Huichao Li

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.

The discovery of SYP-10913 and SYP-11277: novel strobilurin acaricides

BACKGROUND As previously reported, methyl (E)-2-[2-(2-phenylamino-6-trifluoromethylpyrimidin-4-yloxymethyl)phenyl]-3-methoxyacrylate has proven to be a new lead with highly acaricidal activity. Following on from this, in an effort to discover new strobilurin analogues with improved activity, a series of substituted pyrimidines were synthesised and bioassayed. RESULTS All compounds were characterised by (1) H NMR, IR, MS and elemental analysis. Preliminary bioassays demonstrated that some of the title compounds exhibited notable control of Tetranychus cinnabarinus (Boisd.) at 1.25 mg L(-1) . The relationship between structure and acaricidal activity is discussed. CONCLUSION Two compounds of particular interest, 6j (SYP-10913) and 6k (SYP-11277), exhibited potent acaricidal activity. The acaricidal potencies of these analogues are higher than that of fluacrypyrim in greenhouse applications, and are comparable with those of commercial acaricides such as spirodiclofen and propargite in field trials.

Synthesis of novel strobilurin–pyrimidine derivatives and their antiproliferative activity against human cancer cell lines

A series of new strobilurin-pyrimidine analogs were designed and synthesized based on the structures of our previously discovered antiproliferative compounds I and II. Biological evaluation with two human cancer cell lines (A549 and HL60) showed that most of these compounds possessed moderate to potent antiproliferative activity. Two potent candidates (8f, IC50=2.2 nM and 11d, IC50=3.4 nM) were identified with nanomolar activity against leukemia cancer cell line HL60 for further development. This activity represents a 1000- to 2500-fold improvement compared to the parent compounds I and II and is 20- to 30-fold better than the chemotherapy drug, doxorubicin. The present work provides strong incentive for further development of these strobilurin-pyrimidine analogs as potential antitumor agents for the treatment of leukemia.

Design, synthesis and structure–activity relationship of novel diphenylamine derivatives

Diphenylamine derivatives have been reported with good fungicidal, insecticidal, acaricidal, rodenticidal and/or herbicidal activities. To find new lead compound of this kind, a series of novel diphenylamine derivatives were designed and synthesized by the approach of Intermediate Derivatization Methods. All compounds were identified by (1)H NMR and elemental analysis. Bioassays demonstrated that some compounds substituted at 2,4,6-positions or 2,4,5-positions of phenyl ring B exhibited excellent fungicidal activities. The optimal compounds P30 and P33 showed 80% and 85% control respectively against cucumber downy mildew at 12.5mgL(-1), both 100% control against rice blast at 0.3mgL(-1) and both 100% control against cucumber gray mold at 0.9mgL(-1). The relationship between structure and fungicidal activities was discussed as well.

N-Phenyl heteroarylamine analogues of fluazinam using the intermediate derivatization methods approach

AbstractTwenty-one N-phenyl heteroarylamine analogues of fluazinam 3a–3u were prepared via nucleophilic substitution reaction of 2,6-dichloro-3,5-dinitrotoluene with heteroarylamines using the intermediate derivatization method. 2,6-Dichloro-3,5-dinitrotoluene, the key intermediate, was synthesized by nitration of 2,6-dichlorotoluene. The synthesized compounds were identified by 1H NMR, 13C NMR, MS and elemental analyses. Preliminary bioassays indicated that most of the compounds showed good fungicidal activity against rice blast. The activity of 3p was equal to that of fluazinam. The relationship between molecular structure and biological activity suggested that introduction of electron-withdrawing groups in the pyridine ring was important for optimizing fungicidal activity against rice blast. Graphical AbstractThe key intermediate 2,6-dichloro-3,5-dinitrotoluene was prepared starting from 2,6-dichlorotoluene, novel N-Phenyl heteroarylamine Analogues of Fluazinam were designed and synthesized via intermediate derivatization method further. The bioassays showed compound 3p exhibited excellent activity against RB (100%) at 0.1 mg/L, equal to fluazinam.

Synthesis and biological activity of benzoylcyclohexanedione herbicide SYP-9121

Benzoylcyclohexanedione herbicides work by inhibiting 4-hydroxyphenylpyruvate dioxygenase which was the last new target site introduced for herbicides. In an attempt to find new 4-hydroxyphenylpyruvate dioxygenase inhibitors with high efficacy and selectivity, a novel benzoylcyclohexanedione compound SYP-9121 was synthesized and studied in greenhouse and field. In the greenhouse, SYP-9121 showed broad spectrum herbicidal activity and good safety to maize. Its control of barnyard grass, crabgrass, redroot pigweed, purslane, dayflower and night shade was equivalent to that of the commercial herbicide mesotrione. Three field trials in summer maize showed that SYP-9121 could efficiently control both grass and broadleaf weeds with good selectivity. Herbicidal activity of SYP-9121 was comparable to that of mesotrione.