Thymol as an Interesting Building Block for Promising Fungicides against .

The semisynthesis of 15 new thymol derivatives was achieved through Williamson synthesis and copper-catalyzed azide-alkyne cycloaddition (CuAAC) approaches. The reaction of CuAAC using the "" strategy, in the presence of an alkynyl thymol derivative and commercial or prepared azides, provided nine thymol derivatives under microwave irradiation. This procedure reduces reaction time and cost. All molecular entities were elucidated by H and C NMR, IR, and HRMS data. These derivatives were evaluated for their fungicidal activity against sp. Among the nine triazolic thymol derivatives obtained, seven of them were found to have moderated antifungal activity. In contrast, naphthoquinone/thymol hybrid ether displayed activity comparable with that of the commercial fungicide thiabendazole. The structure-activity relationship for the most active compound was discussed, and the mode of action was predicted by a possible binding to the fungic ergosterol and interference of osmotic balance of K into the extracellular medium.