Design, Synthesis, and Fungicidal Activities of Novel Piperidyl Thiazole Derivatives Containing Oxime Ether or Oxime Ester Moieties

Abstract

To explore the influence of the positions of the two nitrogen atoms on the thiazole ring and the isoxazoline ring on the activity, a series of novel piperidyl thiazole derivatives containing oxime ether and oxime ester moieties with two nitrogen atoms on the same or opposite sides have been designed, synthesized, and first evaluated for their fungicidal activities against Phytophthora capsici in vitro. The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici, among which oxime ether compound 11b shows the highest fungicidal activity in vitro (EC50 = 0.0104 μg/mL) which is higher than dimethomorph (EC50 = 0.1148 μg/mL) and diacetylenyl amide (EC50 = 0.040 μg/mL). Compared with oxime ether compounds (the two nitrogen atoms are on the opposite sides), the activities of oxime ester compounds were significantly reduced. It is different from the commercial fungicide fluoxapiprolin, and the activities of the compounds with the two nitrogen atoms on the same side were significantly reduced compared to the compounds with the two nitrogen atoms on the opposite sides. Moreover, compounds 11b, 11d, 11e, and 11g showed moderate to good antifungal activities in vivo against Phytophthora capsici, Pseudoperonospora cubensis, and Phytophthora infestans. Scanning electron microscopy of compound 11b on the hyphae morphology showed that compound 11b might cause mycelial abnormalities of P. capsici.

Design, synthesis, and fungicidal activities of novel ethylenediamine bridged thiazole derivatives containing oxime ether or oxime ester moieties

“…Each bioassay was repeated three times at 25 ± 1 C. Activity results were estimated according to a percentage scale of 0-100 (0, no activity; 100, total kill). The fungicidal activities of the synthesized compounds were tested using previously reported methods [10]. The results are presented as means ± standard errors.…”

“…The modification of piperidine ring has important effect on the activity. In our previous work, we connected the thiazole ring and the isoxazoline ring with two carbon atoms and opened the isoxazoline ring, designed and synthesized oxime ether and oxime ester analogs with two nitrogen atoms on the same or opposite sides, it was found that these activities of compounds with the nitrogen of oxime ether and thiazolium on the opposite side were generally superior to that on the same side [10].…”

Advances in the green synthesis and agrichemical applications of oxathiapiprolin derivatives

“…The connected thiazole and isoxazoline rings existed in the oxathiapiprolin molecule are heteroatom-rich fragments bearing two nitrogen atoms positioned either at the same or opposite conformations. In 2021, Bian et al (2021) revealed that the position of the two nitrogen atoms has significant influence on the bioactivity through the biological activity screening in vitro of novel piperidyl thiazole derivatives, containing oxime ether and oxime ester derivatives ( Figure 3B ). The bioassay results showed that the target compounds possessed moderate to good fungicidal activities against P. capsici .…”

Structural Modification of Saccharin Containing 2‐Aminothiazole As Potential Fungicidal Agents

“…[16] Recently, some researchers took advantage of hybridization strategy that active thiazole segment was spliced with other pharmacophore (eg. Piperidine [ , pyrazole, quinazoline, and alkaloid) [17][18][19][20][21] to design novel compounds, and further indeed discovered several potential molecules with fungicidal activities.…”