Insect metabolism of a phenyl epoxygeranyl ether juvenoid and related compounds

1-(4′-Ethylphenoxy)-3,7-dimethyl-6,7-epoxy-trans-2-octene (the ethyl-epoxide), a potent insect morphogenetic agent, is converted to 6,7-diol and other derivatives in living cockroaches and mealworms. Enzyme preparations of these organisms, and of houseflies and several other insect species, also carry out these hydration and/or oxidation reactions. In addition, housefly microsomes epoxidize the ethyl-epoxide to a diepoxide. The diepoxide and diol are then converted by microsomes to at least six cyclic diols, probably via an epoxy-diol intermediate, the major ones being the cis- and trans-tetrahydrofurandiol derivatives. The metabolites formed by these reactions have little or no morphogenetic activity in Tenebrio assays. Attempts to find potent inhibitors for housefly epoxide hydratases were unsuccessful. The corresponding ethylphenyl geranyl ether is epoxidized by housefly microsomes, forming the more morphogenetically active ethyl-epoxide, but the major reaction is oxidation on the geranyl moiety to an unidentified olefinic carboxylic acid. The chemical modifications needed for improved stability and morphogenetic activity in this juvenoid series depend on the insect species and strain and the relative activities of their enzymes involved in various inactivation pathways.