单刀根活性成分的研究
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摘要
单刀根为豆科仪花属植物仪花(Lysidicie rhodostegia Hance)的根，分布于我国广西、广东、云南、贵州等地，为我国民间传统用药，主要用于治疗跌打损伤，风湿骨痛等症。
庾石山教授课题组采用活性跟踪分离的方法，从单刀根乙醇提取物的乙酸乙酯和正丁醇部位分离得到一些结构新颖、具有较强生物活性的化合物。在此研究的基础上，我们采用多种色谱分离技术，从其正丁醇部位极性大的活性组分中分离得到11个化合物。利用波谱和化学方法对其中的10个化合物进行了结构测定和鉴定，其中新化合物8个。这8个新化合物中有6个为具有新型骨架的间苯三酚类衍生物，它们分别具有罕见的螺环苯并二氢呋喃骨架和苄基取代的苯并呋喃并四氢呋喃骨架，并且化合物4分子结构中的两个呋喃环为反式稠合，这在具有苯并呋喃并四氢呋喃结构片段的天然产物中是首次发现(以前发现的均为顺式稠合)；另两个新化合物为间苯三酚类衍生物和二氢菲类衍生物。两个已知化合物为首次从该属植物中分离得到。
新化合物分别为：仪花素A(lysidicin A，1)、仪花素B(lysidicin B，2)、仪花素C(lysidicin C，3)、仪花素D(lysidicin D，4)、仪花素E(lysidicin E，5)、仪花素F(lysidicin F，6)、仪花素G(lysidicin G，7)((10R)-3-methy1-1-[1，3，5，7-tetrahydroxy-10-(4-hydroxyphenyl)-9，10-di-hydro-2-phenanthrenyl]-1-butanone)和仪花素H(lysidicin H，8)(4，6-dihydroxy-5-(3-methylbuty-ryl)-3-(2-oxopropyl)-3-[2，4，6-trihydroxy-3-(3-methylbutyryl)benzyl]-2，3-dihydrobenzo[6]furan-2-one)。
已知化合物被分别鉴定为：(顺)-白藜芦醇3-O-β-D-吡喃葡萄糖苷((Z)-resveratrol 3-O-β-D-glucopyranoside，9)和甲基-α-D-吡喃葡萄糖苷(methyl-α-D-glucopyranoside，10)。
同时，本论文对8个新化合物的生物合成途径进行了初步的推测和探讨，发现它们可能具有独特的生源途径，为开展复杂结构间苯三酚衍生物的仿生合成奠定了基础。
此外，对新化合物3和7进行了抗氧化活性的筛选，抗氧化试验结果表明化合物3和7在10~(-4)，10~(-5)和10~(-6)M时其活性均强于阳性对照物维生素E。
The roots of Lysidice rhodostegia Hance, which is a shrubbery and widely distributed in Guangxi, Guangdong, Yunnan and Guizhou provinces of China, have been used for the treatment of ache, fractures and hemorrhage by local folks in China.
Bioassay-directed separation of the EtOAc and n-BuOH fractions by the group of Prof. Yu led to the isolation and structural elucidation of thirty-two compounds, among which 9 were new compounds, some of them exhibited strong vasodilator and/or anti-oxidant activities. Further investigation on the n-BuOH fraction resulted in the isolation of 11 compounds by using various chromatographic methods, and the structures of 10 of them were elucidated by chemical and spectra methods. Among them, there were six novel compoucds, which possessed unusual spirocyclic benzodihydrofuran and benzofurotetrahydrofuran skeleton. Especially, compound 4 possessed two trans-fused furan rings, which was first discovered among natural products with benzofurofuran fragments. The other two new compounds were phloroglucinol derivative and dihydrophenanthrene derivative, respectively. Both of the two known compounds were isolated from this genus for the first time.
