Synthesis and Insecticidal Activity of 3,5-Dimethylbenzoyl Moiety Modified Analogues of N-tert-Butyl-N'-(4-ethylbenzoyl)- 35-d imeth ylbenzohydrazide

20-Hydroxyecdysone (20E) is a major insect hormone that regulates insect metamorphosis and development.' Recently, a new class of compounds has been traced to the 20E agonists that initiate a precocious and incomplete molt. A class of N'-benzoyl-N tert-butylbenzohydrazide (BTBH) analogues have been developed for use as new generation insect growth regulators (IGRs)z-4) that mimic the action of 20E (Fig. 1). Among the BTBH analogues, N-tert-butyl-N'-(4-ethylbenzoyl)-3,5dimethylbenzohydrazide (RH-5992; tebufenozide) is the first commercialized non-steroidal ecdysone agonist that is specific to insects and scarcely toxic to vertebrates.5 To develop novel insecticides, we focused on the clear structural difference between 20E and BTBH, and hypothesized that new BTBH derivatives with structural similarities to 20E would have stronger insecticidal activity. The molting activity of ecdysone is closely dependent on its structure. The C20-C27 side chain plays a particularly important role in the activity. For example, rubrosterone, which does not have this side chain, shows very weak molting activity. Similarly, 22-deoxy-20hydroxyecdysone and 22-iso-20-hydroxyecdysone show very weak activity and no activity, respectively (Fig.1).6) Figure 2 is a hypothetical superimpositional model of the two compounds. According to this simple model, the side chain of 20E is superimposed on the 3-methyl group (or 5-methyl group) of the 3,5-dimethylphenyl moiety (B-ring). For a better fit onto the 20E template, we changed the 3,5-dimethylphenyl part to benzene-ringreduced derivatives, 3-alkoxymethylphenyl derivatives, a 3-hydroxymethyphenyl derivative, 3-halomethylphenyl derivatives, a 3-formylphenyl derivative, a 3-vinylphenyl derivative and heterocyclic derivatives (Fig. 2). In this paper we describe the preparation of fourteen new B-ring-modified RH-5992 analogues (1-14) and also their insecticidal activity against the common cutworm (Spodoptera litura).