Laeviganoids A–T, ent-Clerodane-Type Diterpenoids from Croton laevigatus

Laeviganoids A–T (1–20), 20 new ent-clerodane-type diterpenoids featuring a 2-furanone (1–3) or a furan (4–20) ring, as well as six analogues (21–26), were isolated from the roots of Croton laevigatus. Their structures were determined by spectroscopic data analysis, experimental electronic circular dichroism measurements, and X-ray crystallographic studies. Compounds 4–6, 16, 21–24, and 26 could influence the anti-inflammatory protumoral phenotype of macrophages. Among these compounds, 21 and 26 are the most potent, as evidenced by consistently downregulating the classic anti-inflammatory cytokine IL-10 and upregulating the classic pro-inflammatory cytokine TNF-α on the secretion level in RAW 264.7 cells.

本研究从光叶巴豆（Croton laevigatus）的根部中分离得到20个全新的莱维甘诺类（Laeviganoids）化合物A~T（1~20），该类化合物属于对映-克罗烷型二萜（ent-clerodane-type diterpenoids），分别带有2-呋喃酮（2-furanone，1~3）或呋喃（furan，4~20）环结构；此外还分离得到6个类似物（21~26）。其结构通过光谱数据分析、实验电子圆二色谱（electronic circular dichroism，ECD）测试以及X射线晶体衍射研究得以确证。化合物4~6、16、21~24及26可调控巨噬细胞的抗炎型促肿瘤表型。其中，21和26的活性最为显著：在RAW 264.7细胞的分泌水平上，它们可持续下调经典抗炎细胞因子白细胞介素10（Interleukin-10，IL-10）的分泌，并上调经典促炎细胞因子肿瘤坏死因子α（Tumor Necrosis Factor-α，TNF-α）的分泌。