Strobilurins commercial fungicides

P-Methoxyacrylates. This is an important class of commercial fungicides based on a group of natural products, the strobilurins (see Fig. 10), such as strobilurin A and oudemansin A. Strobilurins act by inhibition of mitochondrial respiration. In 1996, the first representatives of this class of fungicide were launched, including azoxystrobin [52], In 1999, the first fluorine-containing strobilurin, trifloxystrobin (Flint ) [53], was launched by Syngenta and later acquired by Bayer for 760 million. 

The extremely broad activity spectrum of strobilurins, with potential to control all four major classes of phytopathogenic fungi (Ascomycetes, Basidiomycetes, Deuteromycetes and Oomycetes), is unique among commercial fungicides. 

At present, nine different strobilurins have been introduced into the fungicide market (see Table 13.2.1 and Fig. 13.2.2 below), and one more has been announced as being developed in China (enestroburin). There is also a strobilurin commercialized in Japan as an acaricide (fiuacrypyrim). 

For this validation six commercial fungicides were selected three strobilurins and three azoles. The fungicides were selected because their metabolism in whole plants is documented, and although they cover only 2 classes of fimgicides they do vary in their physical/chemical properties, the rates of metabolism and the metabolites which are formed. The compounds tested are listed below. 

The strobilurins are an important new class of agricultural fungicides. The best examples exhibit an extremely useful spectrum of activity against many plant diseases of commercial importance. The first two products of this class, azoxystrobin and kresoxim-methyl, first sold just three years ago in April 1996, have already made a major impact on the global fungicide market. The importance of the strobilurins will increase in die years ahead as the established products are registered for use on further crops and in further territories, and as new products, currently under development, are launched. 

Figure 4 The commercial synthetic agricultural fungicides azoxystrobin and kresoxim-methyl, inspired by the natural strobilurins, such as strobilurin A and oudemansin A...

Many fungicides are being isolated from a variety of natural sources. Some of them may be useful as such. More often, variations on their structure are made to enhance activity reduce toxicity to the crop plant increase their stability to hydrolysis, light, enzymes and to make their chemical syntheses commercially attractive. Strobilurin (11.60) is such a case. It was isolated from a wood-rotting mushroom. This lead has resulted in a whole new class of fungicides, the (3-methoxyacrylates.269 A related compound is found in another mushroom. 

After more than 20 years of industrial research and development, strobilurins have become one of the most important classes of crop protection agents. With a distributor sales value of 1.3 billion US in 2004 [1], they currently represent approximately one-fifth of the world fungicide market (7.3 billion US in 2004 [1]). Within fungicides they rank - in commercial terms - second only to sterol biosynthesis demethylase inhibitors (DMI s), e.g. triazoles (see Chapter 17 of this book). This chapter also includes the three other Complec III inhibitors, famoxadone, fenamidone and cyazofamide, that, besides strobilurins, have achieved introduction in agricultural practice. 

Table 13.2.2 lists, for comparison, data for the commercialized strobilurin fungicides. The F values for mitochondrial target activity according to Eq. (1) were... 

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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