title: Synthesis of novel 4α-(acyloxy)-2'(2',6')-(di)halogenopodophyllotoxin derivatives as insecticidal agents.
abstract: In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, we have prepared three series of novel 4α-(acyloxy)-2'(2',6')-(di)halogenopodophyllotoxin derivatives modified in the C and E rings of podophyllotoxin, which is a naturally occurring aryltetralin lignan isolated from the roots and rhizomes of Podophyllum hexandrum . Their structures were well characterized by (1)H NMR, HRMS, ESI-MS, optical rotation, and mp. The stereochemical configurations of compounds 5s, 6b, 6d, and 7q were unambiguously confirmed by single-crystal X-ray diffraction. Their insecticidal activity was evaluated against the pre-third-instar larvae of oriental armyworm, Mythimna separata Walker, in vivo at a concentration of 1 mg/mL. These derivatives likely displayed the antimolting hormone effect. Among all the derivatives, especially compounds 5a, 5n, 7f, 7n, and 7w exhibited the most potent insecticidal activity with final mortality rates of 70% or so. This suggested that a chlorine or bromine atom introduced at the C2' or C2' and C6' positions on the E ring of podophyllotoxin was necessary for obtaining the potent compounds. This will pave the way for further design, structural modification, and development of podophyllotoxin derivatives as insecticidal agents.
authors.affiliation: Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F University, Yangling 712100, Shaanxi Province, People's Republic of China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Che
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zhi
authors.forename: Lingling
authors.initials: L
authors.lastname: Fan
authors.forename: Xiaojun
authors.initials: X
authors.lastname: Yao
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D054879:Halogenation; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D007814:Larva / Q000187:drug effects / Q000254:growth & development; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects / Q000254:growth & development; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D014961:X-Ray Diffraction
chemical_list: D007306:Insecticides; D011034:Podophyllotoxin