Stereoselective synthesis of 2α-Chloropicropodophyllotoxins and insecticidal activity of their esters against oriental armyworm, Mythimna separata walker.
As part of ongoing efforts to discover new natural-product-based insecticidal agents, in the present study, an efficient method for the stereoselective α-chlorination at the C-2 position of 2'(2',6')-(di)halogenopodophyllotoxin derivatives was first developed. Subsequently, a series of novel esters of 2α-chloro-2'(2',6')-(di)halogenopicropodophyllotoxin with modified C, D, and E rings of podophyllotoxin were smoothly obtained. Finally, all of the title compounds were tested against the pre-third-instar larvae of oriental armyworm (Mythimna separata Walker) at 1 mg/mL. It was found that besides their 2'-halogen-substituted E ring, the stereoselective α-chlorination at the C-2 position of 2'(2',6')-(di)halogenopodophyllotoxins was also related to the chlorination reagents. Especially 2α-chloro-4α-(benzoyl)oxy-2'-chloropicropodophyllotoxin (6e) and 2α-chloro-4α-(2-chlorophenylacyl)oxy-2'-bromopicropodophyllotoxin (8f) showed the most potent insecticidal activities, with final mortality rates of >60%. For 4α-(alkylacyl)oxy derivatives of 2α-chloro-2'(2',6')-(di)halogenopicropodophyllotoxin, the effect of the length of their side chain at the C-4 position of podophyllotoxin skeleton on the insecticidal activity was not very obvious. For 4α-(arylacyl)oxy derivatives of 2α-chloro-2'-chloro/bromopicropodophyllotoxin, an electronic effect of the substituents on their phenyl ring at the C-4 position of podophyllotoxin skeleton on the insecticidal activity was observed.
Laboratory of Pharmaceutical Design and Synthesis, College of Sciences, Northwest A&F University , Yangling 712100, Shaanxi Province People's Republic of China.
Lingling
L
Fan
Yong
Y
Guo
Xiaoyan
X
Zhi
Xiang
X
Yu
Hui
H
Xu
D000818:Animals; D018360:Crystallography, X-Ray; D004952:Esters / Q000737:chemistry / Q000494:pharmacology; D054879:Halogenation; D007306:Insecticides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D009036:Moths / Q000187:drug effects*; D011034:Podophyllotoxin / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013237:Stereoisomerism
D004952:Esters; D007306:Insecticides; D011034:Podophyllotoxin