Synthesis and structure-activity relationship of a new series of anti-juvenile hormone agents: Alkyl 4-(2-benzylhexyloxy) benzoates and ethyl 4-substituted benzoates

A series of alkyl 4-(2-benzylhexyloxy)benzoates and related compounds were synthesized and investigated for their ability to induce precocious metamorphosis in larvae of Bombyx mori, a clear sign of JH deficiency in the hemolymph of early larval stages. In the alkyl 4-(2-benzylhexyloxy)benzoate series, the methyl and ethyl (KF-13) esters induced precocious metamorphosis at relatively low doses. Replacement of the ester group with an amide, alcohol, oxime, ethyl or 3,4-methylenedioxy group eliminated the activity, indicating that the ester group on the benzene ring is essential for activity. A modification was made between the two benzene rings in KF-13. None of the compounds showed higher activity than KF-13 at low doses. The JH activity of synthesized compounds was assayed using allatectomized 4th instar larvae of B. mori. The aniline analog, which showed stronger precocious metamorphosis-inducing activity than KF-13 at higher doses, had obvious JH activity. The n-propyl ester possessing moderate precocious metamorphosis-inducing activity did not show any JH activity. There was some correlation between the ability of compounds to cause precocious metamorphosis and their JH activity.