Industrial Synthesis of Semisynthetic Antibiotics

Even in the early days of investigations on penicillin synthesis by direct fermentation, the importance of incorporating different side chains for antibiotic activity was evident. Addition of various mono-substituted acetic acids to the Penicillium fermentation medium gave the corresponding new penicillins with varying activity profiles. Notably, such studies led to phenoxymethyl penicillin (Pen V), which is acid stable and orally active. Up to the late 50′s, only two of the many penicillins produced by fermentation, namely Pen G and Pen V, proved to be clinically useful, though indeed these have stood the test of time. Further progress here was limited, as a result of the selective biochemical incorporation of side-chains by the Penicillium fungus (restricted mainly to aliphatic or aryl aliphatic carboxylic acids).