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      The continuing significance of chiral agrochemicals

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          Abstract

          Chemical crop protection is one of the most cost‐effective methods for agriculture, as crop failures can be prevented, and sustainable growth can be enabled regardless of the seasons. Agricultural production must be significantly increased in the future to meet the food needs of a growing world population. However, the continued loss of established active ingredients due to consumer perceptions, changing needs of farmers and ever‐changing regulatory requirements is higher than annually new active ingredients introduced to the market. The development of innovative active ingredients is therefore essential to continuously improve the selectivity, efficacy and favorable environmental profile of agrochemicals. Molecules with stereogenic centers can be considered here, as they often have different properties than non‐chiral molecules. Natural products and their congeners are still a valuable source of inspiration for chiral agrochemicals. However, only a few novel chiral agrochemicals are currently produced on an industrial scale as pure stereoisomers or in enriched form. As of 2018, around 43% of the 35 chiral products introduced to the market (herbicides, fungicides, insecticides, acaricides, and nematicides) contain one or more stereogenic centers in the molecule, and almost 69% of them have been marketed as racemic mixtures of enantiomers or stereoisomers. Surprisingly, the proportion of chiral agrochemicals is in the same order of magnitude as in the time frame from 2007 to 2017 with around 42%, respectively. This report therefore provides an overview of the continued importance of chiral agrochemicals brought to market in the last 6 years and describes the inherent related challenges of modern agrochemicals through the management of key aspects arising from innovative crop protection products. © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

          Abstract

          In the time frame 2018–2023, around 43% of the 35 chiral agrochemicals introduced to the market (herbicides, fungicides, insecticides, acaricides, and nematicides) contain one or more stereogenic centers in the molecule, and almost 69% of them have been marketed as racemic mixtures of enantiomers or stereoisomers.

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          Most cited references127

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          Function-oriented synthesis, step economy, and drug design.

          This Account provides an overview and examples of function-oriented synthesis (FOS) and its increasingly important role in producing therapeutic leads that can be made in a step-economical fashion. Biologically active natural product leads often suffer from several deficiencies. Many are scarce or difficult to obtain from natural sources. Often, they are highly complex molecules and thus not amenable to a practical synthesis that would impact supply. Most are not optimally suitable for human therapeutic use. The central principle of FOS is that the function of a biologically active lead structure can be recapitulated, tuned, or greatly enhanced with simpler scaffolds designed for ease of synthesis and also synthetic innovation. This approach can provide practical access to new (designed) structures with novel activities while at the same time allowing for synthetic innovation by target design. This FOS approach has been applied to a number of therapeutically important natural product leads. For example, bryostatin is a unique natural product anticancer lead that restores apoptosis in cancer cells, reverses multidrug resistance, and bolsters the immune system. Remarkably, it also improves cognition and memory in animals. We have designed and synthesized simplified analogs of bryostatin that can be made in a practical fashion (pilot scale) and are superior to bryostatin in numerous assays including growth inhibition in a variety of human cancer cell lines and in animal models. Laulimalide is another exciting anticancer lead that stabilizes microtubules, like paclitaxel, but unlike paclitaxel, it is effective against multidrug-resistant cell lines. Laulimalide suffers from availability and stability problems, issues that have been addressed using FOS through the design and synthesis of stable and efficacious laulimalide analogs. Another FOS program has been directed at the design and synthesis of drug delivery systems for enabling or enhancing the uptake of drugs or drug candidates into cells and tissue. We have generated improved transporters that can deliver agents in a superior fashion compared with naturally occurring cell-penetrating peptides and that can be synthesized in a practical and step-economical fashion. The use of FOS has allowed for the translation of exciting, biologically active natural product leads into simplified analogs with superior function. This approach enables the development of synthetically innovative strategies while targeting therapeutically novel structures.
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            Endoplasmic Reticulum-Plasma Membrane Contact Sites.

            The endoplasmic reticulum (ER) has a broad localization throughout the cell and forms direct physical contacts with all other classes of membranous organelles, including the plasma membrane (PM). A number of protein tethers that mediate these contacts have been identified, and study of these protein tethers has revealed a multiplicity of roles in cell physiology, including regulation of intracellular Ca2+ dynamics and signaling as well as control of lipid traffic and homeostasis. In this review, we discuss the cross talk between the ER and the PM mediated by direct contacts. We review factors that tether the two membranes, their properties, and their dynamics in response to the functional state of the cell. We focus in particular on the role of ER-PM contacts in nonvesicular lipid transport between the two bilayers mediated by lipid transfer proteins.
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              Pyrimidine and purine biosynthesis and degradation in plants.

              Nucleotide metabolism operates in all living organisms, embodies an evolutionarily ancient and indispensable complex of metabolic pathways and is of utmost importance for plant metabolism and development. In plants, nucleotides can be synthesized de novo from 5-phosphoribosyl-1-pyrophosphate and simple molecules (e.g., CO(2), amino acids, and tetrahydrofolate), or be derived from preformed nucleosides and nucleobases via salvage reactions. Nucleotides are degraded to simple metabolites, and this process permits the recycling of phosphate, nitrogen, and carbon into central metabolic pools. Despite extensive biochemical knowledge about purine and pyrimidine metabolism, comprehensive studies of the regulation of this metabolism in plants are only starting to emerge. Here we review progress in molecular aspects and recent studies on the regulation and manipulation of nucleotide metabolism in plants.
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                Author and article information

                Contributors
                p.jeschke@hhu.de
                Journal
                Pest Manag Sci
                Pest Manag Sci
                10.1002/(ISSN)1526-4998
                PS
                Pest Management Science
                John Wiley & Sons, Ltd. (Chichester, UK )
                1526-498X
                1526-4998
                17 January 2025
                April 2025
                : 81
                : 4 ( doiID: 10.1002/ps.v81.4 )
                : 1697-1716
                Affiliations
                [ 1 ] Heinrich‐Heine‐University Düsseldorf Institute of Organic Chemistry and Macromolecular Chemistry Duesseldorf Germany
                Author notes
                [*] [* ] Correspondence to: P Jeschke, Heinrich‐Heine‐University Düsseldorf, Institute of Organic Chemistry and Macromolecular Chemistry, University Street 1, D‐40225 Duesseldorf, Germany. E‐mail: p.jeschke@ 123456hhu.de

                Author information
                https://orcid.org/0000-0002-6369-093X
                Article
                PS8655
                10.1002/ps.8655
                11906909
                39821341
                ad779b0b-fdfd-4ebc-aabd-0f7e998cd59d
                © 2025 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 28 December 2024
                : 09 November 2024
                : 31 December 2024
                Page count
                Figures: 14, Tables: 4, Pages: 20, Words: 15000
                Funding
                Funded by: Ulrike Schmitz
                Categories
                Review
                Review
                Custom metadata
                2.0
                April 2025
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.5.4 mode:remove_FC converted:14.03.2025

                Pests, Diseases & Weeds
                chiral agrochemicals,structure–activity relationship,herbicides,fungicides,insecticides,acaricides,nematicides,mode of action,physicochemistry,selectivity,resistance

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