Fungicides, inhibiting ergosterol biosynthesis

Synthesis-Directing Structure-Activity Relationships of Some Fungicides Inhibiting Ergosterol Biosynthesis... 

Although termed "SI" or "EBI" compounds, the latter referring to ergosterol biosythesis inhibitors, these compounds do not all inhibit ergosterol biosynthesis at the same metabolic site (Fig. 2). For instance, the fungicide tridemorph, unlike most EBI compounds, does not inhibit demethylation at C-14 but rather it apparently prevents the A A isomerization resulting in the accumulation of A containing sterols in treated cells (3). 

Schepers, H. T. A. M. 1983. Decreased sensitivity of Sphaero-theca fuliginea to fungicides which inhibit ergosterol biosynthesis. Neth. J. PI. Path. 89 185-187. 

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. 

These 1,2,4-triazole fungicides share a common mode of action by inhibiting the C-14a-demethylation step in ergosterol biosynthesis (Figure 1) ( 3 ) between 24-methylenedihydrolanosterol and 4,4-dimethylergosta-8,14,24(28)-trienol. 

The fust strongly active, broad spectrum, ergosterol biosynthesis inhibiting fungicide we prepared was 2-(2,4-dichlorophenyl)-l-(l-imidazolyl) hexane, 1, and we began a synthesis program in this area of chemistry in an attempt to obtain an... 

Many fungicides [15] act by inhibiting sterol biosynthesis. More specifically, they block the C-14a demethylation step in ergosterol biosynthesis [16]. In many of these compounds (Flutriafol [17], Flusilazole [18], Triflumizole [19], Fluotri-... 

Naftifine is representative of the allylamine drugs that inhibit squalene-2,3-epoxidase and thus inhibit ergosterol biosynthesis. The drug has broad-spectrum fungicidal activity. Naftifine... 

Semisynthetic y0-lactam antibiotics with a 1,2,4-triazolyl substituent have been prepared and are in clinical use. However, the most important application of 1,2,4-triazoles is as biocides. 3-Amino-1,2,4-triazole (amitrole, amizol) is an unselective herbicide. Triadimenol 4 is one of the most effective fungicides. Its configuration IS, 2R) is essential for its action [162]. The 1,2,4-triazole fungicides inhibit the biosynthesis of ergosterol in fungi. 

Ergosterol synthesis is inhibited differently by another class of fungicides, namely by preventing demethylation at C-14 during biosynthesis. As a result, useless sterols accumulate such as 14-methylfecosterol. Examples of this class are fenarimol 6.64), which is l-(2,4 -dichlorodiphenyl)-l-pyrimidin-5-yl-methanol, and triadimefon 6.65) which is l-(4-chlorophenoxy-3,3-dimethyl-l-(l,2,4-triazol-l-yl)butan-2-one. These are somewhat wedge-shaped molecules with alternating lipophilic and hydrophilic areas. The heterocyclic fragment can be varied to be pyridine, piperazine, or imidazole as in buthiobate, triforine, or imazilil, respectively (Kato, 1983). 

In oilseed rape the rate of infection with different fungi was reduced by treatments with triapenthenol and BAS 111.. W [7, 32, 46]. Paclobutrazol and ancymidol improved the resistance of melon seedlings to fusarium wilt [9]. The effects observed are thought to be mostly due to direct fungicidal effects via inhibition of fungal ergosterol biosynthesis [17]. Evidence is, however, also available that other effects such as delayed senescence have led to increased resistance of the plants [32]. 

Triazoles have been applied as biocides. 3-Amino-l,2,4-triazole (amitrole, ami-zole) is an unselective herbicide. Triadimenol (28) is a very effective fungicide, its absolute configuration 1S,2J is essential for its activity [518]. The fungicides of the 1,2,3-triazole type inhibit ergosterol biosynthesis in fungi. 

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