Synthesis and Insecticidal Activity of New Deoxypodophyllotoxin-Based Phenazine Analogues against Mythimna separata Walker

In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, a series of new deoxypodophyllotoxin-based phenazine analogues modified in their E-ring were prepared, and their structures were well characterized by H-1 NMR, HRMS, ESI-MS, IR, optical rotation, and mp. The absolute steric configuration of one key isomer was unambiguously confirmed by X-ray crystallography. Their insecticidal activity was examined against the pre-third-instar larvae of oriental armyworm, Mythimna separata (Walker) in vivo at the concentration of 1 mg/mL. All derivatives showed delayed insecticidal activity. Especially compound 9i, containing p-methoxybenzoylamnio at the C-9' position of deoxypodophyllotoxin-based phenazine fragment, exhibited the most promising insecticidal activity with the final mortality rate of 72.4%. According to the symptoms of the tested M. separata, the derivatives likely displayed an antimolting hormone effect. In addition, preliminary structure-activity relationships were observed. These suggested that the proper length of the side chain of alkylacylamino might be important for their insecticidal activity, and introduction of the acylamino groups at the C-9' position of deoxypodophyllotoxin-based phenazine fragment usually afforded more potent compounds than those containing the same ones at the C-10' position. This will pave the way for further design, structural modification, and development of deoxypodophyllotoxin-based derivatives as insecticidal agents.