Development Of Agrochemicals Research Articles

Synthesis of 15N-Pyridines and Higher Mass Isotopologs via Zincke Imine Intermediates.

Methods to incorporate stable radioisotopes are integral to pharmaceutical and agrochemical development. However, despite the prevalence of pyridines in candidate compounds, methods to incorporate 15N atoms within their structures are limited. Here, we present a general approach to pyridine 15N-labeling that proceeds via ring-opening to NTf-Zincke imines and then ring-closure with commercially available 15NH4Cl salts. This process functions on a range of substituted pyridines, from simple building block-type compounds to late-stage labeling of complex pharmaceuticals, and 15N-incorporation is >95% in most cases. The reactivity of the Zincke imine intermediates also enables deuteration of the pyridine C3- and C5-positions, resulting in higher mass isotopologs required for LCMS analysis of biological fluids during drug development.

Recent developments in fluorine-containing pesticides.

To ensure ongoing sustainability, the modern agrochemical industry is faced with enormous challenges. These arise from provision of high-quality food to increasing water use and environmental impact as well as a growing world population. The loss of previous agrochemicals due to consumer perception, changing grower needs and ever-changing regulatory requirements is higher than the number of active ingredients that are being introduced into the crop protection market. Therefore, the development of novel agrochemicals is essential to provide improved efficacy and environmental profiles. In this context, the introduction of fluorine atoms and fluorine-containing motifs into a molecule is an important method to influence its physicochemical properties. These include, for example, small difluoro- and trifluoromethyl, or trifluoromethoxy groups at aryl or heterocyclic aryl moieties but also fragments like 2,2,2-trifluoroethoxycarbonyl, trifluoromethylsulfonyl, trifluoroacetyl, as well as the so far unusal rest like heptafluoro-iso-propyl. This review gives an overview of recent developments of fluorine-containing pesticides launched over the past 7 years and describes a selection of current fluorine-containing development candidates. © 2023 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.

Synthesis of New Fatty N-Acylamino Amides from 3,4-Dichloroaniline with Crop Protection Activity

A series of biologically active N-acylamino amides were synthesized from readily available amino acids and common fatty acids from oil seeds, including the pharmacophoric group in the family of herbicides propanil, linuron, and diuron. The esterification followed by N-acylation with long-chain fatty acids was carried out with O-(benzotriazole-1-yl)-N,N,N’,N’-tetramethyluronium tetrafluoroborate (TBTU) as activating agent. The N-acylamino esters were synthesized and isolated in good yields (70-98%), which after the hydrolysis step, provided the N-acylamino acids. Finally, new N-acylamino amides were obtained from the reaction with 3,4-dichloroaniline in the presence of TBTU and N,N-diisopropylethylamine (DIPEA), in yields between 24-83%. Bioassays were conducted against arthropod strawberry pests Chaetosiphon fragaefolii, Duponchelia fovealis, and Drosophila suzukii, without any registered compound for use in strawberry crops in Brazil. The bioassay studies showed promising results, with mortality percentages ranging from 20-80%, and the best relative mortality by N-oleyl glycinamide, suggesting a possible fatty chain-amino acid synergistic bioactivity. Overall, this study provides an efficient and sustainable method for synthesizing biologically active N-acylamino amides from abundant natural sources, with potential applications in the development of ecofriendly agrochemicals.

Visualizing active fungicide formulation mobility in tomato leaves with desorption electrospray ionisation mass spectrometry imaging.

