Synthesis and fungicidal activity of a series of novel aryloxylepidines

A series of novel (hetero) aryloxylepidine derivatives was devised as hybrid structures of the phenoxyquinoline and phenethoxyquin(az)oline fungicides. Synthesis of these targets required the development of several new routes to derivatised 4-hydroxymethylquinolines, and subsequent coupling with phenols or haloarenes. The aryloxylepidines generally showed moderate broad-spectrum fungicidal activity across several diseases of cereals. Substitution of the quinoline ring with chlorine at the 7- and/or 5-positions gave molecules with high levels of protectant activity against Erysiphe graminis f sp tritici (powdery mildew of wheat), but this did not improve the level of fungicidal activity against other diseases. In vitro activity against mitochondrial electron transport complex I (MET) derived from Ustilago maydis showed that 8-fluorolepidine analogues were moderately active at this target site, while the more fungicidally active 7- and 5,7-substituted compounds were inactive. This indicates that MET is not the primary target of these highly active powdery mildewicides.