Dongyan Yang

Synthesis, Antifungal Activity and Structure-Activity Relationships of Novel 3-(Difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic Acid Amides

A series of novel 3-(difluoromethyl)-1-methyl-1H-pyrazole-4-carboxylic acid amides were synthesized and their activities were tested against seven phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to excellent activities. Among them N-(2-(5-bromo-1H-indazol-1-yl)phenyl)-3-(difluoro-methyl)-1-methyl-1H-pyrazole-4-carboxamide (9m) exhibited higher antifungal activity against the seven phytopathogenic fungi than boscalid. Topomer CoMFA was employed to develop a three-dimensional quantitative structure-activity relationship model for the compounds. In molecular docking, the carbonyl oxygen atom of 9m could form hydrogen bonds towards the hydroxyl of TYR58 and TRP173 on SDH.

Synthesis, antifungal activity and QSAR of some novel carboxylic acid amides.

A series of novel aromatic carboxylic acid amides were synthesized and tested for their activities against six phytopathogenic fungi by an in vitro mycelia growth inhibition assay. Most of them displayed moderate to good activity. Among them N-(2-(1H-indazol-1-yl)phenyl)-2-(trifluoromethyl)benzamide (3c) exhibited the highest antifungal activity against Pythium aphanidermatum (EC50 = 16.75 µg/mL) and Rhizoctonia solani (EC50 = 19.19 µg/mL), compared to the reference compound boscalid with EC50 values of 10.68 and 14.47 µg/mL, respectively. Comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) were employed to develop a three-dimensional quantitative structure-activity relationship model for the activity of the compounds. In the molecular docking, a fluorine atom and the carbonyl oxygen atom of 3c formed hydrogen bonds toward the hydroxyl hydrogens of TYR58 and TRP173.

Synthesis, resolution and biological evaluation of cyclopropyl analogs of abscisic acid

cis-2,3-Cyclopropanated abscisic acid (cis-CpABA) has high photostability and good ABA-like activity. To further investigate its activity and action mechanism, 2S,3S-2,3-cyclopropanated ABA (3a) and 2R,3R-2,3-cyclopropanated ABA (3b) were synthesized. Bioassay showed that 3a displayed higher inhibitory activity in germination than that of 3b and ABA at the concentration of 3.0 μM, but 3a and 3b had much weaker inhibitory activity in inhibition seedling growth compared to ABA. The study of photostability revealed that 3a and 3b showed high stability under UV light exposure, which were 4 times and 3 times greater than (±)-ABA, respectively. Action mechanism study showed that 3a presented higher inhibition on phosphatase activity of HAB1 than 3b, although they all inferior to ABA. Molecular docking studies of 3a, 3b and ABA receptor PYL10 were agreement with the bioassay data and confirmed the importance of the configuration of the 2,3-cyclopropyl ABA analogs for their bioactivity in somewhat. This study provides a new approach for the design of ABA analogs, and the results validated structure-based design for this target class.

Design, Synthesis and Insecticidal Activity of Novel Hydrocarbylidene Nitrohydrazinecarboximidamides

BACKGROUND Neonicotinoids, among the most important pesticides in recent decades, have played pivotal roles in controlling agricultural pests. However, the toxicity to some environmentally beneficial insects is a cause of concern. The development of novel insecticides safer to these insects is increasingly urgent. RESULTS A novel series of hydrocarbylidene nitrohydrazinecarboximidamides were designed and synthesised, starting from S-methylisothiourea sulphate. Preliminary bioassays showed that the target molecules exhibited good activities against Lipaphis erysimi (turnip aphid) and Myzus persicae. As shown by initial insecticidal activity data, most of the target compounds had moderate to excellent activities at a concentration of 600 mg L-1 against L. erysimi, and the lethal rate of most compounds exceeded 90%. They were also highly effective against M. persicae. Some of them have shown excellent insecticidal activities, for example, the LC50 values of compounds Ie-02 to Ie-07 were found to be 3.8, 3.0, 2.5, 3.1, 4.1 and 4.0 mg L-1 respectively. CONCLUSION Structure-activity relationship analysis indicated that a suitable flexible alkyl chain at the imine point and a Cl-substituted pyridine ring are the most crucial factors affecting the activity.