Newer and safer agrochemicals are always in demand to meet the increasing needs of a growing population for affordable food. Spatial chemical monitoring of the active mobility of an agrochemical is essential to this agrochemical development process and mass spectrometry imaging (MSI) is proposed as a safer, easier alternative to the existing standard of autoradiography for the same. With desorption electrospray ionisation mass spectrometry imaging (DESI MSI) using leaf imprints, we were able to visualize the active agrochemical mobility of a commercial fungicide formulation with the active ingredient Azoxystrobin in whole tomato leaves. The leaf-imprinting method was optimized with precise control over the pressure conditions and time of imprinting to yield highly consistent samples for imaging. The reproducibility of this method was tested with the Azoxystrobin formulation applied to tomato leaves and was compared to the mobility of the unformulated Azoxystrobin standard in similar application conditions. The xylem mobility and the lateral-leaf lamina spreading of the fungicide were visualized with mass spectrometry imaging and validated using complementary LC-MS studies. The necessity and importance of the agrochemical application as a formulation were re-iterated by the limited mobility observed in Azoxystrobin standard studies compared to the Azoxystrobin formulation. This mass spectrometry imprint-imaging method could be translated for the visualization of any xenobiotic in further foliar systems particularly with soft leaves.

Genome mining reveals novel biosynthetic gene clusters in entomopathogenic bacteria

The discovery of novel bioactive compounds produced by microorganisms holds significant potential for the development of therapeutics and agrochemicals. In this study, we conducted genome mining to explore the biosynthetic potential of entomopathogenic bacteria belonging to the genera Xenorhabdus and Photorhabdus. By utilizing next-generation sequencing and bioinformatics tools, we identified novel biosynthetic gene clusters (BGCs) in the genomes of the bacteria, specifically plu00736 and plu00747. These clusters were identified as unidentified non-ribosomal peptide synthetase (NRPS) and unidentified type I polyketide synthase (T1PKS) clusters. These BGCs exhibited unique genetic architecture and encoded several putative enzymes and regulatory elements, suggesting its involvement in the synthesis of bioactive secondary metabolites. Furthermore, comparative genome analysis revealed that these BGCs were distinct from previously characterized gene clusters, indicating the potential for the production of novel compounds. Our findings highlighted the importance of genome mining as a powerful approach for the discovery of biosynthetic gene clusters and the identification of novel bioactive compounds. Further investigations involving expression studies and functional characterization of the identified BGCs will provide valuable insights into the biosynthesis and potential applications of these bioactive compounds.

Rhodium(III)-Catalyzed C–H Activation in Indole: A Comprehensive Report (2017–2022)

AbstractIn the realm of synthetic organic chemistry, the catalysis of directed C–H activation by transition metals is an outstanding and efficient method for the synthesis of natural products, organic materials, and fundamental organic building blocks. Notably, this strategy has experienced remarkable advances in recent years, particularly in its application to various substrate classes, including the essential indole scaffold. Indole is a highly sought-after target in organic chemistry. The significance of indole extends beyond its use in total synthesis and drug discovery. It also serves as an important tool in the development of pharmaceutical agents, agrochemicals, and materials. By targeting indole, synthetic chemists can access a wide range of bioactive compounds, which opens new avenues for drug development and chemical biology research. The synthesis of structurally varied indoles has been greatly aided by the development of a comprehensive toolkit made possible by the use of C–H activation as a versatile functionalization platform. This review highlights the latest breakthroughs in rhodium-catalyzed C–H activation at the C2, C4, and C7 positions of the indole scaffold. These developments represent significant progress in the field and hold promising potential for further advances in the synthesis of indole-based compounds.1 Introduction2 The Development of Rhodium-Catalyzed C–H Activation3 General Mechanistic Introduction to Rh(III)-Catalyzed C–H Activation4 Direct C–H Functionalization of Indoles4.1 C2 Activation of Indoles4.2 C4 Activation of Indoles4.3 Dual C–H Activation Strategy4.4 C7 Activation of Indoles5 Conclusion

