Novel Isoxazolylpyrimidine Derivatives: Design, Synthesis, Antifungal Activity and In‐Silico Studies

Abstract The advancement of environmentally friendly chemical synthesis in both academic and corporate research has recently taken on enormous relevance. Pesticides are substances, either chemical or biological, that are used to get rid of or lessen the impact of pests. To control the fungi in crops a new set of isoxazolylpyrimidine derivatives were planned, synthesized, and characterized. The compounds indicated were synthesized in high yields, and their structures were determined using elemental analysis, 1 H NMR, 13 C NMR, and LCMS. HPLC was used to assess the purity of the synthesized molecules, and the purity of some compounds were found to be >98 % a/a while a couple were found to be >95 % a/a. The synthesized compounds were assessed for their antifungal activity. Among these, compounds 5d , 5h , and 5l exhibit substantial antifungal action and considerably suppress the growth of Rhizoctonia solani, Sclerotium rolfsii, and Macrophominaphaseolina. Macrophominaphaseolina inhibition percentages were 77.60 , 70.49 , 69.03 , Sclerotium rolfsii inhibition percentages were 78.73 , 74.03 , 68.44 , and Rhizoctonia solani inhibition percentages were 81.77 , 76.29 , and 71.01 for compounds 5 d , 5 h and 5 l respectively. The plausible mechanism of fungal inhibitory activities of rationally designed isoxazolyl pyrimidine derivatives is attributed to the blocking of the oxygen activation of HEME iron in membrane‐bound 14α‐demethylase. The presence of pyrimidine unit in designed materials is a vital factor for inducing antifungal activities, which was further corroborated through the density functional theory (DFT),molecular docking studies and molecular dynamics simulation studies.