Juvenile hormone activity of optically active ethyl 4-(2-benzylalkyloxy)benzoates inducing precocious metamorphosis

Abstract

A series of ethyl 4-(2-benzylalkyloxy)benzoates possessing precocious metamorphosis-inducing activity showed juvenile hormone (JH) activity when topically applied to allatectomized 4th instar larvae of Bombyx mori. Hexyl (KF-13) and heptyl analogs, which induced precocious metamorphosis at low doses, had relatively high JH activity. In both compounds, (S )-enantiomers were more active than (R)-enantiomers. A correlation was observed between JH activity and anti-JH activity in the ethyl 4-(2-benzylalkyloxy)benzoate series. Replacement of the 4-ethoxycarbonyl group with a 4-ethyl or 3,4-methylenedioxy group in KF-13 eliminated both JH and anti-JH activity.

An anti-juvenile hormone agent, ethyl 4-(2-benzylhexyloxy)benzoate, inhibits juvenile hormone synthesis through the suppression of the transcription of juvenile hormone biosynthetic enzymes in the corpora allata in Bombyx mori

“…The compound shows strong anti-JH activity in the range of the concentration of 0.1-1.0 mg/larva when it was applied to day 1 3rd instar larvae, but it acquires JH-like activity in higher dosages (1e10 mg/larva; assayed using allatectomized 4th instar larvae) (Furuta et al, 2007;Fujita et al, 2008). The maximum induction of precocious metamorphosis was caused by application of 1 mg KF-13S (96e100%) to 3rd instar larvae; the same concentration applied to 4th instar larvae induced this response in only 10% of the treated insects.…”

“…The maximum induction of precocious metamorphosis was caused by application of 1 mg KF-13S (96e100%) to 3rd instar larvae; the same concentration applied to 4th instar larvae induced this response in only 10% of the treated insects. Since 1 mg KF-13S has both anti-JH and JH-like activities (Furuta et al, 2007;Fujita et al, 2008), the induction by this dose of precocious metamorphosis of 3rd instar larvae, after their successful ecdysis to the 4th instar larvae, can be explained as follows: although the applied KF-13S, might have had overwhelming JH-like activity at the time of application, the compound's anti-JH activity becomes stronger with the degradation of the compound and its reduced concentration in the insect due to continued growth of the larvae, so that by the 4th instar, anti-JH activity overcomes JH-like activity. This hypothesis is also supported by the results in the 4th instar larvae that 1 mg KF-13S induced precocious pupation in 10% of the treated larvae, but none responded in this way to the application of 10 mg (Furuta et al, 2007).…”

“…1) derived from ETB showed the same activity as ETB in B. mori, but one enantiomer, ethyl 4-[(S)-2-benzylhexyloxy]benzoate (KF-13S), had much stronger anti-JH action than the corresponding (R)-enantiomer, ethyl 4-[(R)-2-benzylhexyloxy]benzoate (KF-13R) and ETB itself; thus, 0.1e1 mg KF-13S caused precocious metamorphosis of the 3rd instar larvae, whereas a high dose of KF-13R (10e40 mg/ larva) was necessary to cause precocious pupation (Furuta et al, 2007). As found for ETB, higher doses of both enantiomers of KF-13 showed JH-like activity (Fujita et al, 2008). Application of a JH analog, methoprene, rescued the anti-JH action of both ETB (Staal, 1977;Kiguchi et al, 1984) and KF-13 (Furuta et al, 2007), suggesting that these compounds prevent JH synthesis, although there remains the possibility that they can also act simultaneously as antagonists of JH.…”

Physiological Activities of Anti-Juvenile Hormone Agents Against Insects and Their Role For Devising Fourth Generation Insecticides: A Comprehensive Review

“…Some KF compounds had been prepared and bioassyed against B. mori. KF-13S and KF-13 induced precocious metamorphosis in B. mori (Furuta et al, 2007;Fujita et al, 2008).…”

Synthesis and anti-juvenile hormone activity of ethyl 4-[(6-substituted 2,2-dimethyl-2H-chromen-7-yl)methoxy]benzoates

“…The JH activity of compounds was evaluated by molting into normal 5th instars when topically applied to allatectomized 24-hr-old 4th instar larvae. 8) …”