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Cytochrome bc1 complex (complex Ⅲ) is one of the most important targets for drug and fungicide discovery. Metyltetraprole (MET) is a novel inhibitor of complex Ⅲ, which has activity against the major reported mutations G143A and F129L of quinone site inhibitor (QoI)-resistant isolates. However, the anti-resistance mechanism of MET is still elusive and very intriguing to be explored. Here, we determined the near-atomic resolution structures of isolated complex III (2.88 Å) and MET-bound complex III (3.26 Å) by cryo-electron microscopy (cryo-EM), showing that MET exhibited a different binding mode from azoxystrobin, a typical QoI. MET could bind to the G143A or F129L mutated complex as well as to the wild-type complex III, whereas the binding affinity of azoxystrobin to the G143A or F129L mutants decreased significantly compared to the wild-type. This work provided a structural basis for the design of the next generation of inhibitors to overcome the resistance.

Novel and potent inhibitors targeting succinate-ubiquinone oxidoreductase were discovered from the natural product sclerotiorin for the first time.

Herbicide resistance has become one of the foremost problems in crop production worldwide. New herbicides are required to manage weeds that have evolved resistance to the existing herbicides. However, relatively few herbicides with new modes of action (MOAs) have been discovered in the past two decades. Therefore, the discovery of new herbicides (i.e., new chemical classes or MOAs) remains a primary but ongoing strategy to overcome herbicide resistance and ensure crop production. In this mini-review, starting with the inherent characteristics of the target proteins and the inhibitor structures, we propose two strategies for the rational design of new herbicides and one computational method for the risk evaluation of target mutation-conferred herbicide resistance. The information presented here may improve the utilization of known targets and inspire the discovery of herbicides with new targets. We believe that these strategies may trigger the sustainable development of herbicides in the future. © 2021 Society of Chemical Industry.

The marine natural product neopeltolide was isolated from a deep-water sponge specimen of the family Neopeltidae. Neopeltolide has been proven to be a new type of inhibitor of the cytochrome bc1 complex in the mitochondrial respiration chain. However, its detailed inhibition mechanism has remained unknown. In addition, neopeltolide is difficult to synthesize because of its very complex chemical structure. In the present work, the binding mode of neopeltolide was determined for the first time by integrating molecular docking, molecular dynamics simulations, and molecular mechanics Poisson-Boltzmann surface area calculations, which showed that neopeltolide is a Qo site inhibitor of the bc1 complex. Then, according to guidance via inhibitor-protein interaction analysis, structural modification was carried out with the aim to simplify the chemical structure of neopeltolide, leading to the synthesis of a series of new neopeltolide derivatives with much simpler chemical structures. The calculated binding energies (Δ Gcal) of the newly synthesized analogues correlated very well ( R2 = 0.90) with their experimental binding free energies (Δ Gexp), which confirmed that the computational protocol was reliable. Compound 45, bearing a diphenyl ether fragment, was successfully designed and synthesized as the most potent candidate (IC50 = 12 nM) against porcine succinate cytochrome c reductase. The molecular modeling results indicate that compound 45 formed a π-π interaction with Phe274 and two hydrogen bonds with Glu271 and His161. The present work provides a new starting point for future fungicide discovery to overcome the resistance that the existing bc1 complex inhibitors are facing.

The cytochrome bc1 complex (the bc1 complex or complex III) is an attractive target for the discovery of numerous pharmaceuticals and pesticides. In order to identify new lead structures for this target, a new series of molecules, N-(4-aryloxyphenyl)phthalimides, were designed and synthesized in a straightforward manner. Our design strategy was to introduce a 4-aryloxyphenyl group, a fragment which exhibited promising bc1 complex-inhibiting properties, into the aryl group of the valuable N-arylphthalimide backbone. Afterward, the biochemical evaluation of the newly synthesized compounds was carried out, and the results implied that several compounds demonstrated good activities against succinate-cytochrome reductase (SCR, a mixture of mitochondrial complex II and the bc1 complex). Further studies confirmed that 3e′, a representative compound in this paper, was identified as an inhibitor of the bc1 complex. Furthermore, computational simulations were also performed to better understand binding of 3e′ to the enzyme complex, which indicated that 3e′ should bind to the Qo site of the bc1 complex. Consequently, we harbor the idea that this paper can provide a solid platform for synthesis and discovery of other bc1 complex inhibitors.

