Strobilurins optimization

During the evolutionary process of lead-structure optimization, probably well over 50 000 strobilurin analogues were synthesized by competing industrial fungicide discovery research groups worldwide. Several compound types, and even specific compounds, were made independently at almost the same time. 

In the patent literature, many claims and some data can be found about insecticidal and acaricidal activities of strobilurins. Attempts to optimize insecticidal performance did not lead to a commercial product. It seems that, with strobilurins, sufficient insecticidal activity can only be obtained if the compound has very high lipophilicity and very high metabolic stability. This combination of properties gave numerous compounds with excellent insecticidal activity but also with unacceptably high acute mammalian toxicity, so that candidates were abandoned rather early in the research phase. It seems impossible to separate the tight connection between insecticidal and mammalian toxicity in this particular case. Similar problems have been reported for respiration inhibitors of Complex I [82a]. 

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