Synthesis, insecticidal and fungicidal activities of methyl 2-(methoxyimino)-2-(2-((1-(N′-nitrocarbamimidoyl)-2-hydrocarbylidenehydrazinyl)methyl)phenyl)acetates

N′-Nitro-2-hydrocarbylidenehydrazinecarboximidamides and methoxyacrylates are two types of important agrochemicals. By combining their key fragments into one framework, a series of the title compounds was designed and synthesized. Some of these compounds have shown excellent insecticidal activities for aphides, for example, the LC50 values of compounds 6-06, 6-11 and 6-19 against M. perslcae and H. amygdale were found to be 1.9/14.4, 13.4/1.5 and 0.3/38.4 mg L−1 respectively. They were also effective against the mycelium growth of B. cinerea in vitro. Compound 6-04 could control (∼100%) cucumber anthrax and rice blast at 100 mg L−1 in vivo, and inhibit the spore germination (∼100%) of vegetable gray mold at 6.25 mg L−1. These compounds could be considered as potential insecticidal or fungicidal candidates for crop protection. The results of structure–activity relationship (SAR) studies are discussed.

A highly efficient regioselective addition of acetylides to enediones based on steric effects.

A simple and efficient strategy for the synthesis of 1-ethynylcyclohex-2-enol derivatives was developed utilizing regioselective addition of acetylides to enediones based on steric effects. Further investigation of the substrate scope of enediones indicated that all the addition reactions ocurred in good yield.

Design, synthesis, and insecticidal activity of novel 1-alkoxy-2-nitroguanidines

In searching for new insecticidal lead compounds, a series of novel 1-alkoxy-2-nitroguanidine, guadipyr analogues bearing alkoxy groups were designed, synthesized and confirmed by 1H NMR, 13C NMR, high-resolution mass spectrometry and X-ray diffraction. The primary bioassays showed that most of these compounds exhibited moderate to good insecticidal activity against Myzus persicae and Aphis gossypii. Especially, the precise insecticidal assay showed that compounds 4-02, 4-07 and 4-08 displayed excellent in vitro activity with IC50 values lower than 10 μg mL−1 to M. persicae which is comparable to guadipyr. On the other hand, the toxicity of compound 4-07 and guadipyr against honey bees was much lower than imidacloprid. The results indicated that the flexible chain on the nitrogen atom was the most crucial factor on honey bee toxicity, which existed in both neonicotinoids and guadipyr series.

Synthesis and Biological Activity of 2′,3′-iso-Aryl-abscisic Acid Analogs

2′,3′-iso-Benzoabscisic acid (iso-PhABA), an excellent selective abscisic acid (ABA) analog, was developed in our previous work. In order to find its more structure-activity information, some structural modifications were completed in this paper, including the substitution of phenyl ring and replacing the ring with heterocycles. Thus, 16 novel analogs of iso-PhABA were synthesized and screened with three bioassays, Arabidopsis and lettuce seed germination and rice seedling elongation. Some of them, i.e., 2′,3′-iso-pyridoabscisic acid (iso-PyABA) and 2′,3′-iso-franoabscisic acid (iso-FrABA), displayed good bioactivities that closed to iso-PhABA and natural (+)-ABA. Some others, for instance, substituted-iso-PhABA, exhibited certain selectivity to different physiological process when compared to iso-PhABA or (+)-ABA. These analogs not only provided new candidates of ABA-like synthetic plant growth regulators (PGRs) for practical application, but also new potential selective agonist/antagonist for probing the specific function of ABA receptors.