Pyridalyl is an insecticide that shows significant efficacy against Plutella xylostella, a notorious pest insect worldwide. In this study, we monitored resistance of P. xylostella to pyridalyl in China from 2016 to 2017, determined cross-resistance, inheritance, and synergism of pyridalyl resistance in two pyridalyl-resistant populations, one field-evolved resistant population (ZL-PR) and one laboratory-selected resistant population (XY-PR). We found that variation in susceptibility among 15 field populations in China from 2016 to 2017 was high, with mean LC50 values ranging from 1.839 to 1,652 mg/liter. The laboratory-selected XY-PR strain showed 31.3-fold resistance to pyridalyl and moderate cross-resistance to fipronil. The ZL-PR displayed 1,050.2-fold resistance to pyridalyl and high resistance to all tested insecticides. Genetic analysis illustrated that pyridalyl resistance in ZL-PR was autosomally inherited and incompletely recessive. However, pyridalyl resistance in the XY-PR strain was autosomally inherited but incompletely dominant. Moreover, piperonyl butoxide significantly inhibited pyridalyl resistance in the XY-PR strain. In conclusion, P. xylostella field populations from South China have high levels of resistance to pyridalyl and different modes of inheritance of resistance were found in XY-PR and ZL-PR. Moreover, enhanced oxidative metabolism is possibly involved in resistance of the XY-PR strain but not in the ZL-PR strain.

Succinate-cytochrome c reductase (SCR) is composed of a mixture of mitochondrial complex II (succinate-ubiquinone oxidoreductase) and complex III (cytochrome bc1 complex). Meanwhile, complexes II and III are two promising targets of numerous antibiotics and fungicides. With an aim to identify new lead structures for SCR, complex II or III, a new series of 4-aryloxy-N-arylanilines were synthesized by introducing a 4-aryloxy phenyl group as one of the aryl groups in diaryl amines. With the economic Cu(OAc)2·H2O as the optimal copper promoter, a simple and facile protocol was utilized to afford 24 target products in 56-93% yields. Furthermore, extensive screening results suggested variable inhibitory activities of these compounds against SCR. Exceptionally, compounds 7k-7n showed excellent inhibition potency with their IC50 values in the nanomolar range, demonstrating higher potency than the commercial controls (penthiopyrad and azoxystrobin) by over one order of magnitude.

The respiratory chain succinate–ubiquinone oxidoreductase (SQR or complex II) is a promising target for fungicide discovery. As a continuation of our research work on the development of new fungicides, a series of bitriazolyl compounds were designed and synthesized in excellent yields by an ionic liquid promoted 1,3-dipolar Huisgen cycloaddition reaction of azides and akynes. These newly synthesized compounds were characterized by 1H NMR, 13C NMR and HR-MS spectroscopy. The in vitro assay indicated that several compounds displayed good inhibitory effects against porcine succinate–cyctochrome reductase (SCR) with IC50 values ranging from 2.89 to 61.19 μM. Compound 1b with an IC50 value of 2.89 μM, comparable to the commercial control penthiopyrad, was identified as the most promising inhibitor. Further evaluation of the representative compounds against respective SQR and cyt bc1 indicated that their inhibitory potency against SQR was much higher than that against cyt bc1, suggesting that SQR might be a potential target of these inhibitors. Furthermore, molecular docking studies suggested that strong hydrogen bonding and π–π stacking interactions might be responsible for a higher SQR inhibitory effect of compound 1b as compared to that of compounds 1d and 2b. Consequently, bitriazolyl compounds, a totally new skeleton that is distinct from the existing commercial SQR-inhibiting fungicides, were discovered, which could potentially be a new lead for further development of SQR inhibitors.

4-Aryl-3,4-dihydrocoumarins are a class of valuable molecules demonstrating attractive pharmaceutical and biological properties. In this paper, we designed a new and facile approach to synthesis of 4-aryl-3,4-dihydrocoumarin derivatives by Bronsted acid catalyzed Friedel–Crafts alkylation and cycloaddition reaction. With this protocol, 15 examples of 4-aryl-3,4-dihydrocoumarins were successfully prepared with yields ranging from 82 to 99%.

