Synthesis and Anti-Juvenile Hormone Activity of Ethyl 4-[2-(6-Methyl-3-pyridyloxy)alkyloxy]benzoates

Abstract

A series of ethyl 4-[2-(6-methyl-3-pyridyloxy)alkyloxy]benzoates was prepared and tested for activity to induce precocious metamorphosis in larvae of the silkworm, Bombyx mori. Of the compounds tested, ethyl 4-[4-methyl-2-(6-methyl-3-pyridyloxy)pentyloxy]benzoate (5) was the most effective when applied to 24 hr-old 3rd instar larvae. There was no significant difference in precocious metamorphosis-inducing activity between 5R(ϩ)-and 5S(Ϫ)-enatiomers. The activity of compound 5 could be fully counteracted by methoprene, a juvenile hormone (JH) agonist, but not by the dietary administration of 20-hydroxyecdysone. When 3rd instar larvae were treated with compound 5, hemolymph JH esterase activity, which is indispensable for the initiation of pupation in normal last instar larvae, was induced during the 4th instar.

Synthesis and anti-juvenile hormone activity of ethyl 4-(2-benzylalkyloxy)benzoates and their enantiomers

“…The introduction of an n-propyl group (4) increased the degree of activity in comparison with that of 3. In contrast to the results found in ethyl 4-[2-(6-methyl-3-pyridyloxy)alkyloxy]benzoate series, 7) isobutyl analog 5 showed lower activity than n-propyl analog 4. The n-butyl group (6) gave a remarkable increase in activity at a low dose of 1 mg, but the activity comparatively decreased by increasing the applied doses.…”

“…Similar results have been obtained in the 4-[2-(6-methyl-3-pyridyloxy)-alkyloxy]benzoate series. 7) As previously described, precocious metamorphosis is well known to be induced by JH deficiency in the larval stage caused by allatectomy or treatment of anti-JH agents 2) ; however, we have found that the precocious metamorphosis-inducing activity of some 1,5-disubstituted imidazoles is completely reversible by the dietary administration of 20-hydroxyecdysone, suggesting that a temporary decline of ecdysteroid titers in the larval hemolymph might also cause precocious metamorphosis. 12) We therefore examined the effects of methoprene, a JH agonist, and 20-hydroxyecdysone on the precocious metamorphosis induced by 6 ( Table 3).…”

“…By modifying the structure of ETB, we have recently found that ethyl 4-[4-methyl-2-(6-methyl-3-pyridyloxy)pentyloxy]-benzoate (1) 7) and ethyl 4-(2-phenoxyhexyloxy)benzoate (2) 8) showed stronger precocious metamorphosis-inducing activity than ETB against B. mori larvae (Fig. 1).…”

Juvenile Hormone Activity of Ethyl 4-(2-Aryloxyhexyloxy)benzoates with Precocious Metamorphosis-Inducing Activity

“…Riddiford et al have reported that ETB acted as a partial antagonist in the Manduca epidermis at the target-tissue level. 7) As previously reported, 3,4) in our bioassay using 24-hr-old 3rd instar larvae of B. mori, ETB at 1 mg induced precocious pupation in only 10% and no activity was observed at higher doses of 10 mg and 40 mg, while compounds 1 and 2 induced precocious metamorphosis even at high doses. ETB clearly acts as a JH agonist to counteract the effect of allatectomy, the induction of precocious metamorphosis, in a dose-dependent manner.…”

Synthesis and biological activity of novel anti-juvenile hormone agents

“…14) In the silkworm, JHE activity in the hemolymph is quite low in 4th-instar larvae and increases in 5th-instar larvae, thereby decreasing the JH titer and inducing metamorphosis. 15) We have found that compound 2 9) and KF-13 16) induce hemolymph JH esterase activity during the 4th instar when applied to 3rd-instar larvae of B. mori. This result supports the concept that the appearance of JHE activity in the hemolymph is indispensable for the initiation of pupation.…”