives. The
3-acetoxymethyl substituent is also amenable to modifications.
EXOGENOUS PATHOGENS AND TOXINS 567