The new compounds were elucidated as lysidicin A (1), lysidicin B (2), lysidicin C (3), lysidicin D (4), lysidicin E (5), lysidicin F (6), lysidicin G (7) ((10R)-3-methyl-1-[1,3,5,7-tetrahydrox-y-10-(4-hydroxyphenyl)-9,10-dihydro-2-phenanthrenyl]-1-butanone), Lysidicin H (8) (4,6-dihydro-xy-5-(3-methylbutyryl)-3-(2-oxopropyl)-3-[2,4,6-trihydroxy-3-(3-methylbutyryl)benzyl]-2,3-dihyd-robenzo[b]furan-2-one).
Besides, the known ones: (Z)-resveratrol 3-O-β-D-glucopyranoside (9) and methyl-α-D-glucop-yranoside (10).
Meanwhile, the particular biogenetic pathways of the new compounds were postulated, which would provide some advice for biomimetic synthesis of phloroglucinol derivatives with complicated structure.
Furthermore, anti-oxidant activities of compounds 3 and 7 were also investigated and they showed stronger anti-oxidant activities than the positive control agent Vitamin E at the concentrations of 10~(-4), 10~(-5) and 10~(-6)M.
庾石山教授课题组采用活性跟踪分离的方法，从单刀根乙醇提取物的乙酸乙酯和正丁醇部位分离得到一些结构新颖、具有较强生物活性的化合物。在此研究的基础上，我们采用多种色谱分离技术，从其正丁醇部位极性大的活性组分中分离得到11个化合物。利用波谱和化学方法对其中的10个化合物进行了结构测定和鉴定，其中新化合物8个。这8个新化合物中有6个为具有新型骨架的间苯三酚类衍生物，它们分别具有罕见的螺环苯并二氢呋喃骨架和苄基取代的苯并呋喃并四氢呋喃骨架，并且化合物4分子结构中的两个呋喃环为反式稠合，这在具有苯并呋喃并四氢呋喃结构片段的天然产物中是首次发现(以前发现的均为顺式稠合)；另两个新化合物为间苯三酚类衍生物和二氢菲类衍生物。两个已知化合物为首次从该属植物中分离得到。
新化合物分别为：仪花素A(lysidicin A，1)、仪花素B(lysidicin B，2)、仪花素C(lysidicin C，3)、仪花素D(lysidicin D，4)、仪花素E(lysidicin E，5)、仪花素F(lysidicin F，6)、仪花素G(lysidicin G，7)((10R)-3-methy1-1-[1，3，5，7-tetrahydroxy-10-(4-hydroxyphenyl)-9，10-di-hydro-2-phenanthrenyl]-1-butanone)和仪花素H(lysidicin H，8)(4，6-dihydroxy-5-(3-methylbuty-ryl)-3-(2-oxopropyl)-3-[2，4，6-trihydroxy-3-(3-methylbutyryl)benzyl]-2，3-dihydrobenzo[6]furan-2-one)。
已知化合物被分别鉴定为：(顺)-白藜芦醇3-O-β-D-吡喃葡萄糖苷((Z)-resveratrol 3-O-β-D-glucopyranoside，9)和甲基-α-D-吡喃葡萄糖苷(methyl-α-D-glucopyranoside，10)。
同时，本论文对8个新化合物的生物合成途径进行了初步的推测和探讨，发现它们可能具有独特的生源途径，为开展复杂结构间苯三酚衍生物的仿生合成奠定了基础。
此外，对新化合物3和7进行了抗氧化活性的筛选，抗氧化试验结果表明化合物3和7在10~(-4)，10~(-5)和10~(-6)M时其活性均强于阳性对照物维生素E。
The roots of Lysidice rhodostegia Hance, which is a shrubbery and widely distributed in Guangxi, Guangdong, Yunnan and Guizhou provinces of China, have been used for the treatment of ache, fractures and hemorrhage by local folks in China.
