The scientists of the Zelinsky Institute developed a scalable and technological method for the synthesis of a fundamentally new class of fungicides for plant protection

28 april 2022 г.

The development of new types of fungicides for agriculture and medicine is vital due to the increase in the resistance of pathogenic fungi to currently used compounds. Despite the wide range of commercial antifungal drugs being marketed, most of them belong to already known chemical classes with a common mechanism of action (for example, these are succininate dehydrogenase inhibitors, inhibitors of the complex III mitochondrial electron transport chain, demethylase inhibitors).

Scientists from the Laboratory for the Study of Homolytic Reactions of the ZIOC proposed 4-substituted-4-nitropyrazolin-5-ones (nitropyrazolones) as highly active fungicides of a new structural type. The researchers proposed a convenient, scalable and atom-economical method for the synthesis of nitropyrazolones. This approach is applicable to multigram synthesis and allows the production of a wide range of nitropyrazolones in high yields and purity, making them readily available products. The synthesized compounds showed high fungicidal activity against a wide range of phytopathogenic fungi (Venturia inaequalis, Rhizoctonia solani, Fusarium oxysporum, Fusarium moniliforme, Bipolaris sorokiniana, Sclerotinia sclerotiorum). Their inhibitory activity against mycelial growth was comparable or superior to that of the current commercial active ingredient, kresoxim-methyl. In vitro activity against Candida albicans and Aspergillus niger has shown that nitropyrazolones are also active against human pathogenic fungi. The key structural factors necessary for the manifestation of high fungicidal activity have been established: an aromatic substituent at the N1 atom and small substituents in the C3 and C4 positions of the pyrazolone ring.

Source:

Alexander S. Budnikov, Elena R. Lopat’eva, Igor B. Krylov, Oleg O. Segida, Andrey V. Lastovko, Alexey I. Ilovaisky, Gennady I. Nikishin, Alexey P. Glinushkin, Alexander O. Terent’ev 4-Nitropyrazolin-5-ones as Readily Available Fungicides of the Novel Structural Type for Crop Protection: Atom-Efficient Scalable Synthesis and Key Structural Features Responsible for Activity // J. Agric. Food Chem. 2022, 70, 15, 4572–4581. DOI: 10.1021/acs.jafc.1c07413.