Chemistry of Quinolines and their Agrochemical Potential

Abstract: Human population is increasing at an alarming rate which indirectly imposes pressure on agriculture and food supply. However, crop production is reduced by pathogenic infections which have engrossed the attention of chemists and agriculturists to develop newer agrochemicals with improved characteristics. Quinoline, one of the nitrogen-containing heterocyclic compound act as a privileged scaffold in the designing of highly efficient drugs due to their chemical and biological diversity. It has gained significant attention for several years due to its broad spectrum of biological activities such as anti-malarial, anti-microbial, anti-cancer, anti-inflammatory, anti-plasmodial, and anti-protozoal etc. The depiction of varied biological activities of quinoline impelled us to outlook the progress of synthesis and agrochemical potential of numerous quinoline derivatives with well-known and typical examples from 2015 to 2021. The review focuses on the advancement in the synthesis of quinoline derivatives and their agrochemical potential. This review revealed that abundant work has been done in order to synthesize quinoline derivatives and were evaluated for their agrochemical potential using different methods. The information given in this article may be helpful to the researchers to analyze the already reported studies and explore new compounds for the development of efficient agrochemicals.

On the Selectivity in the Synthesis of 3-Fluoropiperidines Using BF3-Activated Hypervalent Iodine Reagents.

Fluorinated piperidines find wide applications, most notably in the development of novel therapies and agrochemicals. Cyclization of alkenyl N-tosylamides promoted by BF3-activated aryliodine(III) carboxylates is an attractive strategy to construct 3-fluoropiperidines, but it suffers from selectivity issues arising from competitive oxoaminations and the inability to easily modulate the reactions diastereoselectivity. Herein, we report an itemized optimization of the reaction conditions carried out on both cyclic and acyclic substrates and outline the origins of substrate- and reagent-based stereo-, regio-, and chemoselectivity. Extensive mechanistic studies encompassing multinuclear NMR spectroscopy, deuterium labeling, rearrangements on stereodefined substrates, and careful structural analyses (NMR and X-ray) of the reaction products are performed. This revealed the processes and interactions crucial for achieving controlled preparation of 3-fluoropiperidines using I(III) chemistry and has provided an advanced understanding of the reaction mechanism. In brief, we propose that BF3-coordinated I(III) reagents attack C═C to produce the corresponding iodiranium(III) ion, which then undergoes diastereodetermining 5-exo-cyclization. Transiently formed pyrrolidines with an exocyclic σ-alkyl-I(III) moiety can further undergo aziridinium ion formation or reductive ligand coupling processes, which dictate not only the final product's ring size but also the chemoselectivity. Importantly, the selectivity of the reaction depends on the nature of the ligand bound to I(III) and the presence of electrolytes such as TBABF4. Reported findings will facilitate the usage of ArI(III)-dicarboxylates in the reliable construction of fluorinated azaheterocycles.

Prospects of plant-derived metallic nanopesticides against storage pests - A review

The desire to increase agricultural productivity and to alleviate food losses caused by insects during post-harvest storage periods has augmented the rampant use of unsafe chemo-synthetic pesticides. The elevated health risks on human or domestic animals and environmental pollution by chemo-pesticides have shifted the focus of getting eco-friendly pesticides from biological entities. Research on the nanotechnological application in agriculture has become popular and promising. The diversity among plant species as well as the possession of different insect-specific bioactive compounds makes them the favoured choice for exploring active ingredients, and the application of nanoscience has facilitated the development of effective nano-biopesticides. Varieties of phytochemical groups act as reducing- and stabilizing agents during the biosynthesis of metallic nanoparticles that would be operated as nanobiopesticides. Moreover, green synthesis of metallic nanoparticles or nano-conjugates, especially silver nanoparticles have been experimentally proven successful in controlling insects of stored food products. This review compiles phyto-derived metallic nanoparticles' potential and effectiveness against storage insects, and the analysis will augment research in designing and promoting the development of eco-friendly agrochemicals.

Recent Development of Versatile Polyphenol Platforms in Fertilizers and Pesticides.

