Semi-Synthetic Penicillins and the Growing Problem of Resistance

SEMI-SYNTHETIC PENICILLINS AND THE GROWING PROBLEM OF RESISTANCE 

The chemical structure of the penicillins remained in doubt throughout the war years despite considerable efforts and much speculation by a group led by Karl Folkers at Merck, and the Oxford group comprising Robert Robinson, Chain, Abraham and others. One of the major problems was that the initial microanalysis had not revealed the presence of a sulfur atom, and it was not until penicillamine was revealed in 1943 as the major acid degradation products of all the known penicillins that realistic structures could be 

Robert Robinson refused to accept the beta-lactam ring, suggesting that is the result when penicillin is in the solid form. You simply do not know what it is when the penicillin is in solution.  

The discovery that addition of side-chain precursors to the culture medium favoured production of the penicillin that had incorporated this side-chain allowed the production of a whole range of novel penicillins. Although around 100 such structures were prepared, only one had more desirable properties than penicillin G, and this was christened penicillin V or phe-noxymethylpenicillin. Although this compound was not as potent as penicillin G, it was much more stable to acid (in the stomach), and so could be administered by mouth rather than requiring injection like penicillin G. This was a major advantage for patients, and penicillin V rapidly became the antibiotic of choice for GPs. 

But just as the elimination of bacteria-induced infections seemed a realistic possibility, the bacteria retaliated against these new drugs. We should 

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