Forrestiacids A (1) and B (2) are a novel class of [4+2] type pentaterpenoids derived from a rearranged lanostane moiety (dienophile) and an abietane unit (diene). These unprecedented molecules were isolated using guidance by molecular ion networking (MoIN) from Pseudotsuga forrestii, an endangered member of the Asian Douglas Fir Family. The intermolecular hetero-Diels–Alder adducts feature an unusual bicyclo[2.2.2]octene ring system. Their structures were elucidated by spectroscopic analysis, GIAO NMR calculations and DP4+ probability analyses, electronic circular dichroism calculations, and X-ray diffraction analysis. This unique addition to the pentaterpene family represents the largest and the most complex molecule successfully assigned using computational approaches to predict accurately chemical shift values. Compounds 1 and 2 exhibited potent inhibitory activities (IC₅₀s <5 μM) of ATP-citrate lyase (ACL), a new drug target for the treatment of glycolipid metabolic disorders including hyperlipidemia. Validating this activity 1 effectively attenuated the de novo lipogenesis in HepG2 cells. These findings provide a new chemical class for developing potential therapeutic agents for ACL-related diseases with strong links to traditional medicines.

中文翻译：

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Forrestiacids A 和 B，ACL 和脂肪生成的五萜类抑制剂：扩展计算 NMR 方法在复杂天然产物结构分配中的局限性

Forrestiacids A ( 1 ) 和 B ( 2 ) 是一类新的 [4+2] 型五萜类化合物，衍生自重排的羊毛甾烷部分（亲二烯体）和松香烷单元（二烯）。这些前所未有的分子是使用来自Pseudotsuga forrestii的分子离子网络 (MoIN) 的指导分离出来的，亚洲花旗松科的濒危成员。分子间杂 Diels-Alder 加合物具有不寻常的双环 [2.2.2] 辛烯环系统。通过光谱分析、GIAO NMR 计算和 DP4+ 概率分析、电子圆二色性计算和 X 射线衍射分析阐明了它们的结构。这种对五萜家族的独特补充代表了使用计算方法成功分配的最大和最复杂的分子，以准确预测化学位移值。化合物 1和2表现出有效的抑制活性 (IC ₅₀ s <5  μM) 的 ATP-柠檬酸裂解酶 (ACL)，一种用于治疗包括高脂血症在内的糖脂代谢紊乱的新药物靶点。验证此活动1有效地减弱了 HepG2 细胞中的从头脂肪生成。这些发现为开发与传统药物密切相关的 ACL 相关疾病的潜在治疗药物提供了新的化学类别。