山胡椒根中1个新的倍半萜类成分

A new sesquiterpenoid from roots of Lindera glauca

目的 挖掘山胡椒Lindera glauca根的倍半萜类成分,以期寻找到具有潜在抗炎活性的先导化合物。方法 运用正相硅胶、反相硅胶、Sephadex LH-20凝胶及制备型高效液相色谱等对山胡椒石油醚部位化学成分进行分离纯化,并综合采用HRESIMS、NMR、IR、UV、OR、ECD量子化学计算等技术确定化合物的平面和绝对构型;运用脂多糖(lipopolysaccharide,LPS)诱导的RAW264.7细胞体外炎症模型对所制备化合物的抗炎活性进行初步评价。结果 从山胡椒石油醚部位分离得到10个倍半萜化合物,分别鉴定为(4R,7R,10S)-4-羟基-4,10-二甲基-5-羰基-1(6),11(13)-二烯-12-羧酸-萘酮(1)、linderaguaianol C(2)、(-)-(4S,7S,10S)-2-oxo-guaia-1(5),11(13)-dien-12-oic acid(3)、一支蒿酮酸(4)、针叶春黄菊酸(5)、xylaguaianol D(6)、β-木香酸(7)、3α-hydroxycostic acid(8)、ilicic acid(9)、异一枝蒿酮酸(10)。结论 化合物1为新化合物,命名为一支蒿酮酸M(rupestonic acid M);化合物2为首次从天然产物中分离得到并确定了其绝对构型,化合物1~4、6~9为首次从山胡椒中分离得到。化合物5~7、9显示出较强的抗炎活性,具有抗炎药物研发和活性分子结构修饰的潜在价值。

Objective To find the sesquiterpenoids with potent anti-inflammatory activities from the roots of Shanhujiao(Lindera glauca). Methods The constituents were obtained by comprehensive use of silica gel, ODS, sephadex LH-20 and semi-preparative HPLC. Their structures, including their absolute configurations were elucidated by extensive spectroscopic analysis such as HRESIMS,NMR, IR, UV, OR and ECD quantum chemical calculations. All the isolates were tested for the anti-inflammatory activities using the lipopolysaccharide(LPS)-activated RAW264.7 cells. Results Ten sesquiterpene compounds were isolated from petroleum ether extract of the roots of L. glauca and identified as(4R,7R,10S)-4-hydroxy-4,10-dimethyl-5-oxo-1(6),11(13)-dien-12-oic acid-naphthyl ketone(1), linderaguaianol C(2),(-)-(4S,7S,10S)-2-oxo-guaia-1(5),11(13)-dien-12-oic acid(3), rupestonic acid(4), aciphyllic acid(5), xylaguaianol D(6), β-costic acid(7), 3α-hydroxycostic acid(8), ilicic acid(9), and isorupestonic acid(10). Conclusion Compound 1 is a new compound, named rupestonic acid M. Compound 2 is isolated from natural source for the first time and its absolute configuration was confirmed using ECD caculations. Compounds 1—4 and 6—9 are obtained from L. glauca for the first time. Furthermore, compounds 5—7 and 9 showed potent anti-inflammatory effects and have potential value for anti-inflammatory drug development and structural modification of active molecules.