Design, synthesis, and structure-activity relationship of novel aniline derivatives of chlorothalonil.

Chlorothalonil with both low cost and low toxicity is a popularly used fungicide in the agrochemical field. The presence of nucleophilic groups on this compound allows further chemical modifications to obtain novel chlorothalonil derivatives. Fluazinam, another commercially available agent with a broad fungicidal spectrum, has a scaffold of diaryl amine structure. To mimic this backbone structure, a variety of (un)substituted phenyl amines was used as nucleophilic agents to react with chlorothalonil to obtain compounds with a diphenyl amine structure. Via an elegant design, two leads, 2,4,5-trichloro-6-(2,4-dichlorophenylamino)isophthalonitrile (7) and 2,4,5-trichloro-6-(2,4,6-trichlorophenylamino)isophthalonitrile (11), with potential fungicidal activity were discovered after a preliminary bioassay screen. These two leads were further modified to obtain final products by replacing the chlorine groups in the phenyl ring in phenyl amine with other functional groups. These functional groups with various electronic properties and spatial characteristics were considered to explore the relationship between structure and fungicidal activity. The results indicate that the electron-withdrawing group NO2 on the 4 position on the right phenyl ring plays a unique role on enhancing the fungicidal activity. The compounds were identified by proton nuclear magnetic resonance and elemental analysis. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activities against cucumber downy mildew at 25 mg/L. Compound 20 has been shown as the optimal structure with 85% control against cucumber downy mildew at 6.25 mg/L concentration. The relationship between structure and fungicidal activity is reported. The present work demonstrates that chlorothalonil derivatives can be used as possible lead compounds for developing novel fungicides.

Design, synthesis and structure-activity relationship of novel coumarin derivatives.

BACKGROUND: The lead coumarin derivative (E)-methyl 3-methoxy-2-[2-(4-methylcoumarin-7-yloxymethyl)phenyl]acrylate was discovered by using an intermediate derivatisation method. To discover new coumarin derivatives with improved activity, a series of substituted coumarins were synthesised and bioassayed. RESULTS: The compounds were identified by ¹H NMR, IR, MS and elemental analysis. Bioassays demonstrated that some of the title compounds exhibited excellent fungicidal activity against cucumber downy mildew at 25 mg L⁻¹. The relationship between structure and fungicidal activity is reported. CONCLUSION: The present work demonstrates that coumarin derivatives containing methoxyacrylate moieties can be used as possible lead compounds for developing novel fungicides.

Synthesis and bioactivity of novel coumarin derivatives.

A series of coumarin derivatives (6-8) containing (E)-methyl 2-(methoxyimino)-2-phenylacetate, (E)-2-(methoxyimino)-N-methyl-2-phenylacetamide and methyl methoxy(phenyl)carbamate were synthesized from substituted resorcinols (1) and substituted beta-keto esters (2) as starting material via cyclization and condensation reactions. The test results indicated that (E)-methyl 2-{2-[(3-hexyl-4-methyl-coumarin-7-yloxy)methyl]phenyl}-2-(methoxyimino)acetate (6f) was the optimal structure with good fungicidal activity against cucumber grey mold (CGM) giving 100% control at 100 mg L(-1) concentration, much higher than that of coumoxystrobin. Methyl 2-[(3,4-dimethyl-coumarin -7-yloxy)methyl]phenyl(methoxy)carbamate (8a) was another optimal structure with good fungicidal activity against wheat powdery mildew (WPM) showing 100% control at 50 mg L(-1) concentration, at the same level as that of the commercial kresoxim-methyl, and very significantly higher than that of coumoxystrobin (no control against WPM at 400 mg L(-1)).

Synthesis and biological activity of new (E)-alpha-(Methoxyimino)benzeneacetate derivatives containing a substituted pyrazole ring.

Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with high activity, a series of new strobilurin derivatives containing a substituted pyrazole in the side chain were synthesized and their biological activities were tested. The compounds were identified by (1)H nuclear magnetic resonance, infrared, and elemental analysis. The test results indicated that the compounds exhibited strong fungicidal activities against Pyricularia oryzae , Phytophthora infestans , Pseudoperonospora cubensis , and Erysiphe graminis . The relationship between structure and biological activity is discussed in terms of the effects of the substituents on the pyrazole ring. The present work demonstrates that strobilurin analogues with a 3-(substituted phenyl)-1H-pyrazol-5-oxy side chain can be used as possible lead compounds for the development of potential agrochemicals.

Design, synthesis and biological activities of new strobilurin derivatives containing substituted pyrazoles.

BACKGROUND: Strobilurins are one of the most important classes of agricultural fungicides. To discover new strobilurin analogues with high activity, a series of new strobilurin derivatives containing substituted pyrazoles in the side chain were synthesised and bioassayed. RESULTS: The compounds were identified by (1)H NMR, IR, MS and elemental analysis. Preliminary bioassays indicated that some title compounds exhibited excellent fungicidal activities against Pseudoperonospora cubensis (Burk. & Curt.) Rostovsev and Erysiphe graminis DC f. sp. tritici Marchal, protecting cucumber and wheat at 6.25 and 1.56 mg L(-1) respectively, and showed a moderately high acaricidal activity against Tetranychus cinnabarinus (Boisd.) at 20 mg L(-1). The relationship between structure and biological activity is discussed in terms of effects of the substituent of the pyrazole ring. CONCLUSION: The present work demonstrates that strobilurin analogues with substituted phenylpyrazolylmethoxymethyl side chains can be used as possible lead compounds for further developing novel fungicides and acaricides.

Design, synthesis and fungicidal activity of novel strobilurin analogues containing substituted N-phenylpyrimidin-2-amines.

A series of novel compounds (5-8) was designed and synthesized by integrating the active pharmacophore of the N-phenylpyrimidin-2-amine fungicide with the structure of strobilurin fungicide. The rationale of this approach was to determine if these new compounds exhibit unique biological activity (selectivity and potency) compared with the commercial standards. The title compounds were prepared from 2-(phenylamino)pyrimidin-4-ols (3) by treatment with one equivalent of intermediates (4) containing strobilurin pharmacophores. 2-(Phenylamino)pyrimidin-4-ols (3) were in turn prepared from phenylguanidines (1) and substituted beta-ketoesters (2). Biological activities evaluated in the greenhouse indicated that compounds 5a, 6a and 7a have good fungicidal activity at 25 mg/L, comparable with that of the commercial standards, cyprodinil and azoxystrobin.

Design, synthesis and biological activity of new strobilurin derivatives with a 1H-pyrazol-5-oxy side chain.

A series of new strobilurin derivatives with a substituted pyrazole side chain (5 and 6) were designed and synthesized. The new derivatives were synthesized from substituted phenones as starting material via esterification, cyclization and condensation reactions. All compounds were identified by 1H NMR and IR spectral and elemental analyses. Preliminary biological evaluation showed that some of the compounds had good fungicidal activity against cucumber downy mildew (CDM) and wheat powdery mildew (WPM) at 6.25 and 1.56 mg L(-1), respectively. Some of the compounds showed insecticidal activity against armyworm (AW), green peach aphid (GPA) and culex mosquitoes at 600 mg L(-1).