Development of a New Fungicide, Procymidone

Abstract

Procymidone [N-(3, 5-dichlorophenyl)-1, 2-dimethylcyclopropane-1, 2-dicarboximide] is a new type of fungicide highly effective against Botrytis and Sclerotinia diseases on various crops. The antifungal activity of the leading compound, H-5009 [1-cyanoethyl-N-(3, 5-dichlorophenyl) carbamate] was found in 1966, and various derivatives were prepared to investigate the structure-activity relationships. As the results, 3, 5-dihalo substituents on the benzene ring and cyclic imide moiety turned out to be essential to high activity. The effect of the substituents on benzen and imide rings was analyzed by using Hansch-Fujita method to derive the following conclusion. The larger hydrophobicity of m-substituents on benzen ring and the substituents on imide ring, and the stronger electron withdrawal and the smaller steric dimension of the benzene ring substituents, contribute to the-higher activity. Among the derivatives, procymidone has been selected and successfully developed as an agricultural fungicide for its high efficacy, low toxicity to non-target organisms, low impact to the environment. Procymidone was effective to control the diseases curatively as well as protectively. The fungicide exhibited residual activity on plant grown in a greenhouse and its activity persisted against rain. In addition, systemic activity was observed in plants. These properties result in good performance of procymidone in field. Hyphal tip growth of B. cinerea stopped immediately after the treatment of procymidone. Then hyphal cells swelled and finally bursted. Conidia also bursted, but hyphal protoplasts did not burst in the presence of procymidone and regenerated chains of yeast-like cells without any development of normal hypha. Wall-less mutant of Neurospora crassa was also less sensitive to procymidone than the wild strains. Effects of procymidone on respiration and synthetic metabolism of proteins, nucleic acids and lipids were examined by using the mycelia of B. cinerea, but remarkable inhibition was not observed. It is supposed that procymidone may act on cytoplasmic membrane and its action would be related to membrane function for cell wall synthesis.