title: Insight into dihalogenation of E-ring of podophyllotoxins, and their acyloxyation derivatives at the C4 position as insecticidal agents.
abstract: Unexpected sequential E-ring dihalogenation of podophyllotoxin analogues is reported. It demonstrated that a chlorine/bromine atom was prior introduced at the C2' position of podophyllotoxin, and the corresponding free rotation of E-ring around the C1-C1' bond of 2'-chloro or 2'-bromopodophyllotoxin was restricted. When 2'-chloro or 2'-bromopodophyllotoxin reacted with N-chlorosuccinimide (NCS), the chlorine atom was regioselectively introduced at their C6' position on the E-ring. Whereas 2'-chloro or 2'-bromopodophyllotoxin reacted with NBS, the bromine atom was regioselectively introduced at their C5 position on the B-ring. When 2'-chloropodophyllotoxin reacted with different carboxylic acids in the presence of BF3·Et2O, the steric effect of its E-ring for stereoselective synthesis of 4β-acyloxy-2'-chloropodophyllotoxin derivatives was observed. The insecticidal activity of 2'(2',6')-(di)halogen-substituted podophyllotoxin derivatives were evaluated with Mythimna separata Walker.
authors.affiliation: Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F University, Yangling 712100, Shaanxi Province, China; College of Forestry, Henan University of Science and Technology, Luoyang 471003, Henan Province, China.
authors.forename: Zhiping
authors.initials: Z
authors.lastname: Che
authors.forename: Xiang
authors.initials: X
authors.lastname: Yu
authors.forename: Lingling
authors.initials: L
authors.lastname: Fan
authors.forename: Hui
authors.initials: H
authors.lastname: Xu
mesh_terms: D000818:Animals; D002713:Chlorine / Q000737:chemistry; D018360:Crystallography, X-Ray; D054879:Halogenation; D007306:Insecticides / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D008968:Molecular Conformation; D009036:Moths / Q000187:drug effects; D011034:Podophyllotoxin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000633:toxicity; D013237:Stereoisomerism; D013388:Succinimides / Q000737:chemistry
chemical_list: D007306:Insecticides; D013388:Succinimides; C015752:N-chlorosuccinimide; D002713:Chlorine; D011034:Podophyllotoxin
keywords: Botanical insecticide; Halogenation; Insecticidal activity; Mythimna separata Walker; Podophyllotoxin; Structural modification