•A series of O-substituted trifluoroatrolactamide derivatives were synthesized.•Their structures were characterized by NMR, MS, IR, X-ray.•Some molecular properties were calculated by density functional theory calculations.•Good fungicidal activities were observed.A series of O-substituted trifluoroatrolactamide derivatives has been synthesized and fully characterized by 1H NMR, 13C NMR, 19F NMR, HRMS and X-ray diffraction analyses. The fungicidal activity of these compounds was evaluated and the results showed that some of them exhibited potent in vitro fungicidal activity against Erysiphe graminis and Pyricularia oryzae. Their structure-property relationships were investigated using density functional theory calculations. The X-ray crystal structure of one of these compounds adopted a monoclinic space group with the following unit cell parameters: a = 24.285 (13) Å, b = 9.006 (5) Å, c = 9.794 (5) Å, β = 92.110 (9)º, V = 2140.6 (19) Å3 and Z = 4. A comparison of these experimental results with the theoretical values revealed that there was good agreement between the two sets of data. The subsequent biological evaluation of these compounds showed that some of them exhibited potent in vitro fungicidal activity against Erysiphe graminis and Pyricularia oryzae.

A series of novel substituted 3,3,3-trifluoro-2-methoxy-N-methyl-N,2-diphenylpropanamides were synthesized from α-hydroxyacetamide using CH3I as the methylating agent. Their chemical structures were characterized by 1H NMR, 13C NMR, 19F NMR, and HRMS X-ray analysis. The dimethylated trifluoroatrolactamide exhibited moderate antifungal activity.

Exocyclic enamides have been used extensively in the synthesis of natural products and biologically active substances. A facile and efficient protocol has been developed for the synthesis of a series of new 5-methylenemorpholin-3-one derivatives, which are exocyclic enamides, based on the reactions of trifluoroatrolactamides with propargyl bromide in the presence of sodium hydride. The biological evaluation of these compounds showed that some of them exhibited very good in vitro fungicidal activity against P. oryzae. For example, compounds 2d and 2e gave fungicidal activities of 50% at a concentration of 0.9 μg mL−1, whilst the control compound fenaminstrobin gave 80% activity at the same concentration.

Valinamide carbamates are important agricultural fungicides with anti-oomycete activity and low toxicity toward mammalian cells. To find valinamide carbamates with high activity against resistant pathogens, a series of substituted 1-phenyl-2-phenoxyethylamino derivatives were designed and synthesized by introducing substituted phenyloxy or benzyloxy into valinamide carbamate leads. Bioassays showed that many title compounds exhibited good anti-oomycete activity. Compound 8b had much higher in vitro fungicidal activity against Phytophthora capsici than the control compound iprovalicarb and had a similar potency to the control mandipropamid. At 6.25 μg mL−1 the fungicidal activities of many compounds against in vivo Pseudoperonospora cubensis were greater than 30%, while the control dimethomorph gave only 27% activity at this concentration. The effect of 8b against Pseudoperonospora cubensis in the field indicates promise for a new candidate for controlling cucumber downy mildew.

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure–activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 μg mL−1.

•A new type of SDHI having a 1,2,3-triazole moiety was developed.•Most compounds exhibited good fungicidal activities.•Compounds featuring ester groups were as effective as those with amides.•Some of the title compounds displayed good larvicidal activity against mosquitoes.Succinate dehydrogenase inhibitors (SDHIs) are efficient fungicides that are widely used to control plant diseases caused by phytopathogenic fungi, although their effectiveness is undermined by the development of resistance across a range of different fungi. One of the most common structural features of SDHIs is their amide bond. The introduction of greater structural diversity to SDHIs is a promising strategy to delay the onset of resistance. A series of novel SDHIs containing a bioactive 1,2,3-triazole moiety have been designed and synthesized and their fungicidal and insecticidal activities evaluated. The results of these analyses show that most of the newly synthesized 1,2,3-trizole-4-carboxyl amide (ester) analogues exhibit good fungicidal activities, especially towards Sclerotinia sclerotiorum, and a structure–activity relationship study confirmed that the replacement of the amide group with an ester group had little effect on fungicidal activity, which could be provideous in terms of issues and metabolism. 1,6-Dimethyl phenyl was confirmed as the most efficient substituent of the current study when it was placed on both the amide and ester compounds. Interestingly, some of the newly synthesized compounds displayed good insecticidal activities against Culex pipiens pallens. The results of the current study show that these 1,2,3-triazole-4-carboxyl amide and ester analogues represent a new type of SDHI that could be used for the development of novel pesticides.