Bioassay-directed separation of the EtOAc and n-BuOH fractions by the group of Prof. Yu led to the isolation and structural elucidation of thirty-two compounds, among which 9 were new compounds, some of them exhibited strong vasodilator and/or anti-oxidant activities. Further investigation on the n-BuOH fraction resulted in the isolation of 11 compounds by using various chromatographic methods, and the structures of 10 of them were elucidated by chemical and spectra methods. Among them, there were six novel compoucds, which possessed unusual spirocyclic benzodihydrofuran and benzofurotetrahydrofuran skeleton. Especially, compound 4 possessed two trans-fused furan rings, which was first discovered among natural products with benzofurofuran fragments. The other two new compounds were phloroglucinol derivative and dihydrophenanthrene derivative, respectively. Both of the two known compounds were isolated from this genus for the first time.
The new compounds were elucidated as lysidicin A (1), lysidicin B (2), lysidicin C (3), lysidicin D (4), lysidicin E (5), lysidicin F (6), lysidicin G (7) ((10R)-3-methyl-1-[1,3,5,7-tetrahydrox-y-10-(4-hydroxyphenyl)-9,10-dihydro-2-phenanthrenyl]-1-butanone), Lysidicin H (8) (4,6-dihydro-xy-5-(3-methylbutyryl)-3-(2-oxopropyl)-3-[2,4,6-trihydroxy-3-(3-methylbutyryl)benzyl]-2,3-dihyd-robenzo[b]furan-2-one).
Besides, the known ones: (Z)-resveratrol 3-O-β-D-glucopyranoside (9) and methyl-α-D-glucop-yranoside (10).
Meanwhile, the particular biogenetic pathways of the new compounds were postulated, which would provide some advice for biomimetic synthesis of phloroglucinol derivatives with complicated structure.
Furthermore, anti-oxidant activities of compounds 3 and 7 were also investigated and they showed stronger anti-oxidant activities than the positive control agent Vitamin E at the concentrations of 10~(-4), 10~(-5) and 10~(-6)M.
引文
1．江苏新医学院．中药大辞典．上海科学技术出版社，上海，1977，1466．
2. Gao song, Feng Nan, Yu Shishan, Yu Dequan, Wangxiaoliang. Planta Med. 2004, 70, 1128-1134.
3. Gao song, Fu Guangmiao, Fan Lihua, Yu Shishan, Yu Dequan. J. Integ. Plant. Biol. 2005, 47(6), 759-763.
4. Gao song, Yu Shishan, Yu Dequan. Chin. Chem. Lett. 2004, 15(3), 313-315.
5．郜嵩，浮光苗，范丽华，庾石山，于德泉．中国天然药物，2005，3(3)，144-147．
6. Gao song, et al. Phytochemistry. (Contributed)
7．郜嵩．中国医学科学院药物研究所博士论文．2004．
8. Leslie Crombie, Raymond C. F. Jones, Christophe J. Palmer. J. Chem. Soc. Perkin Trans. 1, 1987, 317-312.
9. Zhang Peicheng, Xu Suixu. Phytochemistry. 2001, 57, 1249.
10. William W. Johnson, Thomas M. Harris, F. Peter Guengerich. J. Am. Chem. Soc. 1996, 118, 8213-8217.
11. Leng Chee Chang, Clarissa Gerhauser, Lynda Song, Norman R. Farnsworth, John M. Pezzuto, A. Douglas Kinghorn. J. Nat. Prod. 1997, 60, 869-873.
12. Steven W. Baertschi, Kevin D. Raney, Michael P. Stone, Thomas M. Harris. J. Am. Chem. Soc. 1988, 110, 7929-7931.
13. Takashi Ishida, Stephen V. J. Bouds, John Caldwell, Alex Drake, Mitsuhiro Takeshita. Tetrahedron: Asymmetry. 1996, 7(11), 3113-3118.
14. Peter B. Hulbert, William Klyne, P. Molly Scopes. J. Chem. Research(s), 1981, 27.
15. Karin W. M. Zuurbier, Suen Yingfung, Johannes J. C. Scheffer, Robert Verpoorte. Phytochemisty. 1998, 49(8), 2315-2322.
