Synthesis and Biological Activity of Silicon-Containing Ethylsulfonylpyridine Insecticides.

Ethylsulfonylpyridines are a novel chemical class of insecticides with excellent broad-spectrum activity and an unprecedented mode of action. With the objective of discovering novel ethylsulfonylpyridines with a broader spectrum, wider range of uses, and/or improved properties, we have started a research program aimed at introducing silicon motifs and studying their biological effects. We designed a series of Oxazosulfyl analogues where the hydrogen atom at the 5-position of the pyridyl moiety is replaced by a trialkylsilyl group and prepared these compounds applying denovo synthetic methodology. Our novel ethylsulfonylpyridines exhibit excellent insecticidal activities. The best compound, A18, resulting from our research exhibited an LC50 value of 0.30 mg/L against Plutella xylostella and reached the activity level of the commercial standard Oxazosulfyl. Our findings confirmed our working hypothesis that at the 5-position of the pyridyl moiety larger groups with different hydrophobic, electronic, and steric properties are tolerated.

Design, Synthesis, and Properties of Silicon-Containing meta-Diamide Insecticides.

Silicon-containing compounds are sporadically used in crop protection and drug discovery and have demonstrated to increase the biological efficacy as well as to reduce toxicity, improve physicochemical properties, and favorably impact the environmental profile. As part of our research, we have investigated the application of bioisosteric silicon replacements in meta-diamide insecticides and studied the biological activity and molecular properties of the corresponding novel compounds. At all meaningful structural elements of the meta-diamides, silicon-containing substituents were introduced and synthetic methodology was developed for their syntheses. As the most promising compound, silicon-containing meta-diamide II-18 emerged, which exhibits a very low LC50 value of 2.00 mg/L against Mythimna separata and compares well to the reference compounds 28 (LC50 = 0.17 mg/L) and II-20 (LC50 = 0.27 mg/L). Our research on silicon-containing crop protection compounds once again confirmed that the biological activity can be beneficially affected by the insertion of silicone substituents and that the introduction of well-chosen silicone motifs is an excellent strategy for agrochemical research.

Silicon-Containing Complex II Acaricides─Design, Synthesis, and Pharmacological Optimization.

Bioisosteric replacement has been proven to be a powerful strategy in life science research. In this review, general aspects of carbon-silicon bioisosteric substitution and its applications in pharmaceutical and crop protection research are described. Carbon and their silicon analogues possess similar intrinsic properties. Replacing carbon with silicon in pharmaceuticals and pesticides has shown to result in positive effects on efficacy and selectivity, physicochemical properties, and bioavailability and also to eliminate or improve human or environmental safety properties as well as to provide novelty and new intellectual property in many cases. Furthermore, the application of carbon-silicon substitution in the search for new complex II acaricides is highlighted. This research led to the discovery of sila-cyflumetofen 23a and other silicon-containing analogues of cyflumetofen that match or exceed the acaricidal activity of cyflumetofen. The molecular design strategy, synthetic aspects, biological activity, computational modeling work, and structure-activity relationships will be discussed.