Chemistry of -Lactams

It is over sixty years since Alexander Fleming observed antibiosis between a Penicillium mould and bacterial cultures and gave the name penicillin to the active principle.

Although it was proposed in 1943 that penicillin (1) contained a tJ-Iactam ring, this was not generally accepted until an X-ray crystallographic determination of the structure had been completed.

RCONH )=r)< o '" (I) 'C0 H 2 Penicillin was the first naturally occurring antibiotic to be characterised and used in clinical medicine.

It is now seen as the progenitor of the tJ-Iactam family of antibiotics, which are characterised by the possession of the four- membered tJ-Iactam ring.

Chapters in this book will describe how current research has demonstrated that other lactam structures may also show antibacterial activity.

Penicillins and cephalosporins (2), the second member of the tJ-Iactam antibiotic family, were both originally discovered in fungi but later detected in streptomycetes.

Until 1970 penicillins and cephalosporins were the only examples of naturally occurring tJ-Iactam antibiotics.

The discovery of 7-a-methoxy- cephalosporins (3) from Streptomyces in 1971 stimulated the search for novel tJ-Iactam antibiotics from microbes, both by using sensitive new screening procedures, and by laboratory synthesis.