The utilization of agrochemicals has been of significant importance in both the cultivation and disease control of crops. The development of advanced agrochemicals that are both effective and eco-friendly has been made possible through the use of slow delivery platforms and surface modification technology. Inspired by the nature of mussel adhesion, polyphenolic platforms with versatile properties have been extensively employed in various applications, including agro-food, owing to their ability to flexibly modulate chemical and surface characteristics. This mini-review highlights the development of polyphenols, such as polydopamine and tannic acid, in the field of agrochemicals, particularly in the design and production of novel fertilizers and pesticides. The synthetic approach, active ingredient release performance, foliar adhesion, and design of polyphenolic-based agrochemicals in recent years have been discussed to explore their potential applications and limitations. We believe that utilizing versatile polyphenolic materials and their characteristics for agro-food applications can provide innovative ideas and suggestions for developing novel agrochemicals suitable for modern and sustainable horticulture and agriculture.

Catalytic Difluoromethylation of Alkenes with Difluoroacetic Anhydride: Reactivity of Fluorinated Diacyl Peroxides and Radicals

AbstractGiven the importance of difluoromethylated molecules for drug and agrochemical development, much attention has been drawn to the establishment of related synthetic protocols, as exemplified by the CF2H radical‐mediated catalytic difluoromethylation of alkenes. However, most of these difluoromethylations proceed under photocatalytic conditions, whereas those requiring thermal conditions are few. Herein, we developed a general and practical method of Cu‐catalyzed alkene difluoromethylation with difluoroacetic anhydride (DFAA) as a CF2H source, showing that the thus realized amino‐, allylic‐, and oxy‐difluoromethylations involve bis(difluoroacetyl) peroxide (BDFAP) in situ generated from DFAA and H2O2 and further demonstrating the occurrence of carbo‐difluoromethylation under catalyst‐free conditions. The obtained results pave the way to the simple and efficient synthesis of a broad range of difluoromethylated species and thus facilitate their practical applications, including those in medicinal and agricultural chemistry. Moreover, we probed the mechanisms of the observed transformations, rationalized the extraordinary fast decomposition of BDFAP compared to that of diacyl peroxides containing CF3 or CF2Cl groups, and performed DFT calculations to shed light on the low stability and decomposition mode of BDFAP. Finally, we examined the influence of fluorinated radical philicity on the reaction outcome.

Carbene‐Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)−H Bonds

AbstractThe development of catalyst‐controlled methods for direct functionalization of two distinct C−H bonds represents an appealing approach for C−C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3)−H bonds employing readily available aldehyde as “acyl source” involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3)−H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho‐cyanoiodobenzene is essential in the oxidative radical N‐heterocyclic carbene catalysis to give a ketyl radical and C(sp3) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C−C formations in high efficiency under a metal‐ and light‐free catalytic conditions. Moreover, the prepared products show promising anti‐bacterial activities that shall encourage further investigations on novel agrochemical development.

Carbene-Catalyzed Intermolecular Dehydrogenative Coupling of Aldehydes with C(sp3)-H Bonds.

The development of catalyst-controlled methods for direct functionalization of two distinct C-H bonds represents an appealing approach for C-C formations in synthetic chemistry. Herein, we describe an organocatalytic approach for straightforward acylation of C(sp3)-H bonds employing readily available aldehyde as "acyl source" involving dehydrogenative coupling of aldehydes with ether, amine, or benzylic C(sp3)-H bonds. The developed method affords a broad range of ketones under mild conditions. Mechanistically, simple ortho-cyanoiodobenzene is essential in the oxidative radical N-heterocyclic carbene catalysis to give a ketyl radical and C(sp3) radical through a rarely explored intermolecular hydrogen atom transfer pathway, rendering the acylative C-C formations in high efficiency under a metal- and light-free catalytic conditions. Moreover, the prepared products show promising anti-bacterial activities that shall encourage further investigations on novel agrochemical development.

