Anti-juvenile hormone activity of ethyl 4-[(7-substituted 1,4-benzodioxan-6-yl)methyl]benzoates and their effect on the juvenile hormone titer in the hemolymph of the silkworm, Bombyx mori.

A series of ethyl 4-[(7-substituted 1,4-benzodioxan-6-yl)methyl]benzoates was synthesized and evaluated for their anti-juvenile hormone (anti-JH) activities to induce precocious metamorphosis in silkworm (Bombyx mori) larvae. The introduction of bulky alkyloxy substituents on the 7-position on the benzodioxan ring significantly increased activity. Ethyl 4-[(7-benzyloxy-1,4-benzodioxan-6-yl)methyl]benzoate (4c) showed the most potent activity among the test compounds, and its median-effective dose (ED50) value was 41 ng/larva. The JH I, II, and III concentrations in the hemolymph of the 3rd instar larvae treated with compound 4c were determined by ultra-high-performance liquid chromatography/mass spectrometry (UHPLC/MS) after using a simple purification method. Compound 4c clearly decreased the JH I and II titers of 3rd instar larvae within 24 hr after treatment, and prevented JH I spike usually found immediately after 4th instar molting.