Studies on Biologically Active Heterocyclic Compounds

Abstract

On the basis of the natural product models and biochemical designs, attempts were made to find leads for the development of new pesticide chemicals. Antilipidemic agents of several different chemical classes and cis-7-chloro-3a, 8b-dihydro-3a-methylfuro[3, 4-b]benzofuran-3 (1H)-one, which inhibited HMG-CoA reductase activity in rats in vivo, showed ovicidal activity against the eggs of azuki bean weevils, Callosobruchus chinensis, but failed to produce clear anti-juvenile hormone (JH) activity. A number of imidazole compounds possessing a JH-like terpene chain, designed to be potential inhibitors of JH biosynthesis, were synthesized and bioassayed on the silkworm, Bombyx mori larvae. New compounds, 1-geranyl-5-phenylimidazole (A-1) and the 1-citronellyl analog (A-2), showed remarkable anti-JH activity. When treated to the third instar larvae, miniature pupae were formed after molting to the fourth instar larvae. The fifth instars were also omitted by treatment of the fourth instar larvae. The presence of a phenyl group at the 5 position of the imidazole ring is essential for anti-JH activity. The introduction of a methoxy group in the 7 position of the terpene chain of A-1 and A-2 eliminated or decreased the activity. The anti-JH effects of A-1 and A-2 on B. mori larvae were completely blocked by simultaneous application of such a JH mimic as methoprene. Benzimidazoles having a terpenoid moiety, 1-(3, 7-dimethyl-7-methoxy-2-octenyl)-2-methylbenzimidazole (B-1) and the 7-ethoxy analog (B-2), showed high insecticidal activity against houseflies and green rice leafhoppers, Nephotettix cinticeps. They inhibited also larval molting of B. mori at low doses when applied topically to the larvae 1-2 days before erdysis. 8-Isopropyl-6-oxabicyclo[3.2.1]octan-7-one (trans-lactone) with a partial skeleton of picrotoxinin, which is an antagonist of γ-aminobutyric acid, and some related lactones were synthesized and their insecticidal activities were assayed on houseflies. In the insecticidal activity of the lactone compounds the configuration of the isopropyl group at C₈-position played an important role. Thus trans-lactone had the highest activity. Ninety s-triazine derivatives were prepared by the reaction of amino acids and peptides with substituted biguanides and bioassayed on plant growth. Among the tested compounds the s-triazine derived from leucylleucine exhibited the highest growth inhibitory activity on rice.