Fifteen new polycyclic polyprenylated acylphloroglucinols (PPAPs), hyperforatones A–O (1–15), along with 3 structurally related analogues (16–18), were isolated from the stems and leaves of Hypericum perforatum. Their structures and absolute configurations were established by a combination of NMR spectroscopic analyses, experimental and calculated electronic circular dichroism (ECD), modified Mosher's methods, Rh₂(OCOCF₃)₄- and [Mo₂(OAc)₄]-induced ECD, X-ray crystallography, and the assistance of quantum chemical predictions (QCP) of ¹³C NMR chemical shifts. Compound 5 was found to be the first PPAP decorated by a rare 2,2,4,4,5-(pentamethyltetrahydrofuran-3-yl)methanol moiety and an oxepane ring. Furthermore, the isolates were screened for their acetylcholinesterase (AChE) and β-site amyloid precursor protein cleaving enzyme 1 (BACE1) inhibitory activities. Compounds 5, 10, 11, and 15 showed desirable AChE inhibitory activities (IC₅₀ 6.9–9.2 μM) and simultaneously inhibited BACE1 (at a concentration of 5 μM) with inhibition rates of 50.3%, 34.3%, 47.2%, and 34.6%, respectively. Interestingly, compound 5 showed the most balanced inhibitory activities against both AChE and BACE1 of all the tested compounds, which means that 5 could serve as the first valuable dual-targeted PPAP for the treatment of Alzheimer's disease. Preliminary molecular docking studies of 5 with BACE1 and AChE were also performed.

中文翻译：

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贯叶连翘的生物活性多环多戊烯基化酰基葡糖醇

从贯叶连翘的茎和叶中分离出了十五种新的多环多烯丙基化酰基间苯三酚（PPAPs），hyperforatones A–O（1–15）以及3种与结构相关的类似物（16–18）。它们的结构和绝对构型是通过NMR光谱分析，实验和计算的电子圆二色性（ECD），改良的Mosher方法，Rh ₂（OCOCF ₃）_4-和[Mo ₂（OAc）₄ ]诱导的ECD， X射线晶体学，以及¹³ C NMR化学位移的量子化学预测（QCP）的辅助。化合物5被发现是第一个由稀有的2,2,4,4,5-（五甲基四氢呋喃-3-基）甲醇部分和氧杂环丁烷环修饰的PPAP。此外，筛选了分离物的乙酰胆碱酯酶（AChE）和β位淀粉样蛋白前体蛋白裂解酶1（BACE1）抑制活性。化合物5，10，11，和15个显示出希望的乙酰胆碱酯酶抑制活性（IC ₅₀ 6.9-9.2μM）和抑制同时BACE1（5μM的浓度），用50.3％，34.3％，47.2％，和34.6％的抑制率， 分别。有趣的是，化合物5在所有测试化合物中均显示出对AChE和BACE1的最平衡的抑制活性，这意味着5可以作为治疗阿尔茨海默氏病的第一个有价值的双重靶向PPAP。还进行了5与BACE1和AChE的分子对接的初步研究。