Protoporphyrinogen oxidase (PPO, E.C. 1.3.3.4) is known as a key action target for several structurally diverse herbicides. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel 3-(2'-halo-5'-substituted-benzothiazol-1'-yl)-1-methyl-6-(trifluoromethyl)pyrimidine-2,4-diones 9 were designed and synthesized. The bioassay results indicated that a number of the newly synthesized compounds exhibited higher inhibition activity against tobacco PPO (mtPPO) than the controls, saflufenacil and sulfentrazone. Compound 9F-5 was identified as the most potent inhibitor with a Ki value of 0.0072 μM against mtPPO, showing about 4.2-fold and 1.4-fold higher potency than sulfentrazone (Ki = 0.03 μM) and saflufenacil (Ki = 0.01 μM), respectively. An additional green house assay demonstrated that compound 9F-6 (Ki = 0.012 μM) displayed the most promising postemergence herbicidal activity with a broad spectrum even at a concentration as low as 37.5 g of active ingredient (ai)/ha. Maize exhibits relative tolerance against compound 9F-6 at the dosage of 150 g ai/ha, but it is susceptible to saflufenacil even at 75 g ai/ha. Thus, compound 9F-6 exhibits the potential to be a new herbicide for weed control in maize fields.

The cytochrome bc1 complex (cyt bc1 or complex III) is a promising target of numerous antibiotics and fungicides. With an aim to indentify new lead structures for the bc1 complex, a series of novel inhibitors were discovered from the natural product karrikinolide for the first time. Extensive screening results suggested variable inhibitory activities of these compounds against succinate-cytochrome reductase [SCR, a mixture of respiratory complex II (SQR) and complex III (the bc1 complex)], implying the essential role of a 4-substituted phenyl group for the high potency. Exceptionally, compound 12g showed excellent inhibition potency having an IC50 value in the sub-micromolar range, demonstrating its higher potency than the commercial control amisulbrom by over two orders of magnitude. Further experiments inferred that these newly prepared compounds mainly target the bc1 complex. Seemingly, this work has presented a new lead scaffold for further development of bc1 complex inhibitors.

Recently, a class of dehydrogenative transformations for amide bond formation have been developed. These transformations are atom-economic and environmentally-benign processes with their respective starting materials of alcohols and amines, aldehydes and amines, as well as symmetrical esters and amines, showing a promising prospect for applications. These unique protocols have been reported using various ruthenium-based catalytic systems. However, challenges still exist in this area. For example, existing catalytic systems usually suffer from low efficiency, high catalyst loading, and lack of structural diversity.

As an important fragment and synthetic intermediate, functionalized 6-arylsalicylate substructure widely exist in pharmacologically relevant natural products and bioactive compounds. In our recent works, we discovered two highly potent inhibitors for combating mutants of acetohydroxyacid synthase (AHAS), an important target for herbicide discovery. These two inhibitors contain 6-arylsalicylate skeleton. Previously, we have explored a new method to synthesize position-6 aryl substituted salicylic acid fragment. However, this method failed to synthesize 4-methyl-6-aryl salicylic acids. Herein, we developed a new efficient method for the synthesis of functionalized 4-methyl-6-bulkyarylsalicylates via a microwave-promoted Suzuki cross-coupling. This method has obvious advantages, such as a wide range of substrates, smooth and rapid reaction, moderate to excellent yields. Due to its superiority to the traditional available methods, this protocol could be utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.

