摘要
云南狗牙花(Ervatamia yunnanensis Tsiang)是夹竹桃科狗牙花属植物,分布于云
南、广西。民间主要用于治疗高血压、腹痛等。云南狗牙花总碱具有非常强的镇痛及
脑保护作用。为了进一步寻找具有活性的化学成分,我们对云南狗牙花生物碱及其它
部分进行了成分分离,应用现代层析方法共分得16个化合物,根据理化数据和光谱
分析(~1H-NMR,~(13)C-NMR,DEPT,~1H-~1H COSY,~(13)C-~1H COSY,NOESY,COLOC,HMQC,
HMBC,EI-MS,FAB-MS)确定了它们的化学结构。并对总碱及部分单体化合物进行了
抗成瘾和抗肿瘤活性实验。发现云南狗牙花总碱能够阻断Morphine依赖小鼠复吸模
型的再点燃。并且本身不具有阿片样身体依赖性,但各单体化合物的活性还有待进一
步观察。16个化合物的结构如下:
SUB 1 β-谷甾醇(β-sitosterol)
SUB 2 胡萝卜甙(dancosterol)
SUB 3 丁香树脂醇(syringaresinol)
SUB 4 pinoresinol
SUB 5 羽扇豆醇乙酸酯(lupenyl acetate)
SUB 6 苦参碱(matrine)
SUB 7 冠狗牙花碱(coronaridine)
SUB 8 19,20-dihydroisostitsirikine
SUB 9 19-s-heyneanine
SUB 10 ibogamine
SUB 11 EYA-1
SUB 12 19-s-voacangarine and 11-methoxyl-19s-heyneanine
SUB 13 EYA-2
SUB 14 conodurine
SUB 15 19,20-E-vallesamine
SUB 16 10-hydroxy-19,20-dihydroisositsirikine
以上化合物中,SUB2、SUB5、SUB8、SUB9、SUB12、SUB13、SUB14、SUB15
均为首次从该植物中分得,其中SUB3、SUB4、SUB6为该属植物中首次发现的结构
类型,SUB11、SUB16为新化合物。
Dried stem of Ervatamia yunnanensis Tsiang is a folk medicine used for the treatment of hypertension and abdominal pain. The plant is a shrub or arbor distributed in the Yunnan and Guangxi provinces. Total Ervatamia yunnanensis Tsiang alkaloid showed significant antinociceptive effects and cerebral protecttive effects. In order to find the active constituents, fifteen compounds and a mixture with two alkaloids have been isolated from the total Ervatamia yunnanensis Tsiang alkaloid and the other part. The structure of the compounds were elucitated by the analysis of EI-MS, 1H-NMR, 13CNMR and 2D-NMR. In the pharmacological experiments, the total Ervatamia yunnanensis Tsiang alkaloid showed the effects on block of rein~tatement of place preference in relapse model morphine dependment mice. And it didn’t show the psychic dependence and physical dependence itself in mice. The compounds are showed as the following:
SUB 1 f3-sitosterol
SUB 2 dancosterol
SUB 3 syringaresinol
SUB 4 pinoresinol
SUB 5 lupenyl acetate
SUB 6 matrine
SUB 7 coronaridine
SUB 8 19, 20-dihydroisostitsirikine
SUB 9 1 9-s-heyneanine
SUB 10 ibogamine
SUB 11 EYA-l
SUB 12 1 9-s~voacangarine and 11 -methoxyl- 1 9s-heyneanine
SUB 13 EYA-2
SUB 14 conodurine
SUB 15 19, 20-E-vallesamine
SUB 16 10-hydroxy-19, 20-dihydroisositsirikine
SUB2~ SUBS. SUB8~ SUB9~. SUB12-. SUB13.. SUB14 and SUB 15 were isolated from Ervatamia yunnanensis for the first time. SUB3 .. SUB4 -. SUB6 were first isolated from Ervatamia genus. SUB 11 and SUB 16 are new compounds.
引文
1. 中国科学院中国植物志编辑委员会:中国植物志,科学出版社,北京,1977,63: 98-114
2. 西双版纳民族医药调研办公室:西双版纳傣族药志,西双版纳卫生局、西双版纳 科学技术委员会出版,第 3 册,1981,133
3. 喻阳,刘吉开.云南植物研究,1999,21(2) :260-264
4. Liu Gui,Liu,Xin,and Feng Xiao-Zhang.Planta Medica,1988,54(6) :519-521
5. 喻阳,高锦明,刘吉开.云南植物研究,1999,21(3) :399-450
6. 郭学敏等.药学学报,1995,30(12) :931
7. 叶苹,茅一青,沈锡定.贵阳医学院学报,1994,19(4) :327-329
8. Barbara Uermes,Orro Seligmann and Hildebert Wagner.Phytochemistry,1991,30(9) : 3087-3089
9. 刘桂芳,杨松松,杨志强等.中药通报,1987,12(8) :36-38
10. Cahill Ret al.Org.Magn Reson,1972;4:283
11. 运文慧,陈玉斌,冯孝章.中草药,1994,25(3) :118-120
12. Fascale Clivio,Bernard Richard,Jean-Robert Deverre et al.Phytochemistry,1991, 30(11) :3785-3792
13. Sarath P.Gunasekera,Geoffrey A.Cordell and Norman R.Farnsnorth.Phytochemistry, 1980,19(19) ,1213-1218
14. Damak M et al.Tetrahedron Lett,1976,39:3531
15. Tatsuo Yamauchi,Fumiko Abe,Rong-Fi Chen,et al.Phytochemistry,1990,29(11) : 3547-3552
16. 丛浦珠.质谱学在天然有机化学中的应用,北京:科学出版社,1987,95-109
17. 周韵丽,黄丽瑛,胡玉敏等.中草药,1988,19(12) :6-8
18. Atta-ur-Rahman,Khisal Ahmad Ahi,Syed Ali Abbas et al.Heterocycles,1987,26(2) : 413-419
19. Ernest Wenkert,Ching-Jer Chang,H.P.S.Chawla.Journal of the American Chemical Society,1976,98(12) :3645-3655