An ultrasound-promoted one-pot Passerini/hydrolysis reaction sequence has been developed for the synthesis of trifluoroatrolactamide derivatives using a diverse range of trifluoroacetophenones and isonitriles in acetic acid. Parallel synthesis in a centrifuge tube using a noncontact ultrasonic cell crusher was used in this study as an efficient method for the rapid generation of combinatorial trifluoroatrolactamide libraries, and subsequent biochemical evaluation of the resulting compounds indicated that they possessed excellent broad-spectrum fungicidal activities. N-(4-chlorophenyl)-2-(4-ethylphenyl)-3,3,3-trifluoro-2-hydroxypropanamide and N-(4-chlorophenyl)-3,3,3-trifluoro-2-hydroxy-2-(4-methoxyphenyl)propanamide, in particular, showed significant fungicidal activities against all of the fungal species tested in the current study.Keywords: fungicidal activities; one-pot Passerini/hydrolysis reaction; parallel synthesis; trifluoroatrolactamide library; ultrasound-promoted

A new method has been developed for the Michael addition of nitrogen- and carbon-containing nucleophiles to cyclic enones. Using this conjugate addition reaction, a variety of different nucleophiles can react with a range of cyclic enones in the presence of p-toluenesulfonic acid under solvent-free ultrasound irradiation conditions affording the corresponding C–N or C–C adducts in good to excellent yields. Comparatively, performing the reaction under ultrasound irradiation gives higher yields, is more efficient and environmentally benign than performing it at high pressure.

A facile, efficient and environmentally-friendly protocol for the synthesis of α-acyloxy amides has been developed by ultrasound-promoted sterically congested Passerini reactions under solvent-free conditions. This method provides several advantages over current reaction methodologies including a simpler work-up procedure, shorter reaction times and higher yields.

A series of novel fluorine-containing mandelic acid amide compounds were designed and synthesized by a facile method, and their structures were characterized by 1H nuclear magnetic resonance (NMR) and high-resolution mass spectrometry. The preliminary in vivo bioassays indicated that some of the title compounds showed excellent fungicidal activities in vivo against Pseudoperonospora cubensis at the dosage of 25 mg L−1, which were comparable with the control (Mandipropamid).Graphical abstractA series of novel fluorine containing mandelic acid amide compounds were designed and synthesized by a facile method, and their structures were characterized by 1H nuclear magnetic resonance (NMR) and high-resolution mass spectrometry. The preliminary fungicidal activities bioassays indicated that some of the title compounds showed excellent fungicidal activities in vivo against Pseudoperonospora cubensis at the dosage of 25 mg L−1, which are comparable with the control (Mandipropamid).Highlights► Novel fluorine containing mandelic acid amide compounds were synthesized. ► The title compounds showed excellent fungicidal activities. ► The fungicidal activity are closely related to degree of unsaturation of R2.

A series of new acrylamide derivatives containing 1,2,3-thiadiazole were synthesized, characterized, and evaluated for their anti-hepatitis B virus (HBV) activities in vitro. The IC50 of compounds 9b (10.4 μg/mL), 9c (3.59 μg/mL) and 17a (9.00 μg/mL) of the inhibition on the replication of HBV DNA were higher than that of the positive control lamivudine (14.8 μg/mL). Compound 9d exhibited significant activity against secretion of HBeAg (IC50 = 12.26 μg/mL).A series of new acrylamide derivatives containing 1,2,3-thiadiazole were synthesized, characterized and tested in vitro against HBV. Some of the new compounds display excellent activity against DNA reproduction and against HBeAg of HBV.

Carboxylic acid amide (CAA) fungicides are an important class of agricultural fungicide with oomycete activity and low toxicity toward mammalian cells. To find CAA analogues with high activity against resistant pathogens, a series of substituted N-benzhydryl valinamide carbamate derivatives were designed and synthesized by introducing substituted aromatic rings into valinamide carbamate leads. Bioassays showed that some title compounds exhibited very good in vitro fungicidal activity against Phytophthora capsici and in vivo fungicidal activities against Pseudoperonospora cubensis. Topomer CoMFA was performed to explore the structure–activity relationship on the basis of the in vitro data. The dimethoxy substituted aromatic analogue 9e was found to display higher in vitro fungicidal activity against Phytophthora capsici than iprovalicarb but lower activity than mandipropamid, and higher in vivo fungicidal activity against Pseudoperonospora cubensis than dimethomorph at a dosage of 6.25 μg mL−1.