Synthesis of Novel 4‐Acyloxy‐2′‐Bromo‐6′‐Chloropodophyllotoxin Derivatives Displaying Significant Insecticidal Activity Against Mythimna Separata

Abstract

AbstractIn order to explore novel natural product‐based insecticidal agent, two important intermediates (2 and 3) and 4‐acyloxy‐2′‐bromo‐6′‐chloropodophyllotoxin derivatives (4 a–f and 5 a–f) were designed and prepared, and their structures were confirmed by 1H‐NMR, 13C NMR, HRMS, ESI‐MS, optical rotation and melting point (mp). The stereochemical configuration of compound 4 b was unambiguously confirmed by single‐crystal X‐ray diffraction. Moreover, we evaluated the insecticidal activity of target compounds 4 a–f and 5 a–f against a serious agricultural pest of Mythimna separata by using the leaf‐dipping method. Among all tested compounds, compounds 4 d, 5 d and 5 f exhibited stronger insecticidal activity with a final mortality rate exceeding 60 %. Especially compound 5 d exhibited the best insecticidal activity, with a final mortality rate of 74.1 %. It has been proven that introducing bromine or chlorine atoms at the C‐2′, C‐2′ and C‐6′ positions of the E ring of podophyllotoxin can produce more potent compounds. In addition, the configuration of the C‐4 position is important for insecticidal activity, and 4β‐configuration is optimal. This will pave the way for further design, structural modification, and development of derivatives of podophyllotoxin as insecticidal agents.