It was the late Professor Kenji Mori, the giant of pheromone synthesis and pioneer of pheromone stereochemistry, who laid the foundation for the practical application of insect pheromones, which play an important role in Integrated Pest Management, one of the key concepts of agriculture in the 21st century. Therefore, it would be meaningful to retrace his achievements at this time, three and a half years after his death. In this review, we would like to introduce some of his notable synthetic studies from his Pheromone Synthesis Series and reconfirm his contributions to the development of pheromone chemistry and their impacts on natural science.

We investigated the synthesis and herbicidal activity of optically active cinmethylin, its enantiomer, and C3-substituted cinmethylin analogs. Optically active cinmethylin could be obtained in seven steps with the Sharpless asymmetric dihydroxylation of α-terpinene. The synthesized cinmethylin and its enantiomer showed similar herbicidal activity, which was independent of the stereochemistry. Next, we synthesized cinmethylin analogs with various substituents at the C3 position. We found that analogs with methylene, oxime, ketone, or methyl groups at the C3 position show excellent herbicidal activity.

The species selectivity of class 2 dihydroorotate dehydrogenase (DHODH), a target enzyme for quinofumelin, was examined. The Homo sapiens DHODH (HsDHODH) assay system was developed to compare the selectivity of quinofumelin for fungi with that for mammals. The IC₅₀ values of quinofumelin for Pyricularia oryzae DHODH (PoDHODH) and HsDHODH were 2.8 nM and >100 µM, respectively. Quinofumelin was highly selective for fungal over human DHODH. Additionally, we constructed recombinant P. oryzae mutants where PoDHODH (PoPYR4) or HsDHODH was inserted into the PoPYR4 disruption mutant. At quinofumelin concentration of 0.01–1 ppm, the PoPYR4 insertion mutants could not grow, but the HsDHODH gene-insertion mutants thrived. This indicates that HsDHODH is a substitute for PoDHODH, and quinofumelin could not inhibit HsDHODH as in the HsDHODH enzyme assay. Comparing the amino acid sequences of human and fungal DHODHs indicates that the significant difference at the ubiquinone-binding site contributes to the species selectivity of quinofumelin.

Developed by Mitsui Chemicals Agro, Inc. (Tokyo, Japan), quinofumelin is a novel fungicide with a distinct chemical structure including 3-(isoquinolin-1-yl) quinoline, demonstrating fungicidal activity against a variety of fungi, including rice blast and gray mold. We screened our compound library to identify curative compounds for rice blast and evaluated the effect of fungicide-resistant strains of gray mold. Our research demonstrated that quinofumelin has curative effects against rice blast and is not cross-resistant to existing fungicides. Accordingly, the use of quinofumelin can be considered a novel approach for disease control in agricultural production. In this report, the discovery of quinofumelin from the initial compound is described in detail.