金刚纂二萜类成分研究

Diterpenes from stem bark of Euphorbia neriifolia

目的研究有毒药用植物金刚纂Euphorbia neriifolia茎皮的二萜类化学成分及其抗HIV-1活性。方法利用硅胶、ODS、MCI CHP-20P、Sephadex LH-20等柱色谱和高效液相色谱技术进行系统分离,通过理化性质和NMR、MS波谱数据鉴定化合物结构;采用HIV-1病毒株NL4-3感染的人淋巴MT-4细胞作为细胞检测模型对所得化合物进行抗HIV-1活性测试。结果从金刚纂茎皮的丙酮水提取物的醋酸乙酯萃取部分分离得到9个二萜类化合物,分别被鉴定为12α-乙酰氧基-3β,7α-二羟基-8α-甲氧基续随子烷(1)、3β,8α,12α-三乙酰氧基-7α-苯甲酰氧基续随子烷(2)、3β,8α,12α-三乙酰氧基-7α-巴豆酰氧基续随子烷(3)、对映-3-氧代阿替生烷-16α,17-缩丙酮(4)、13β-羟基-3,15-二氧代阿替生烷-16-烯(5)、对映-3β,(13S)-二羟基阿替生烷-16-烯-14-酮(6)、3β,13(S)-二羟基阿替生烷-16-烯-14-酮(7)、对映-(13S),18-二羟基阿替生烷-16-烯-3,14-二酮(8)、4,13β-二羟基-14-氧代-3,4-开环阿替生烷-16-烯-3-酸甲酯(9)。结论化合物1为新天然产物,化合物2~4、6~8为首次从该植物中分离得到,药理实验结果表明化合物4具有一定的抗HIV-1活性,EC50为8.7μg/m L(SI=1.92)。

Objective To investigate the diterpenes from the stem bark of Euphorbia neriifolia L. and their anti-HIV-1 activity. Methods The chemical constituents were isolated and purified by column chromatography over silica gel, ODS, MCI CHP-20 P, Sephadex LH-20, and preparative HPLC. Their structures were identified by the analysis of their physicochemical properties and the spectral data of NMR and MS. The anti-HIV-1 activity of the compounds was tested by cell detection models established by HIV-1 NL4-3 infected MT-4 cells. Results Nine compounds were isolated from the stem bark of the plant, namely 12α-acetoxy-3β,7α-dihydroxy-8α-methoxyingol（1）, 3β,8α,12α-triacetoxy-7α-benzoyloxyingol（2）, 3β,8α,12α-triacetoxy-7α-tigloyloxyingol（3）, ent-3-oxoatis-16α,17-acetonide（4）, 13β-hydroxy-3,15-dioxoatis-16-ene（5）, ent-3β,（13S）-dihydroxyatis-16-en-14-one（6）, atis-16-en-14-oxo-3β,13（S）-diol（7）, ent-（13S）,18-dihydroxyatis-16-ene-3,14-dione（8）, 4,13β-dihydroxy-14-oxo-3,4-secoatis-16-en-3-oic acid methyl ester（9）. Conclusion Compound 1 is a new natural product. Compounds 2—4, and 6—8 are isolated from the plant for the first time. Furthermore, compound 4 exhibited moderate anti-HIV-1 activities, with EC50 values of 8.7 μg/m L（SI = 1.92）.