Selective reminiscences of beta-lactam antibiotics: early research on penicillin and cephalosporins.
The discovery, made in Oxford, that crude penicillin could cure systemic and life-threatening bacterial infections was followed by attempts to purify penicillin, to determine its structure and then to produce it by total chemical synthesis. The beta-lactam structure of the molecule, first proposed in October 1943, was a source of controversy until 1945. However, no useful chemical synthesis was achieved and fermentation became the commercial source of the antibiotic. In 1953, one of the products of a Cephalosporium sp. from Sardinia was shown to be a new and hydrophilic penicillin (penicillin N). This was contaminated with a substance having the same side-chain but a characteristic absorption spectrum. The latter, cephalosporin C, showed antibacterial activity but was not inactivated by a penicillinase. The determination of its beta-lactam structure and isolation of its nucleus enabled pharmaceutical companies to produce many semisynthetic cephalosporins. A new tripeptide was later found to be an intermediate in the biosynthesis of both penicillin N and cephalosporin C, and this was followed by the complete elucidation of the biosynthetic pathways leading to these compounds and to benzylpenicillin.
Abraham
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Sir William Dunn School of Pathology, University of Oxford.
D002511:Cephalosporins / Q000737:chemistry / Q000266:history*; D004739:England; D049673:History, 20th Century; D010406:Penicillins / Q000737:chemistry / Q000266:history*
D002511:Cephalosporins; D010406:Penicillins