Novel Benzothiazole Derivatives as Potential Anti-Quorum Sensing Agents for Managing Plant Bacterial Diseases: Synthesis, Antibacterial Activity Assessment, and SAR Study

As quorum sensing (QS) regulates bacterial pathogenicity, antiquorum sensing agents have powerful application potential for controlling bacterial infections and overcoming pesticide/drug resistance. Identifying anti-QS agents thus represents a promising approach in agrochemical development. In this study, the anti-QS potency of 53 newly prepared benzothiazole derivatives containing an isopropanolamine moiety was analyzed, and structure-activity relationships were examined. Compound D3 exhibited the strongest antibacterial activity, with an in vitro EC50 of 1.54 μg mL-1 against Xanthomonas oryzae pv oryzae (Xoo). Compound D3 suppressed QS-regulated virulence factors (e.g., biofilm, extracellular polysaccharides, extracellular enzymes, and flagella) to inhibit bacterial infection. In vivo anti-Xoo assays indicated good control efficiency (curative activity, 47.8%; protective activity, 48.7%) at 200 μg mL-1. Greater control efficiency was achieved with addition of 0.1% organic silicone or orange peel essential oil. The remarkable anti-QS potency of these benzothiazole derivatives could facilitate further novel bactericidal compound development.

Gene-Directed Generation of Unprecedented Bioactive Compounds

Bioactive compounds with previously undescribed frameworks are highly desired for the discovery and development of new drugs and agrochemicals, but very few attempts have been reported to generate such molecules in biological contexts. Here, we present a gene-directed generation of architecturally unprecedented polyketide–indole hybrids (PIHs), which was conceptualized and materialized by employing polyketide synthases expressed in a heterologous vector, with simultaneous exposure to exogenous chemicals. To make an exemplification to this generally applicable approach, the ChrA and ChrB genes of Daldinia eschscholzii IFB-TL01 were integrated into the Aspergillus oryzae (AO) cell, and the resultant ChrA/ChrB-AO transformant was cultured in the indole-3-carbinol (I3C)-supplemented medium, leading to the production of seven skeletally undescribed PIHs named aochrabines A–G. Among them, aochrabines A–C exhibited a broad spectrum in inhibiting the growth of Gram-positive bacteria, whereas aochrabines B, C, and G showed moderate antitumor activities. Unexpectedly, the construction of such aochrabine molecules was achieved by the regioselective Michael addition of 3-methyleneindolium (3MI, generated from I3C in the AO culture) to different polyketide precursors with the yields (much) higher than those in the D. eschscholzii culture where comparable. Chemically, the benzyl-methine carbons in the precursor molecules were found to be made more vulnerable to the 3MI attack by the hydrogen-bonding between the ortho-hydroxyl and meta-carbonyl groups. Collectively, this is the first report of the ortho- and meta-substituent co-driven regioselective Michael addition of electrophilic methylene compounds to heterologous PKS production platform to in situ multiply the chemodiversity of microbial cultures, thus showing great potential in producing valuable compounds with new chemical space.

Regioselective C-H Trifluoromethylation and Its Related Reactions of (Hetero)aromatic Compounds.

Fluorinated functional groups, including trifluoromethyl group, play important roles in the development of drugs, agrochemicals, and organic functional materials. Therefore, the development of highly effective and practical reactions to introduce fluorinated functional groups into (hetero)aromatic compounds is highly desirable. We have achieved several regioselective C-H trifluoromethylation and related reactions by electrophilic and nucleophilic activation of six-membered heteroaromatic compounds and steric protection of aromatic compounds. These reactions proceed in good to excellent yields, even on a gram scale, with high functional group tolerance, and are applicable to the regioselective trifluoromethylation of drug molecules. In this personal account, the background of the introduction reactions of fluorinated functional groups, our reaction designs to achieve regioselective C-H trifluoromethylation and the related reactions of (hetero)aromatic compounds are explained.

