Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents

Ma, Dong; Yang, Yin; Chen, Ying-Lu; Yan, Yi-Tao; Wu, Jun

doi:10.1039/d1ra02663a

Cited by 7 publications

(6 citation statements)

References 65 publications

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“…Final evaluation was performed within 21 days of treatment by visual rating scales of 0–100%. The remaining conditions were set in accordance with the methodology described in the literature [ 52 ].…”

Section: Methodsmentioning

confidence: 99%

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Yan,

Chen,

et al. 2024

Molecules

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Herbicides are useful tools for managing weeds and promoting food production and sustainable agriculture. In this study, we report on the development of a novel class of lipophilic pyrimidine-biphenyl (PMB) herbicides. Firstly, three PMBs, Ia, IIa, and IIIa, were rationally designed via a scaffold hopping strategy and were determined to inhibit acetohydroxyacid synthase (AHAS). Computational simulation was carried out to investigate the molecular basis for the efficiency of PMBs against AHAS. With a rational binding mode, and the highest in vitro as well as in vivo potency, Ia was identified as a preferable hit. Furthermore, these integrated analyses guided the design of eighteen new PMBs, which were synthesized via a one-step Suzuki–Miyaura cross-coupling reaction. These new PMBs, Iba-ic, were more effective in post-emergence control of grass weeds compared with Ia. Interestingly, six of the PMBs displayed 98–100% inhibition in the control of grass weeds at 750 g ai/ha. Remarkably, Ica exhibited ≥ 80% control against grass weeds at 187.5 g ai/ha. Overall, our comprehensive and systematic investigation revealed that a structurally distinct class of lipophilic PMB herbicides, which pair excellent herbicidal activities with new interactions with AHAS, represent a noteworthy development in the pursuit of sustainable weed control solutions.

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Section: Methodsmentioning

confidence: 99%

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Yan,

Chen,

et al. 2024

Molecules

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“…The structures were confirmed by 1 H NMR, 13 C NMR, 19 F NMR, and HRMS. Pyrimidine compounds have demonstrated a diverse range of biological activities in previous studies, encompassing antiviral, antibacterial, fungicidal, insecticidal, and herbicidal properties [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Consequently, a variety of pyrimidine derivatives (Figure 1) have been successfully developed into commercial pesticides that have made significant contributions to the smooth functioning of agricultural production.…”

Section: Chemistrymentioning

confidence: 99%

“…Molecules 2023, 28, 6498 2 of 13 herbicidal properties [6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Consequently, a variety of pyrimidine derivatives (Figure 1) have been successfully developed into commercial pesticides that have made significant contributions to the smooth functioning of agricultural production.…”

Section: Introductionmentioning

confidence: 99%

Synthesis, Antifungal, and Antibacterial Activities of Novel Benzoylurea Derivatives Containing a Pyrimidine Moiety

An,

Lan,

Fei

et al. 2023

Molecules

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To explore more efficient and less toxic antibacterial and antifungal pesticides, we utilized 2,6-difluorobenzamide as a starting material and ultimately synthesized 23 novel benzoylurea derivatives containing a pyrimidine moiety. Their structures were characterized and confirmed by 1H NMR, 13C NMR, 19F NMR, and HRMS. The bioassay results demonstrated that some of the title compounds exhibited moderate to good in vitro antifungal activities against Botrytis cinerea in cucumber, Botrytis cinerea in tobacco, Botrytis cinerea in blueberry, Phomopsis sp., and Rhizoctonia solani. Notably, compounds 4j and 4l displayed EC50 values of 6.72 and 5.21 μg/mL against Rhizoctonia solani, respectively, which were comparable to that of hymexazol (6.11 μg/mL). Meanwhile, at 200 and 100 concentrations, the target compounds 4a–4w exhibited lower in vitro antibacterial activities against Xanthomonas oryzae pv. oryzicola and Xanthomonas citri subsp. citri, respectively, compared to those of thiodiazole copper. Furthermore, the molecular docking simulation demonstrated that compound 4l formed hydrogen bonds with SER-17 and SER-39 of succinate dehydrogenase (SDH), providing a possible explanation for the mechanism of action between the target compounds and SDH. This study represents the first report on the antifungal and antibacterial activities of novel benzoylurea derivatives containing a pyrimidine moiety.

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“…24 Previously, we have also found that compounds bearing the pyrimidinyloxybenzyl scaffold show consistent postemergence herbicidal activity against Digitaria sanguinalis. 25 Their herbicidal spectrum could be tuned with diverse substituents and motifs, among which the compound containing hydrophobic tetrahydrocarbazole motif (Figure 1a) showed the highest and broadest weed control efficiency. Diaryl ether is a versatile scaffold widespread in numerous natural products, 26 agrochemicals, 27 and pharmaceuticals.…”

Section: ■ Introductionmentioning

confidence: 99%

A Novel AHAS-Inhibiting Herbicide Candidate for Controlling Leptochloa chinensis: A Devastating Weedy Grass in Rice Fields

Chen,

Yan,

Chen

et al. 2024

J. Agric. Food Chem.

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Given the prevalence of the malignant weed Chinese Sprangletop (Leptochloa chinensis (L.) Nees) in rice fields, the development of novel herbicides against this weed has aroused wide interest. Here, we report a novel diphenyl ether-pyrimidine hybrid, DEP-5, serving as a systematic pre/postemergence herbicide candidate for broad-spectrum weed control in rice fields, specifically for L. chinensis. Notably, DEP-5 exhibits over 80% herbicidal activity against the resistant biotypes even at 37.5 g a.i./ha under greenhouse conditions and has complete control of L. chinensis at 150 g a.i./ha in the rice fields. We uncover that DEP-5 acts as a noncompetitive inhibitor of acetohydroxyacid synthase (AHAS) with an inhibition constant (K i ) of 39.4 μM. We propose that DEP-5 binds to AHAS in two hydrophobic-driven binding modes that differ from commercial AHAS inhibitors. Overall, these findings demonstrate that DEP-5 has great potential to be developed into a herbicide for L. chinensis control and inspire fresh concepts for novel AHAS-inhibiting herbicide design.

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Design, step-economical diversity-oriented synthesis of an N-heterocyclic library containing a pyrimidine moiety: discovery of novel potential herbicidal agents

Abstract: A diverse library of pyrimidine–N-heterocycle hybrids was developed through a step-economical diversity-oriented synthesis strategy. In vivo biological screening showed some derivatives exhibited significant potential herbicidal activity.

Cited by 7 publications

References 65 publications

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Discovery of a New Class of Lipophilic Pyrimidine-Biphenyl Herbicides Using an Integrated Experimental-Computational Approach

Synthesis, Antifungal, and Antibacterial Activities of Novel Benzoylurea Derivatives Containing a Pyrimidine Moiety

A Novel AHAS-Inhibiting Herbicide Candidate for Controlling Leptochloa chinensis: A Devastating Weedy Grass in Rice Fields

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