Laboratory of Plant Biotechnology and Ecosystem Valorization, Faculty of Sciences, Chouaib Doukkali University, Research Unit: Natural Resource Valorizations, P.O. Box 20, 24000, El Jadida, Morocco.
Laboratory of Biomolecular Chemistry, Natural Substances and Reactivity, URAC 16, Faculty of Sciences Semlalia, Cadi Ayyad University, P.O. Box 2390, 40000, Marrakech, Morocco.
Chem Biodivers. 2020 Sep;17(9):e2000287. doi: 10.1002/cbdv.202000287. Epub 2020 Sep 8.
Semisynthetic functionalized triterpenes (4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3β-yl acetate; 4α,14-dimethyl-5α-cholest-8-ene-3,7,11-trione; 4α,14-dimethyl-5α-cholesta-7,9(11)-dien-3-one and 4α,14-dimethyl-5α-cholest-8-en-3β-yl acetate), previously prepared from 31-norlanostenol, a natural insecticide isolated from the latex of Euphorbia officinarum, have been subjected to oxidation with hydrogen peroxide (H O ) and iodosobenzene (PhIO) catalyzed by porphyrin complexes (cytochrome P-450 models) in order to obtain optimized derivatives with high regioselectivity. The main transformations were epoxidation of the double bonds and hydroxylations of non-activated C-H groups and the reaction products were 25-hydroxy-4α,14-dimethyl-5α-cholesta-7,9(11)-dien-3β-yl acetate (59 %), 25-hydroxy-4α,14-dimethyl-5α-cholest-8-ene-3,7,11-trione (60 %), 4α,14-dimethyl-5α,7β-7,8-epoxycholest-9(11)-en-3-one (22 %), 8-hydroxy-4α,14-dimethyl-5α-cholest-9(11)-ene-3,7-dione (16 %), 12α-hydroxy-4α,14-dimethyl-5α,7β-7,8-epoxycholest-9(11)-en-3-one (16 %), and 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3β-yl acetate (26 %), respectively. We also investigated the insect (Myzus persicae, Rhopalosiphum padi and Spodoptera littoralis) antifeedant and postingestive effects of these terpenoid derivatives. None of the compounds tested had significant antifeedant effects, however, all were more effective postingestive toxicants on S. littoralis larvae than the natural compound 31-norlanostenol, with 4α,14-dimethyl-5α,8α-8,9-epoxycholestan-3β-yl acetate being the most active. The study of their structure-activity relationships points out at the importance of C3 and C7 substituents.
半合成功能化三萜（4α,14-二甲基-5α,8α-8,9-环氧胆甾烷-3β-基乙酸酯；4α,14-二甲基-5α-胆甾-8-烯-3,7,11-三酮；4α,14-二甲基-5α-胆甾-7,9(11)-二烯-3-酮和 4α,14-二甲基-5α-胆甾-8-烯-3β-基乙酸酯），先前从天然杀虫剂 31-诺兰醇中制备得到，该杀虫剂从大戟属植物乳胶中分离出来，已经用过氧化氢（H2O2）和碘苯（PhIO）进行了氧化，并用卟啉配合物（细胞色素 P-450 模型）进行了催化，以获得具有高区域选择性的优化衍生物。主要的转化是双键的环氧化和非活性 C-H 基团的羟基化，反应产物为 25-羟基-4α,14-二甲基-5α-胆甾-7,9(11)-二烯-3β-基乙酸酯（59%）、25-羟基-4α,14-二甲基-5α-胆甾-8-烯-3,7,11-三酮（60%）、4α,14-二甲基-5α,7β-7,8-环氧胆甾-9(11)-烯-3-酮（22%）、8-羟基-4α,14-二甲基-5α-胆甾-9(11)-烯-3,7-二酮（16%）、12α-羟基-4α,14-二甲基-5α,7β-7,8-环氧胆甾-9(11)-烯-3-酮（16%）和 4α,14-二甲基-5α,8α-8,9-环氧胆甾烷-3β-基乙酸酯（26%）。我们还研究了这些萜类衍生物对昆虫（桃蚜、麦长管蚜和斜纹夜蛾）的拒食和取食后效应。测试的化合物均没有显著的拒食作用，但对斜纹夜蛾幼虫的取食后毒性均高于天然化合物 31-诺兰醇，其中 4α,14-二甲基-5α,8α-8,9-环氧胆甾烷-3β-基乙酸酯的活性最高。对它们的结构-活性关系的研究指出了 C3 和 C7 取代基的重要性。
