Fungicide development

Figure 11. First azole antimycotics and fungicides developed for practical use. (Reproduced with permission from Ref. 9. Copyright 1983 Pergamon Press.)...

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. 

Dithiocarbamates were the next step of fungicide development. They are organic compounds containing several sulfur atoms and have a similar mode of action as sulfur. Often, they also contain other inorganic... 

Bupirimate (75) is the N,N-dimethylsulfamoyl ester of the systemic fungicide ethirimol both are members of the hydroxypyrimidine group of fungicides developed specifically to combat powdery mildew diseases. They may owe their activity to interference with purine metabolism in the fungus. 

Having identified hexaconazole as a fungicide development compound it was important to synthesise any closely related compounds that may also possess good fungicidal activity. In particular, we have investigated the importance of the hydroxyl group and the nature of the normal butyl side chain in the molecule on the biological activity. 

Resistance to insecticides was recorded as a problem just a few years after the introduction of the newer persistent insecticides, whereas resistance to herbicides and fungicides developed much later. Figure 9.1 shows an approximate graph of the development of resistance. 

Molecular Design and Target Site Analysis in Fungicide Development... 

Most fungicides developed for plant disease control before 1965 are multisite biochemical inhibitors that lack the chemical properties and biological specificity required for internal therapeutic action in higher plants. This group of plant protectants include such compounds as the Inorganic copper fungicides, captan, chlorothalonil, dithiocarbamates and chlorinated quinones. 

As conditions require, the above sequence of processing can be stopped at any step. Take Di-ku-Shuang (DKS) (see Table I) for example. It is a new fungicide developed in the early iventies by Sichuan Pesticide Research Institution. It has. .a excellent systemic effect on bacterial leaf blight of rice, which is ranked as one of the major crop diseases in China. 

Fenpiclonil (1) was the first phenylpyrrole fungicide developed by Ciba-Geigy for seed treatment [14]. Two years later fludioxonil (2) was developed as a foliar fungicide [15] and for seed treatment [16]. 

Fig. 16.2.1. Representative rice sheath blight control fungicides developed in japan since 1980.

The reaction of potassium phthalimide with trichloromethanesulfenyl chloride yields folpet (N-trichloromethylthiophthalimide), a fungicide developed by Chevron, which has a world production of some 6,000 tpa. Future production, however, will probably decline, because of local bans (e.g. West Germany 1986). 

Powdery mildew is one component of this disease matrix which has always challenged fungicide development. Strains of this pervasive disease have developed resistance to most commercial products while the standards of mildew control have steadily increased (1). Presently there exists a need for more persistent compounds possessing novel modes of action as well as systemic activity in the host crop for the control of these infections (1,2). 

The preparation of fluoroaromatics by the reaction of KF with perhaloaromatics, primarily hexachloroben2ene, has received considerable attention. Two methods were developed and include either the use of an aprotic, polar solvent, such as /V-methy1pyrro1idinone (8), or no solvent (9). These methods plus findings that various fluoroaryl derivatives are effective fungicides (10) prompted development of a commercial process for the production of polyfluoroben2enes (11). The process uses a mixture of sodium and potassium fluorides or potassium fluoride alone in aprotic, polar solvents such as dimethyl sulfoxide or sulfolane. 

PERFLUOROALKYLPYRIDINES New developments ia trifiuoromethylpyridine technology are associated with the commercialization of numerous crop-protection chemicals as herbicides, fungicides, and iasecticides (Table 15). Physical properties for representative trifiuoromethylpyridines are fisted ia Table 13. 

Mercury. The fkst successful use of mercury as a fungicide occurred in 1913 (8). The fkst seed treatment compound developed was chloro(2-hydroxyphenyl)mercury [90-03-9] (1). Subsequentiy, a number of organic mercury derivatives having general formula RHgX have been used. 

Amorolfine [78613-35-17 is a molecule that is totally different from this group it is a morpholine derivative (15) (19). This substance has a broad-spectmm activity and has a fungicide effect at fairly low concentrations. The development of a nail varnish for treatment of onychomycoses could be very interesting. 

Fungicides. Formalin as Paracide-F is the only registered fungicide and is labeled for use on eggs of trout, salmon, and esocids at 1,000 —2,000 mg/L for 15 min (9—11). DeHvery apparatus has been developed to reduce human exposure to formalin. Fish culturists in the Pacific Northwest have... 

Mancozeb is a dithiocarbamate pesticide with a very low solubility in organic and inorganic solvent. In this work we have developed a solvent free, accurate and fast photoacoustic FTIR-based methodology for Mancozeb determination in commercial fungicides. The proposed procedure was based on the direct measurement of the solid samples in the middle infrared region using a photoacoustic detector. A multivariate calibration approach based on the use of partial least squares (PLS) was employed to determine the pesticide content in commercially available formulations. 

Daikon and wasabi phytoalexins are weak fungicidal alkaloids having a stabilized 1-methoxyindole structure. Relying on the expectation that more potent substances can be found among their derivatives, synthetic studies are in progress according to the method developed in Scheme 22 in Section IV.G. 

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