16. Zegota, H.; Sonntag, C. V.; Z. Naturforsch. B: Anorg. Chem. Org. Chem. 1981, 36, 1331.
17. Jan H. van der Westhuizen, Daneel Ferreira, David G. Roux. J. Chem. Soc. Perkin Trans. 1. 1977, 1517-1521.
18. Riaan Bekker, Rachel S. Smit, E. Vincent Brandt, Daneel Ferreira. Phytochemistry. 1996, 43(3), 673-679.
19．姚新生，等．天然药物化学．第三版．北京：人民卫生出版社，2001，p168．
20. Kurt B. G. Torssell. Natural Product Chemistry: A Mechanistic, Biosynthetic and Ecological Approach, p. 224, Swedish Pharmaceutical Press, Sweded (1997).
21．姚新生，等．天然药物化学．第三版．北京：人民卫生出版社，2001，p167．
2. Gao song, Feng Nan, Yu Shishan, Yu Dequan, Wangxiaoliang. Planta Med. 2004, 70, 1128-1134.
3. Gao song, Fu Guangmiao, Fan Lihua, Yu Shishan, Yu Dequan. J. Integ. Plant. Biol. 2005, 47(6), 759-763.
4. Gao song, Yu Shishan, Yu Dequan. Chin. Chem. Lett. 2004, 15(3), 313-315.
5．郜嵩，浮光苗，范丽华，庾石山，于德泉．中国天然药物，2005，3(3)，144-147．
6. Gao song, et al. Phytochemistry. (Contributed)
7．郜嵩．中国医学科学院药物研究所博士论文．2004．
8. Leslie Crombie, Raymond C. F. Jones, Christophe J. Palmer. J. Chem. Soc. Perkin Trans. 1, 1987, 317-312.
9. Zhang Peicheng, Xu Suixu. Phytochemistry. 2001, 57, 1249.
10. William W. Johnson, Thomas M. Harris, F. Peter Guengerich. J. Am. Chem. Soc. 1996, 118, 8213-8217.
11. Leng Chee Chang, Clarissa Gerhauser, Lynda Song, Norman R. Farnsworth, John M. Pezzuto, A. Douglas Kinghorn. J. Nat. Prod. 1997, 60, 869-873.
12. Steven W. Baertschi, Kevin D. Raney, Michael P. Stone, Thomas M. Harris. J. Am. Chem. Soc. 1988, 110, 7929-7931.
13. Takashi Ishida, Stephen V. J. Bouds, John Caldwell, Alex Drake, Mitsuhiro Takeshita. Tetrahedron: Asymmetry. 1996, 7(11), 3113-3118.
14. Peter B. Hulbert, William Klyne, P. Molly Scopes. J. Chem. Research(s), 1981, 27.
15. Karin W. M. Zuurbier, Suen Yingfung, Johannes J. C. Scheffer, Robert Verpoorte. Phytochemisty. 1998, 49(8), 2315-2322.
16. Zegota, H.; Sonntag, C. V.; Z. Naturforsch. B: Anorg. Chem. Org. Chem. 1981, 36, 1331.
17. Jan H. van der Westhuizen, Daneel Ferreira, David G. Roux. J. Chem. Soc. Perkin Trans. 1. 1977, 1517-1521.
18. Riaan Bekker, Rachel S. Smit, E. Vincent Brandt, Daneel Ferreira. Phytochemistry. 1996, 43(3), 673-679.
19．姚新生，等．天然药物化学．第三版．北京：人民卫生出版社，2001，p168．
20. Kurt B. G. Torssell. Natural Product Chemistry: A Mechanistic, Biosynthetic and Ecological Approach, p. 224, Swedish Pharmaceutical Press, Sweded (1997).
21．姚新生，等．天然药物化学．第三版．北京：人民卫生出版社，2001，p167．