Insecticidal strobilurins

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]. 

Complex III has been very successfully exploited as a target site for fungicides such as the strobilurins, fanoxadone and fenamidone [75]. However, it has only been in the last few years that insecticidal or acaricidal products have used inhibition at Complex III as a mode of action. 

Several of the top 20 pharmaceuticals in gross sales in 1992 were natural products or close derivatives thereof (eg. Mevacor, Ceclor). Of the top 20 crop chemicals in this same period, only one class of compounds, the pyrethroids, are based on a natural substance, the plant metabolite pyrethrin. Three active areas of chemistry have the potential to impact this situation within the next ten years the methoxyacrylate family of fungicides based upon the fungal metabolite, strobilurin Basta, a post-emergent broad-spectrum herbicide based upon the Streptomyces viridochromogenes metabolite phosphinothricylalanylalanine and avermectin, and its semi-synthetic derivatives, insecticides originating from Streptomyces avermitilis. 

Five standard approaches to the generation of new areas for agrochemical (and pharmaceutical) research are commonly cited random screening speculative nthesis imitative ("me-too") chemistry biorational design and finally the exploitation of natural products (7). Although this last approach has found much commercial success in the development of novel insecticides (for example the pyrethroids), there are still relatively few examples of herbicides and fungicides which have been discovered in this way. This account describes the development of a new class of fungicides derived from the strobilurin family of natural products and related compounds, all of which are derivatives of P-methoxyacrylic acid. 

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