Design and synthesis of 5,6‐dihydro‐4H‐1,3,4‐oxadiazines as potential octopaminergic insecticides

Abstract

A novel class of insecticides, the dihydrooxadiazines, was proposed following the use of molecular modelling techniques. These compounds represent conformationally restricted analogues of octopamine. Eight dihydrooxadiazines were synthesized and evaluated for useful insecticidal properties. Several of these compounds demonstrated activity against rice planthoppers, mite eggs, and tobacco budworm eggs.

Preparation of Novel Hexythiazox Analogues

“…The oxazolidine and thiazolidine derivatives (6aÈd) were then readily converted into the corresponding hexythiazox analogues (1bÈg and 10a, b) by treatment with cyclohexyl isocyanate (8) or phenyl isocyanate (9) (Fig. 3).…”

The crystal structure of 2-(4-bromophenyl)-4-(2-fluoroethyl)-5,6-dihydro-4H-1,3,4-oxadiazine hydrochloride, an octopaminergic insecticide/miticide

“…based on these atoms was 0.1 A. The two functionalities deemed to be essential to octopaminergic pesticidal action (14), a phenyl ring and a suitably situated amino group, appear to be conserved in 4. A similar comparison between the octopaminergic pesticide, chlordimeform 2, and octopamine 1 also resulted in identification of common structural features (26).…”

“…Recently, dihydrooxadiazines were identified (14,15) as novel octopaminergic insecticides. They were shown to be octopamine agonists in the two-spotted spider mite, Tetranychus urticae (16), and in the American cockroach, Can For personal use only.…”

“…From the chemistry point of view, it is interesting to speculate why 4 should behave as an octopamine agonist when the two compounds, 1 and 4, do not obviously resemble one another. Through molecular modelling studies, structural similarities between dihydrooxadiazines and octopamine have been shown (14). To validate the molecular modelling studies, we required a precise structure of a highly active dihydrooxadiazine compound.…”

Substituent‐dependent, positive and negative modulation of Bombyx mori adenylate cyclase by synthetic octopamine/tyramine analogues

“…The activation of the OCT 1 receptor elevates the intracellular level of Ca 2+ , while the activa-tion of the other OCT receptors leads to an increase in the intracellular level of the second messenger cAMP by activating adenylate cyclase (Evans, 1981;Harmar and Horn, 1977;Nathanson, 1979;Nathanson and Greengard, 1973). The adenylate cyclase-coupled OCT receptors have been considered to be a potential target of insectistatic or insecticidal compounds (Dekeyser et al, 1993;Kadir and Knowles, 1991;Nathanson and Hunnicutt, 1981). The research to date has found that a variety of compounds act as agonists and antagonists of OCT 2 and OCT 3 receptors (Roeder, 1999).…”