The Synthesis and Fungicidal Activity of 2-Substituted 1-Azol-1-ylmethyl-6-arylidenecyclohexanols

Abstract

: A number of substituted 2,2-dimethyl-6-arylidene-1-triazol-1-ylmethylcyclohexanols and 2,2-dimethyl-6-arylidene-1-imidazol-1-ylmethylcyclohexanols were prepared from 2-methylcyclohexanone in four steps : ClaisenÈ Schmidt condensation with substituted benzaldehydes, methylation of the resulting 2-methyl-6-benzylidenecyclohexanones, conversion to the oxiranes by interaction with dimethylsulfonium methylide and reaction of the oxiranes with triazole or imidazole. The compounds obtained were tested for antifungal activity against Ðve phytopathogenic fungi of di †erent taxonomic classes. values EC 50 were determined for all compounds. StructureÈactivity relationships are discussed in broad terms. Some of triazolymethyl-substituted cyclohexanols obtained are more active than triadimenol.

Synthesis, Fungicidal Activity, and Sterol 14α-Demethylase Binding Interaction of 2-Azolyl-3,4-dihydroquinazolines on Penicillium digitatum

“…Among various kinds of fungicides, azoles are the most widely used and studied class of antifungal agents in agricultural usage because of their lower application doses, high selectivity, and reduced undesired environmental impact. , The biochemical site of action of the fungicidal azoles is the cytochrome P450-dependent lanosterol 14α-demethylase (CYP51), encoded by the ERG11 gene in fungal cells . This heme protein binds tetracyclic steroid molecules, inserting one oxygen atom into a CH bond of the C-14 methyl group . Azole antifungal agents inhibit CYP51 by a mechanism in which the heterocyclic nitrogen atom (N3 of imidazole and N4 of triazole) binds to the heme iron atom in the binding site of the enzyme.…”

“…5 This heme protein binds tetracyclic steroid molecules, inserting one oxygen atom into a CH bond of the C-14 methyl group. 6 Azole antifungal agents inhibit CYP51 by a mechanism in which the heterocyclic nitrogen atom (N3 of imidazole and N4 of triazole) binds to the heme iron atom in the binding site of the enzyme. Unfortunately, azoles are fungistatic against yeasts, and the broad usage of these compounds led to the development of resistance, showing the urgent need for new and effective antifungal agents.…”