Highly Aromatic Norditerpenoid Heterodimers and Monomers from Trigonostemon fragilis

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) mu mol center dot 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. (c) 2023 THE AUTHORS. Published by Elsevier LTD on behalf of Chinese Academy of Engineering and Higher Education Press Limited Company.