Respiratory chain succinate-ubiquinone oxidoreductase (SQR or complex II) and ubihydroquinone-cytochrome (cyt) c oxidoreductase (cyt bc1 or complex III) have been demonstrated as the promising targets of numerous antibiotics and fungicides. As a continuation of our research work on the development of new fungicides, a series of 1,2,4-triazole-1,3-disulfonamide derivatives with dual functions targeting both SQR and cyt bc1 were designed and synthesized by coupling diverse diphenyl ether moieties with triazolesulfonamide units. These newly synthesized compounds were characterized by elemental analyses, 1H NMR and ESI-MS spectrometry. The in vitro assay indicated that most of the synthesized compounds displayed good inhibition against porcine succinate-cytochrome reductase (SCR) with IC50 values ranging from 3.2 to 81.8 μM, revealing much higher activity than that of the commercial control amisulbrom whose IC50 value is 93.0 μM. Further evaluation against the respective SQR and cyt bc1 indicated that most compounds exhibited SQR-inhibiting activity as well as cyt bc1-inhibiting activity, but the inhibition potency against SQR is much higher than that against cyt bc1, showing that the SCR inhibition might be contributed greatly by the SQR inhibition. The further antibacterial evaluation against Xanthomonas oryzae pv. oryzae revealed that four compounds showed excellent potency at the concentration of 20 μg mL−1. In particular, compounds 6h and 6j exhibited much better antibacterial activity than the commercial control bismerthiazol in terms of their EC50. Impressively, 6j has an EC90 of 33.62 μg mL−1, more than 10-fold higher than that of bismerthiazol.

Isatin (1H-indole-2,3-dione, ) was first obtained by Erdman and Laurent in 1841 as a product from the oxidation of indigo by nitric and chromic acids.1 Since then, isatin and its derivatives have b...

Background Pyridalyl is a highly active insecticide against lepidopterous larvae, with a novel chemical structure not related to any other existing insecticide. To discover new pyridalyl analogues with high activity against resistant pests, a series of 1,1-dichloropropene derivatives bearing structurally diverse substituted heterocycle rings in place of the pyridine ring of pyridalyl were designed and synthesised. Results All of the title compounds were confirmed by (1)H NMR, (13)C NMR and high-resolution mass spectra. Two representative compounds (Ic and IIa) were further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed good insecticidal activity against Prodenia litura. Further determination of LD50 values and field trials identified compound IIa as the most promising candidate, which produced a much better 14 day control effect against diamondback moths and longer duration of efficacy than pyridalyl, indicating its potential for further development as a new insecticide for the control of lepidopteran insects. Conclusion Compound IIa has great potential for further development as a new insecticide for the control of lepidopteran insects.

Pyrazoles and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. In contrast to 3 or 5-aryl pyrazole, the preparation of 4-aryl pyrazole is fairly rare. Utilizing microwave irradiation, the synthesis of 4-substituted-arylpyrazole via Suzuki cross-coupling has been developed with a wide range of substrates. The remarkable advantages of this method are mild reaction conditions, simple operation, high yield, and short reaction time. Product structures were identified by MS, 1H NMR, 13C NMR, and elemental analysis.

Functionalized 6-substituted-thiosalicylates are key intermediates for the synthesis of pyrimidinyl(thio)salicylic acids, a group of important herbicides targeting plant acetohydroxyacid synthase. Therefore, it is of great interest to develop an efficient method for the syntheses of 6-substituted-thiosalicylates. Herein, we have developed a direct and efficient method for the synthesis of functionalized 6-substituted-thiosalicylates (4) from aryl iodide (1) by using an improved microwave-assisted Suzuki cross-coupling reaction. Almost all the reactions proceeded smoothly and afforded moderate to excellent yields of products. Moreover, this protocol is obviously superior to the traditional available methods and could be utilized to synthesize pyrimidinyl(thio)salicylic acid and its derivatives.

A mild and facile approach to the title compounds, which are of interest in natural product and medicinal chemistry, becomes optimal in the presence of HClO4.

Recently, a class of dehydrogenative transformations for amide bond formation have been developed. These transformations are atom-economic and environmentally-benign processes with their respective starting materials of alcohols and amines, aldehydes and amines, as well as symmetrical esters and amines, showing a promising prospect for applications. These unique protocols have been reported using various ruthenium-based catalytic systems. However, challenges still exist in this area. For example, existing catalytic systems usually suffer from low efficiency, high catalyst loading, and lack of structural diversity.

The synthesis of albucidin and its enantiomer are described. It involves a visible-light photocatalysis deiodination at the late stage. The absolute configuration of natural albucidin is determined as (1R,3S). This work provides a basis for structural modification to develop a new type of herbicidal from an old structure.

A new efficient method for the synthesis of functionalized 4-methyl-6-bulkyarylsalicylates via a microwave-promoted Suzuki cross-coupling is presented.

