Sterol biosynthesis inhibitors fungicidal

Kato, T. (1986). Sterol biosynthesis in fungi A target for broad spectrum fungicides. In Chemistry of Plant Protection No. 1 Sterol Biosynthesis Inhibitors and Anti-feeding Compounds. Berlin Springer-Verlag, 1-24. 

Well over 100 plant pathogens have become resistant to various fungicides under field conditions. Failure of the acyl alanines, benzimidazoles, thiophanates, carboxanilides, dicarboximides, hydroxypyrimidines, some organophosphates, and most of the antibiotics has occurred. In other cases, a moderate decrease in sensitivity without a rapid loss of disease control has been observed as in the case of sterol biosynthesis inhibitors (triazoles, pyrimidines, and imidazoles) and organophosphates. The most effective approach is to use fungicides having different modes of action in combination,... 

Sterol biosynthesis inhibiting insecticides. The earliest examples of sterol biosynthesis inhibitors were triadimefon, imazalil, and triarimol. These compounds act by blocking the C14 alpha demethylation step in ergosterol biosynthesis [54], Further work in this area has resulted in numerous fungicides, a number of them containing aromatic fluorine, perfluoroalkyl ethers, and the trifluoromethylphenyl group (Fig. 11). In this section, we will discuss the trifluoromethylphenyl sterol biosynthesis inhibitors, such as triflumizole and fluotrimazole. 

In addition to the trifluoromethylphenyl sterol biosynthesis inhibitors discussed in Section 2.1.1.3, a number of fluorine phenyl-containing azoles were introduced in the years 1984 through 1993. Though these molecules share some common structural features, such as the triazole heterocycle and a 4-fluorophenyl ring in at least three of the four fungicides shown below, each also has unique chemical features. For instance, in the case of flusilazole (Punch , Nustar , Triumph , Olymp ) [164], a silicon atom is present. This represented that first time silicon... 

It was not until the late 1960s that effective systemic fungicides appeared on the market, and their development represents an important breakthrough in the field of plant chemotherapy. The major classes of systemic fungicides developed since 1966 are oxathiins, benzimidazoles, thiophanates, and pyrimidines. Other effective systemic fungicides used currently include antibiotics, morpholines, organophosphorus compounds, and most recently, the sterol biosynthesis inhibitors, e.g., triazoles. 

Scheme 4.46 Different examples of fluorinated fungicides (top) sterol biosynthesis inhibitors and (bottom) a benzamide-based compound [15—22],...

G1 3 C14-DeMethylation Inhibitors in sterol biosynthesis (DMI fungicides) Piperazines, pyridines, pyrimidines, imidazoles, triazoles Prochloraz, propiconazole, tebuconazole, epoxiconazole, prothioconazole Broad spectrum over 30 commercial compotmds... 

Exploration of the area of imidazole-l-carboxamides has led to the discovery of prochloraz, a broad-spectrum fungicide for use on a variety of crops. Prochloraz and its analogues are inhibitors of ergosterol biosynthesis and structure-activity relationships in the area are discussed. In particular, the usefulness of an in vitro assay for sterol biosynthesis as a guide to the chemical effort is considered. Finally, the biological activity of prochloraz is briefly described. 

Inhibitors of sterol biosynthesis provide many, useful, broad spectrum, fungicides, and it is essential that their effectiveness is retained as long as possible. Of the two major groups of SBI fungicides, only.the morpholines, which inhibit A reductase and/or A -A isomerase depending on their... 

Many of the enzymes in the sterol biosynthesis pathway have selective-inhibitors (Fig. 3). These include some extremely important classes of drugs such as Statins , used to treat high cholesterol, bisphosphonates, used to treat osteoporosis, allylamines (e.g., terbinafine) and azoles used to treat fungal infections, and morpholines which are used as fungicidal agrochemicals. 

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. 

Fungicides that inhibit targets within the fungal sterol biosynthesis have been the most important group of specific fungicides world-wide for over two decades. The biochemical basis of this success is the fact that fungi have specific sterols that differ from those in plants and animals, giving the chance to develop selective inhibitors. 

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