(±)-Hypandrone A (1), a pair of highly modified polycyclic polyprenylated acylphloroglucinol (PPAP) enantiomers, with an unprecedented caged 2,8,17-trioxapentacyclo-[11.4.2.0^1,9.0^4,9.0^10,15]-nonadecane core, were isolated from the fruits of Hypericum androsaemum. The racemate (±)-1 was successfully separated into the two optically pure enantiomers (ee ≥ 99%) using a preparative HPLC system. Their structures including absolute configurations were elucidated via spectroscopic analyses, electronic circular dichroism calculations, and single-crystal X-ray diffraction. Biological studies revealed that (−)-1 is a potent inhibitor of the NLRP3 inflammasome pathway and could inhibit the protein expression of NLRP3, ASC, cleaved caspase-1 and the active form N-GSDMD fragment, thereby blocking NLRP3 inflammasome-induced pyroptosis.

中文翻译：

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(±)-Hypandrone A，一对来自金丝桃的多环聚异戊二烯化酰基间苯三酚对映体，具有笼状 7/6/5/6/6 五环骨架

(±)-Hypandrone A ( 1 ) 是一对高度改性的多环聚异戊二烯酰基间苯三酚 (PPAP) 对映体，具有前所未有的笼状 2,8,17-三氧五环-[11.4.2.0 ^1,9 .0 ^4,9 .0 ^{10 ,15} ]-十九烷核心，从金丝桃的果实中分离出来。使用制备型 HPLC 系统成功地将外消旋体 (±)- 1分离成两种光学纯的对映体 (ee ≥ 99%)。通过光谱分析、电子圆二色性计算和单晶 X 射线衍射阐明了它们的结构，包括绝对构型。生物学研究表明，(−)- 1是NLRP3炎症小体通路的有效抑制剂，可抑制NLRP3、ASC、cleaved caspase-1和活性形式N-GSDMD片段的蛋白表达，从而阻断NLRP3炎症小体诱导的细胞焦亡。