Sclerotiorin, a chlorine-containing azaphilone-type natural product, was first isolated from Penicillium sclerotiorum and has been reported to exhibit weak fungicidal activity. Optimization of the substituents at the 3- and 5-positions of the sclerotiorin framework was investigated with the aim of discovering novel fungicides with improved activity. The design of sclerotiorin analogues involved replacing the diene side chain with a phenyl group or an aromatic- or heteroaromatic-containing aliphatic side chain. The designed compounds were synthesized by cycloisomerization and subsequent oxidation of suitable 2-alkynylbenzaldehydes, in which a variety of substituents were introduced using a Sonogashira coupling reaction. The structures of these newly prepared compounds were confirmed by 1H and 13C NMR spectroscopy, HRMS and single-crystal X-ray analysis. The antifungal activity of the synthesized compounds was evaluated against seven phytopathogenic species. Compounds 3, 9g and 9h were found to have a broad spectrum of fungicidal activity, and these structurally simpler products can be recognized as lead compounds for further optimization.

A novel three-component reaction of o-bromobenzaldehyde, terminal alkynes and tert-butyl amine has been established, which proceeded smoothly to give 3-substituted isoquinolines in good yields in the presence of palladium/copper catalysts under microwave irradiation.

Sclerotiorin 1, first isolated from Penicillium sclerotiorum, has weak antifungal activity and belongs to the azaphilone-type family of natural products. Several series of sclerotiorin analogues were designed and synthesized with the aim of discovering novel fungicides with improved activity. The syntheses involved two key steps, cycloisomerization and then oxidation, and used a simple and efficient Sonogashira cross-coupling reaction to construct the required functionalized precursor. With sclerotiorin as a control, the activities of the newly synthesized analogues were evaluated against seven fungal pathogens, and several promising candidates (compounds 3a₁, 3d₂, 3e₂, 3f₂ and 3k₂) with greater activity and simpler structures than sclerotiorin were discovered. In addition, preliminary structure-activity relationships were studied, which revealed that not only the chlorine or bromine substituent at the 5-position of the nucleus but also the phenyl group at the 3-position and the substituent pattern on it contributed crucially to the observed antifungal activity. Analogues with a methyl substituent at the 1-position have reduced levels of activity, while those with a free hydroxyl group in place of acetoxy at the quaternary center of the bicyclic ring system retain activity.

Protoporphyrinogen oxidase (Protox, EC 1.3.3.4) has attracted great interest during the last decades due to its unique biochemical characteristics and biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, 23 new 1,3,4-thiadiazol-2(3H)-ones bearing benzothiazole substructure were designed and synthesized. The in vitro assay indicated that the newly synthesized compounds 1a–w displayed good inhibition activity against human PPO (hPPO) with Ki values ranging from 0.04 μM to 245 μM. To the knowledge, compound 1a, O-ethyl S-(5-(5-(tert-butyl)-2-oxo-1,3,4-thiadiazol-3(2H)-yl)-6-fluorobenzothiazol-2-yl)carbonothioate, with the Ki value of 40 nM, is so far known as the most potent inhibitor against hPPO. Based on the molecular docking and modified molecular mechanics/Poisson–Boltzmann surface area (MM-PBSA) calculations, the quantitative structure–activity relationships of 1,3,4-thiadiazol-2(3H)-ones and 1,3,4-oxadiazol-2(3H)-one derivatives were established with excellent correlation relationships (r2 = 0.81) between the calculated and experimental binding free energies. Some important insights were also concluded for guiding the future rational design of new hPPO inhibitors with improved potency.

