Laboratory of Pharmaceutical Design & Synthesis, College of Sciences, Northwest A&F University, Yangling 712100, Shaanxi Province, People's Republic of China.
J Agric Food Chem. 2013 Aug 28;61(34):8148-55. doi: 10.1021/jf4025079. Epub 2013 Aug 15.
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.
在我们继续进行旨在发现和开发天然产物杀虫剂的项目中，我们已经制备了三系列新型的 4α-(acyloxy)-2'（2'，6'）-（二）卤代鬼臼毒素衍生物，对鬼臼毒素的 C 和 E 环进行了修饰，鬼臼毒素是一种天然存在的芳基四氢呋喃木脂素，从尼泊尔鬼臼 Podophyllum hexandrum 的根和根茎中分离出来。它们的结构通过（1）H NMR、HRMS、ESI-MS、旋光度和熔点得到了很好的表征。化合物 5s、6b、6d 和 7q 的立体化学构型通过单晶 X 射线衍射得到了明确的确认。它们的杀虫活性在浓度为 1mg/mL 时，通过体内试验针对东方粘虫 Mythimna separata Walker 的预 3 龄幼虫进行了评估。这些衍生物可能表现出抗蜕皮激素的作用。在所有衍生物中，特别是化合物 5a、5n、7f、7n 和 7w 表现出最强的杀虫活性，最终死亡率约为 70%。这表明，在鬼臼毒素的 E 环的 C2' 或 C2' 和 C6' 位置上引入氯或溴原子对于获得有效化合物是必要的。这将为进一步设计、结构修饰和开发鬼臼毒素衍生物作为杀虫剂铺平道路。
