Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis  

作　　者：Jun-Su Zhou Long Cheng Yuan Gao Zhan-Peng Ge Bin Zhou Jing-Ya Li Jin-Xin Zhao Jian-Min Yue 

机构地区：[1]State Key Laboratory of Drug Research,Shanghai Institute of Materia Medica,Chinese Academy of Sciences,Shanghai 201203,China [2]Shandong Laboratory of Yantai Drug Discovery,Bohai Rim Advanced Research Institute for Drug Discovery,Yantai 264117,China

出　　处：《Engineering》2024年第7期144-154,共11页工程（英文）

基　　金：support from the National Natural Science Foundation of China(22237007 and 22177122);the Biological Resources Program of Chinese Academy of Sciences(CAS)(KFJ-BRP-008-001);the Youth Innovation Promotion Association of Chinese Academy of Sciences(2022282)is gratefully acknowledged.We thank Prof.Shi-Man Huang,Department of Biology,Hainan University,China,for the identification of the plant material.

摘　　要：Four new norditerpenoid heterodimers with different dimerization patterns-namely,trigofragiloids A-C(denoted as compounds 1-3)and(+)-and(-)-trigofragiloid D(compound 4)-and three new phenanthrenone norditerpenoids-namely,trigofragiloids E-G(compounds 5-7)-were isolated from Trigonostemon fragilis.Compounds 1 and 2 feature a novel heterodimeric carbon skeleton formed by the conjugation of a tetra-norditerpenoid and an ennea-norditerpenoid;they have been identified as class 2 atropisomers by means of quantum chemical calculations.Compound 3 is an unprecedented phenylpropanoid-norditerpenoid adduct with a new dimerization pattern.Compounds(+)-and(-)-4 are the first example of S-shaped 1,4-dioxane-fused norditerpenoid dimers.Inspired by the structure elucidation of compound 4,two co-occurring analogues,actephilol A and epiactephilol A,were structurally revised as a pair of geometrical isomers and were identified as two pairs of enantiomers,(+)-and(-)-8 and(+)-and(-)-9,respectively.Their structures were characterized using a combined method.Notably,compound 7 exhibits remarkable adenosine triphosphate-citrate lyase(ACLY)inhibition with a halfmaximal inhibition concentration(IC50)value of(0.46±0.11)lmol·L^(-1),as active as the positive control BMS-303141,and a molecular docking study offers deep insight into the interaction between compound 7 and ACLY.

关 键 词：Norditerpenoid heterodimer Trigonostemon fragilis EUPHORBIACEAE Trigofragiloid Structural revision Adenosine triphosphate-citrate lyase(ACLY) inhibitory activity 

分 类 号：TQ460.1[化学工程—制药化工]