A comprehensive DFT study on organosilicon-derived fungicide flusilazole and its germanium analogue: A computational approach to Si/Ge bioisosterism

Bioisosterism, a specific molecular alteration processing, is an effective approach used in agrochemical development studies as well as in pharmaceutical sciences. Analyzing some parameters such as size, volume, charge, aqueous/lipid solubility, polarizability, degree of hybridization, intra- and intermolecular interactions, which may be caused by bioisosteric changes, by using quantum chemical methods, provides speed and different perspectives to the studies. Towards this end, this study approached the Si/Ge bioisosterism from a computational perspective by performing DFT-based calculations on flusilazole, a widely used fungicide, and its germanium analogue. The reflections of the replacement of silicon with germanium in the structure of flusilazole on the structural parameters, frontier molecular orbital energies, quantum chemical descriptors and electrostatic surface properties were examined. Additionally, FT-IR spectra of the aforementioned molecules were visualized and investigated in detail. Natural bond orbital analyzes were also performed to determine the intermolecular interactions and their corresponding stabilization energies. Besides, 1-octanol/water partition coefficients (logPow), the quantitative identifier of lipophilicity, were calculated. It was determined that both molecules could exhibit similar lipophilic character with a difference of 0.09 logarithmic units in logPow value.

Protein Kinases as Potential Targets Contribute to the Development of Agrochemicals

Using agrochemicals against pest insects, fungi, and weeds plays a major part in maintaining and improving crop yields, which helps to solve the issue of food security. Due to the limited targets and resistance of agrochemicals, protein kinases are regarded as attractive potential targets to develop new agrochemicals. Recently, a lot of investigations have shown the extension of agrochemicals by targeting protein kinases, implying an increasing concern for this kind of method. However, few people have summarized and discussed the targetability of protein kinases contributing to the development of agrochemicals. In this work, we introduce the research on protein kinases as potential targets used in crop protection and discuss the prospects of protein kinases in the field of agrochemical development. This study may not only provide guidance for the contribution of protein kinases to the development of agrochemicals but also help nonprofessionals such as students learn and understand the role of protein kinases quickly.

DROPLET SIZE DISTRIBUTION PARAMETERIZATION FOR FLAT FAN SPRAYS OF AGRICULTURAL TANK MIXTURES

In agricultural spray application of pesticides, the volumetric droplet size distribution (VDSD) critically influences the efficacy of the application as well as the risk of off-target spray deposition. It is critical to have accurate predictions of the VDSD for development of new agrochemicals and spray nozzles. VDSD parameterization and subsequent prediction is complicated in agrochemical sprays by the unique geometries of the nozzles employed, which typically do not have clearly evident hydraulic diameters and vary in size, as well as by the effects of active herbicides and adjuvants on the spray. Herein, scaling based on conservation of energy is utilized to develop a relationship predicting the VDSD for flat fan sprays used in agrochemical application with agrochemical products. To examine the proposed scaling relationship, we made measurements of VDSDs using laser diffraction interferometry for agriculturally relevant tank mixtures, including active pesticides and both emulsion-forming and rheology-modifying drift control adjuvants, sprayed with complex geometry, flat fan nozzles typical of field application. We show that for three distinct nozzle types and three tank mixtures (nine combinations), VDSDs can be normalized by the Sauter mean diameter (<i>D<sub>32</sub></i>), and normalized distributions collapse for given nozzle type-spray tank mix combination. Subsequently, we show for all test combinations that the Sauter mean diameter normalized by the nozzle hydraulic diameter (<i>D<sub>H</sub></i>) scales with the ratio of product of tank mix surface tension and hydraulic diameter divided by the nozzle pressure drop, with a scaling exponent of 1/3.

One-pot Lewis acid assisted synthesis of indole-3-sulfonamide and imidazo[1,2-a]pyridine-3-sulfonamide using Burgess reagent in a microwave reactor

Indole-3-sulfonamides and imidazo[1,2-a]pyridine-3-sulfonamides have served as useful derivatives for development of useful therapeutics and agrochemicals. An efficient one-pot yet two step synthesis of these key derivatives was developed using a modified Burgess reagent and Lewis acids under microwave reaction conditions. A systematic study to optimize the synthetic yield of indole-3-sulfonamide, and subsequent application of the developed reaction condition for the synthesis of imidazo[1,2-a]pyridine derivatives is reported in this paper.