Discovery of protoporphyrinogen oxidase (PPO, EC 1.3.3.4) inhibitors has been one of the hottest research areas in the field of herbicide development for many years. As a continuation of our research work on the development of new PPO-inhibiting herbicides, a series of novel N-(benzothiazol-5-yl)-4,5,6,7-tetrahydro-1H-isoindole-1,3(2H)-diones (1a-p) and N-(benzothiazol-5-yl)isoindoline-1,3-diones (2a-h) were designed and synthesized according to the ring-closing strategy of two ortho-substituents. The bioassay results indicated that some newly synthesized compounds exhibited higher PPO inhibition activity than the control of sulfentrazone. Compound 1a, S-(5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl) O-methyl carbonothioate, was identified as the most potent inhibitor with k(i) value of 0.08 μM, about 9 times higher than that of sulfentrazone (k(i) = 0.72 μM). Further green house assay showed that compound 1b, methyl 2-((5-(1,3-dioxo-4,5,6,7-tetrahydro-1H-isoindol-2(3H)-yl)-6-fluorobenzothiazol-2-yl)thio)acetate, exhibited herbicidal activity comparable to that of sulfentrazone even at a concentration of 37.5 g ai/ha. In addition, among six tested crops, wheat exhibited high tolerance to compound 1b even at a dosage of 300 g ai/ha. These results indicated that compound 1b might have the potential to be developed as a new herbicide for weed control of wheat field.

Phenyltriazolinones are one of the most important classes of herbicides targeting the protoporphyrinogen oxidase enzyme. A series of triazolinone derivatives containing a strobilurin pharmacophore were designed and synthesized with the aim of discovering new phenyltriazolinone analogues with high activity. The herbicidal activity of the synthesized compounds was assayed and some of the test compounds displayed moderate herbicidal activity at 150 g ai/ha.

The characteristics of low application rates, good crop selectivity, low residue and environmental safety exhibited by Protoporphyrinogen oxidase (PPO, EC 1.3.3.4)-inhibiting herbicides have attracted a world-wide research interests. As continuation of our research work on the development of new PPO inhibitors, a series of mono-carbonyl analogues of cyclic imides, N-phenyl pyrrolidin-2-ones and N-phenyl-1H-pyrrol-2-ones, were designed and synthesized based on previously established DFT-QSAR results. The PPO inhibition activities of 29 newly synthesized compounds were tested and a predictive comparative molecular field analysis (CoMFA) model was established with the conventional correlation coefficient r(2)=0.980 and the cross-validated coefficient q(2)=0.518. According to the CoMFA model, the substituent effects on the PPO inhibition activity were explained reasonably. Further greenhouse assay showed that 2-(4-chloro-2-fluoro-5-propoxy-phenyl)-2,3,4,5,6,7-hexahydro-isoindol-1-one (C(6), k(i)=0.095μM) and 2-(5-allyloxy-4-chloro-2-fluorophenyl)-2,3,4,5,6,7-hexahydro-isoindol-1-one (C(7), k(i)=0.12μM) displayed excellent post-emergency herbicidal activity at the concentration of 150g.ai/ha against seven tested weeds. Due to their high PPO inhibition effect and broad spectrum herbicidal activity, these two compounds have the potential for further study on crop selectivity and field trial. These results confirmed once again that only one of the carbonyl groups of cyclic imides is essential to the PPO inhibition activity.

Pyrazoles and their derivatives are important heterocycles found in nature and present in numerous bioactive compounds. In contrast to 3 or 5-aryl pyrazole, the preparation of 4-aryl pyrazole is fairly rare. Utilizing microwave irradiation, the synthesis of 4-substituted-arylpyrazole via Suzuki cross-coupling has been developed with a wide range of substrates. The remarkable advantages of this method are mild reaction conditions, simple operation, high yield, and short reaction time. Product structures were identified by MS, 1H NMR, 13C NMR, and elemental analysis.

Isatin (1H-indole-2,3-dione, ) was first obtained by Erdman and Laurent in 1841 as a product from the oxidation of indigo by nitric and chromic acids.1 Since then, isatin and its derivatives have b...

The improved microwave assisted Suzuki cross-coupling of aryl iodides (I) with boronic acids followed by deprotection produces various thiosalicylates.

Pyridalyl is a highly active insecticide against lepidopterous larvae, with a novel chemical structure not related to any other existing insecticide. To discover new pyridalyl analogues with high activity against resistant pests, a series of 1,1-dichloropropene derivatives bearing structurally diverse substituted heterocycle rings in place of the pyridine ring of pyridalyl were designed and synthesised.All of the title compounds were confirmed by (1)H NMR, (13)C NMR and high-resolution mass spectra. Two representative compounds (Ic and IIa) were further characterised by X-ray diffraction analysis. In addition, bioassays showed that most of the newly synthesised compounds displayed good insecticidal activity against Prodenia litura. Further determination of LD50 values and field trials identified compound IIa as the most promising candidate, which produced a much better 14 day control effect against diamondback moths and longer duration of efficacy than pyridalyl, indicating its potential for further development as a new insecticide for the control of lepidopteran insects.Compound IIa has great potential for further development as a new insecticide for the control of lepidopteran insects.

