Synthesis, antifungal activity and 3D-QSAR study of novel nopol-based 1,3,4-thiadiazole–thioether compounds

• Published in: Research on chemical intermediates 2021-10, Vol.47 (10), p.4029-4049
• Main Authors: Wang, Xiu, Duan, Wen-Gui, Lin, Gui-Shan, Chen, Ming, Lei, Fu-Hou
• Format: Article
• Language: English
• Subjects: Catalysis; Chemical analysis; Chemistry; Chemistry and Materials Science; Fungicides; Fusarium oxysporum; Inorganic Chemistry; NMR; Nuclear magnetic resonance; Physical Chemistry; Thiadiazoles; Three dimensional analysis
• ISSN: 0922-6168; 1568-5675
• DOI: 10.1007/s11164-021-04510-x

A series of novel nopol derivatives containing 1,3,4-thiadiazole–thioether moiety were synthesized from β -pinene, which is a natural, abundant and renewable biomass resource. Their structures were characterized by FT-IR, 1 H NMR, 13 C NMR, ESI–MS and elemental analysis. In vitro antifungal activity of the target compounds was preliminarily evaluated against eight tested plant pathogens, including Fusarium oxysporum f. sp. cucumerinum , Cercospora arachidicola , Physalospora piricola , Alternaria solani , Gibberella zeae , Rhizoeotnia solani , Bipolaris maydis and Colleterichum orbicalare . The bioassay results revealed that, at the concentration of 50 μg/mL, all the target compounds showed certain inhibition activity against the eight tested fungi. Compounds 5f (R =  m –OCH 3 ), 5i (R =  m –F) and 5r (R =  m –I) had excellent inhibition rates of 77.8%, 88.9% and 77.8%, respectively, against P. piricola , showing much better antifungal activity than that of the positive control chlorothalonil. Meanwhile, compound 5 m (R =  p –Cl) displayed antifungal activity of 80.7% against R. solani . Furthermore, the analysis of three-dimensional quantitative structure–activity relationship (3D-QSAR) was performed for the relationship between the structures of the target compounds and their antifungal activity against P. piricola by CoMFA method. A reasonable CoMFA model ( n  = 6; q 2  = 0.597; r 2  = 0.985) was established.