Ethyl 4-[2-(substituted benzyl)hexyloxy]benzoates: Anti-juvenile hormone agents with juvenile hormone activity

A large number of ethyl [2-(substituted benzyl)hexyloxy]benzoates and related compounds were prepared and their activity to induce precocious metamorphosis was evaluated in larvae of Bombyx mori, which was obviously recognized as a juvenile hormone (JH)-deficiency symptom. Introduction of a methyl, chloro or fluoro substituent at the 2-position on the benzene ring increased the activity in comparison with that of ethyl (2-benzylhexyloxy) benzoate (KF-13) in a dose range of 1-40 μg, however, no consistent dose-response relationship was obtained in these compounds as well as KF-13. The 4-methoxybenzyl analog showed strong precocious metamorphosis-inducing activity at both low and high doses, while introduction of other substituents such as a methyl, chloro, fluoro or ethyl group at the 3- and 4-position on the benzene ring decreased the activity at low doses. The JH activity of synthesized compounds was examined by bioassay using allatectomized 4th instar larvae. In the ethyl [2-(substituted benzyl)hexyloxy]benzoate series, a correlation was observed between JH activity and anti-JH activity; Compounds which induced high percentages of precocious metamorphosis at lower doses had obvious JH activity. Compounds possessing weak precocious metamorphosis-inducing activity showed little JH activity.