Protoporphyrinogen oxidase (EC 1.3.3.4) is one of the most significant targets for a large family of herbicides. As part of our continuous efforts to search for novel protoporphyrinogen oxidase-inhibiting herbicides, N-(benzothiazol-5-yl)tetrahydroisoindole-1,3-dione was selected as a lead compound for structural optimization, leading to the syntheses of a series of novel N-(benzothiazol-5-yl)hexahydro-1H-isoindole-1,3-diones (1a-o) and N-(benzothiazol-5-yl)hexahydro-1H-isoindol-1-ones (2a-i). These newly prepared compounds were characterized by elemental analyses, (1) H NMR, and ESI-MS, and the structures of 1h and 2h were further confirmed by X-ray diffraction analyses. The bioassays indicated that some compounds displayed comparable or higher protoporphyrinogen oxidase inhibition activities in comparison with the commercial control. Very promising, compound 2a, ethyl 2-((6-fluoro-5-(4,5,6,7-tetrahydro-1-oxo-1H-isoindol-2(3H)-yl)benzo[d]thiazol-2-yl)-sulfanyl)acetate, was recognized as the most potent candidate with K(i) value of 0.0091 μm. Further greenhouse screening results demonstrated that some compounds exhibited good herbicidal activity against Chenopodium album at the dosage of 150 g/ha.

Sclerotiorin, a chlorine-containing azaphilone-type natural product, was first isolated from Penicillium sclerotiorum and has been reported to exhibit weak fungicidal activity. Optimization of the substituents at the 3- and 5-positions of the sclerotiorin framework was investigated with the aim of discovering novel fungicides with improved activity. The design of sclerotiorin analogues involved replacing the diene side chain with a phenyl group or an aromatic- or heteroaromatic-containing aliphatic side chain. The designed compounds were synthesized by cycloisomerization and subsequent oxidation of suitable 2-alkynylbenzaldehydes, in which a variety of substituents were introduced using a Sonogashira coupling reaction. The structures of these newly prepared compounds were confirmed by 1H and 13C NMR spectroscopy, HRMS and single-crystal X-ray analysis. The antifungal activity of the synthesized compounds was evaluated against seven phytopathogenic species. Compounds 3, 9g and 9h were found to have a broad spectrum of fungicidal activity, and these structurally simpler products can be recognized as lead compounds for further optimization.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has attracted continuous interest during the last few decades not only because of its unique biochemical characteristics but also because of its biomedical significance. As a continuation of our research work on the development of new PPO inhibitors, N-(benzothiazol-5-yl)-hexahydro-2H-isoindole-1,3-dithione (1a–j) and N-(benzothiazol-5-yl)-octahydro-3-thioxoisoindol-1-one derivatives (2a–i) were designed and synthesized. These newly prepared compounds were characterized by elemental analyses, 1H NMR and ESI-MS spectroscopy. The in vitro assay indicated that these compounds displayed good inhibition activity against human PPO (hPPO) with Ki values ranging from 0.38 μM to 6.83 μM. Notably, most of the monothionated products (1a–j) displayed a higher or comparable PPO-inhibition activity compared with the commercial control sulfentrazone. The comparison of the dihedral angles of the representative compound with that of acifluorfen (ACF) complexed with hPPO clearly indicated that the dihedral angle between the thionyl amide or carbonyl amide ring and the benzothiazole ring was closely related to the variation of the PPO inhibition activity of different types of inhibitors.

In the title compound, C17H18N4O3, which displays good herbicidal activity, the planar bicyclic triazolopyrimidine system is bound to the benzoic acid isoprop­yl ester moiety via an O bridge. The dihedral angle formed by the bicylic triazolopyrimidine system and the benzene ring is 106.2 (2)°. Neither intra- nor inter­molecular hydrogen bonds are found.