Synthesis and Quantitative Structure鈥揂ctivity Relationship (QSAR) Study of Novel Isoxazoline and Oxime Derivatives of Podophyllotoxin as Insecticidal Agents

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• 作者：Yi Wang ; Yonghua Shao ; Yangyang Wang ; Lingling Fan ; Xiang Yu ; Xiaoyan Zhi ; Chun Yang ; Huan Qu ; Xiaojun Yao ; Hui Xu
• 刊名：Journal of Agricultural and Food Chemistry
• 出版年：2012
• 出版时间：August 29, 2012
• 年：2012
• 卷：60
• 期：34
• 页码：8435-8443
• 全文大小：430K
• 年卷期：v.60,no.34(August 29, 2012)
• ISSN：1520-5118

文摘

In continuation of our program aimed at the discovery and development of natural-product-based insecticidal agents, 33 isoxazoline and oxime derivatives of podophyllotoxin modified in the C and D rings were synthesized and their structures were characterized by Proton nuclear magnetic resonance (¹H NMR), high-resolution mass spectrometry (HRMS), electrospray ionization鈥搈ass spectrometry (ESI鈥揗S), optical rotation, melting point (mp), and infrared (IR) spectroscopy. The stereochemical configurations of compounds 5e, 5f, and 9f were unambiguously determined by X-ray crystallography. Their insecticidal activity was evaluated against the pre-third-instar larvae of northern armyworm, Mythimna separata (Walker), in vivo. Compounds 5e, 9c, 11g, and 11h especially exhibited more promising insecticidal activity than toosendanin, a commercial botanical insecticide extracted from Melia azedarach. A genetic algorithm combined with multiple linear regression (GA鈥揗LR) calculation is performed by the MOBY DIGS package. Five selected descriptors are as follows: one two-dimensional (2D) autocorrelation descriptor (GATS4e), one edge adjacency indice (EEig06x), one RDF descriptor (RDF080v), one three-dimensional (3D) MoRSE descriptor (Mor09v), and one atom-centered fragment (H-052) descriptor. Quantitative structure鈥揳ctivity relationship studies demonstrated that the insecticidal activity of these compounds was mainly influenced by many factors, such as electronic distribution, steric factors, etc. For this model, the standard deviation error in prediction (SDEP) is 0.0592, the correlation coefficient (R²) is 0.861, and the leave-one-out cross-validation correlation coefficient (Q²_loo) is 0.797.

Keywords:

Podophyllotoxin; insecticidal activity; botanical insecticide; structural modification; QSAR; Mythimna separata Walker