USDA-ARS, Natural Products Utilization Research Unit, University, MS 38677, USA.
Chem Biodivers. 2010 Jul;7(7):1681-97. doi: 10.1002/cbdv.201000031.
An Aedes aegypti larval toxicity bioassay was performed on compounds representing many classes of natural compounds including polyacetylenes, phytosterols, flavonoids, sesquiterpenoids, and triterpenoids. Among these compounds, two eudesmanolides, alantolactone, and isoalantolactone showed larvicidal activities against Ae. aegypti and, therefore, were chosen for further structure-activity relationship study. In this study, structural modifications were performed on both alantolactone and isoalantolactone in an effort to understand the functional groups necessary for maintaining and/or increasing its activity, and to possibly lead to more effective insect-control agents. All parent compounds and synthetic modification reaction products were evaluated for their toxic activities against Ae. aegypti larvae and adults. Structure modifications included epoxidations, reductions, catalytic hydrogenations, and Michael additions to the alpha,beta-unsaturated lactones. None of the synthetic isomers synthesized and screened against Ae. aegypti larvae were more active than isoalantolactone itself which had an LC(50) value of 10.0 microg/ml. This was not the case for analogs of alantolactone for which many of the analogs had larvicidal activities ranging from 12.4 to 69.9 microg/ml. In general, activity trends observed from Ae. aegypti larval screening were not consistent with observations from adulticidal screening. The propylamine Michael addition analog of alantolactone was the most active adulticide synthesized with an LC(50) value of 1.07 microg/mosquito. In addition, the crystal structures of both alantolactone and isoalantolactone were determined using CuK(alpha) radiation, which allowed their absolute configurations to be determined based on resonant scattering of the light atoms.
采用代表多种天然化合物类别的化合物对埃及伊蚊幼虫进行了毒性生物测定，包括多炔、植物甾醇、类黄酮、倍半萜和三萜。在这些化合物中，两种艾里莫烷型倍半萜内酯——土木香内酯和异土木香内酯对埃及伊蚊具有杀幼虫活性，因此被选择用于进一步的构效关系研究。在这项研究中，对土木香内酯和异土木香内酯进行了结构修饰，以了解维持和/或增加其活性所需的功能基团，并可能导致更有效的昆虫控制剂。所有母体化合物和合成修饰反应产物均针对其对埃及伊蚊幼虫和成虫的毒性活性进行了评估。结构修饰包括α，β-不饱和内酯的环氧化、还原、催化氢化和迈克尔加成。与异土木香内酯本身相比，针对埃及伊蚊幼虫合成和筛选的合成异构体均没有更高的活性，异土木香内酯本身的 LC(50)值为 10.0μg/ml。而土木香内酯的类似物则并非如此，其中许多类似物的杀幼虫活性范围为 12.4 至 69.9μg/ml。一般来说，从埃及伊蚊幼虫筛选中观察到的活性趋势与成虫杀活性筛选的观察结果不一致。土木香内酯的丙胺迈克尔加成类似物是合成的最活性的杀成虫剂，LC(50)值为 1.07μg/只。此外，还使用 CuK(alpha)射线确定了土木香内酯和异土木香内酯的晶体结构，这使得可以根据轻原子的共振散射来确定它们的绝对构型。
