The Synthesis, Fungicidal Activity, and in Silico Study of Alkoxy Analogues of Natural Precocenes I, II, and III.

This study aimed to synthesize, characterize, and explore the eco-friendly and antifungal potential of precocenes and their derivatives. The organic synthesis of the mono-O-alkyl-2,2-dimethyl 2-1-chromene series, including the natural product precocene I, and the di--alkyl 2,2-dimethyl-2-1-chromene series, including the natural 2-1-chromenes precocenes II and III, was achieved. The synthetic compounds were subjected to spectroscopic analysis, HNMR,CNMR, and mass characterization. The antifungal activity of synthesized precocenes I, II, and III, as well as their synthetic intermediates, was evaluated by the poison food technique. Precocene II (EC 106.8 µg × mL and 4.94 µg mL), and its regioisomers (EC 97.18 µg × mL and 35.30 µg × mL) and (EC 170.58 × µg mL), exhibited strong fungitoxic activity against and . Some of the novel chromenes, and , which had never been evaluated before, yielded stronger fungitoxic effects. Finally, docking simulations for compounds with promising fungitoxic activity were subjected to structure-activity relationship analyses against the polygalactouronases and voltage-dependent anion channels. Conclusively, precocenes and their regioisomers demonstrated promising fungitoxic activity; such compounds can be subjected to minor structural modifications to yield promising and novel fungicides.