朝鲜淫羊藿和万山淫羊藿化学成分的研究
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摘要
本文通过各种柱层析技术并借助现代波谱学手段，对中国药典(1990)收载的小檗科(Berberidaceae)植物朝鲜淫羊藿(Epimedium koreanum Nakai)和新命名的万山淫羊藿(E．wanshanense)的化学成分进行了研究。
从朝鲜淫羊藿地上部分的乙酸乙酯提取物中分离鉴定了四十四个(1～44)天然产物，其中十一个(2、9、10、11、14、16、18、26、31、36和44)为新化合物，分别命名为：朝藿酮A(2)，朝藿素A(18)、B(9)、C(14)、D(36)，朝藿甙A(10)、B(11)、C(26)、D(16)、E(31)，朝藿菲甙A(44)。
从万山淫羊藿全草的乙酸乙酯和正丁醇提取物中分离得到十六个(45～60)已知成分。
在新化合物结构鉴定过程中，除紫外、红外、质谱和一维核磁共振谱外，还充分运用了一些二维核磁共振技术，如~1H—~1H COSY、~1H—~(13)C COSY、~1H—~1H TOCSY、尤其是~1H—~(13)C long range COSY(HMBC)谱等。正是基于二维核磁共振谱分析，27、38以及29(58)、30、32(59)、33(48)、34、49、50、52、53、54的双糖被确定为1→2连接。本文以上述双糖1→2连接的光谱标准，对文献报道的脱水淫羊藿素和去甲脱水淫羊藿素3—O—L一鼠李糖—(1→2或1→4)—L—鼠李糖甙、3—O—D—木糖—(1→2或1→4)—L—鼠李糖甙及3—O—D—葡萄糖—(1→2或1→4)—L—鼠李糖甙类化合物的结构进行了重新评价。
基于对10和27 HMBC谱中相应相关信号的指定，结合分析黄酮类化合物酚羟基甙化和甲基化以及异戊烯基取代的化学位移效应，本文重新评估了文献报道的脱水淫羊藿素和去甲脱水淫羊藿素甙类化合物~(13)C NMR谱中对C—5、C—7及C—4′化学位移的归属。
药理实验显示，金丝桃甙(5)具有良好的抗氧化作用；其它所获化合物生理活性的筛选正在进行中。
本文综述了淫羊藿属药用植物研究进展，近年来国内淫羊藿甙研究概况和异戊烯基黄酮在植物界的分布及生理活性。
This doctoral dissertation deals with the study on the chemical constituents of Epimedium koreanum Nakai (Berberidaceae) recorded in the Chinese Pharmacopoeia (1990), and of E. wanshanense a newly named species of the genus.
Forty four (1~44) natural products were isolated from the EtOAc extract of the aerial part of E. koreanum . On the basis of physicochemical properties and spectroscopic analyses, 2,9,10, 11,14,16,18,26,31,36 and 44 were determined to be eleven new compounds. They were named as follows: epimedokoreanone A(2); epimedokoreanin A(18),B(9),C(14) ,D(36); epimedoicarisoside A(44); caohuoside A(10), B(11), C(26), D(16) and E(31).
Sixteen (45~60) known compounds were obtained from the EtOAc and n—BuOH extract of the whole plant of E. wanshanense.
In the course of structural elucidation of the new compounds, techniques such as 2D NMR including 1H-1H COSY, 1H-13C COSY, 1H-1H TOCSY and 1H-13C long range COSY (HMBC) besides IR, UV, MS and 1D NMR, were extensively employed.
On the basis of 2D NMR spectral analyses, the disaccharide of 27 and 38, as well as 29 (58) , 30, 32(59),33(48),34,49,50,52,53,54 was confirmed as 1→2 linkage. With this set of criteria, the literatures published 3—O—L—rhamnosyl— (1→2/1→4) —L — rhamnoside, 3—O -D—xylosyl— (1→2/1→4) -L-rhamnoside and 3-O-D — glucosyl- (1 →2/1→4) —L — rhamnoside structures of anhydroicaritin and desmethylanhydroicaritin were re-evaluated.
The 13C NMR chemical shift assignments for C—5, C—7 and C—4' published in literatures for some anhydroicaritin and desmethylanhydroicaritin glycosides were re-appraised by analysing the cross—peaks in HMBC spectra of 10 and 27 and the chemical shift effects of glycosylation and methylation of phenoxyl groups and prenylation in flavonoids.
Pharmacological tests revealed that hyperoside (5) possessed marked antioxidative activity. The biological activities of other isolated compounds are currently under investigation.
Recent advances on the study of medicinal plants from the genus Epimedium, an outline on the research of icariin in China, and the resources and bioactivities of prenoid — substituted flavonoids were also reviewed.
从朝鲜淫羊藿地上部分的乙酸乙酯提取物中分离鉴定了四十四个(1～44)天然产物，其中十一个(2、9、10、11、14、16、18、26、31、36和44)为新化合物，分别命名为：朝藿酮A(2)，朝藿素A(18)、B(9)、C(14)、D(36)，朝藿甙A(10)、B(11)、C(26)、D(16)、E(31)，朝藿菲甙A(44)。
从万山淫羊藿全草的乙酸乙酯和正丁醇提取物中分离得到十六个(45～60)已知成分。
在新化合物结构鉴定过程中，除紫外、红外、质谱和一维核磁共振谱外，还充分运用了一些二维核磁共振技术，如~1H—~1H COSY、~1H—~(13)C COSY、~1H—~1H TOCSY、尤其是~1H—~(13)C long range COSY(HMBC)谱等。正是基于二维核磁共振谱分析，27、38以及29(58)、30、32(59)、33(48)、34、49、50、52、53、54的双糖被确定为1→2连接。本文以上述双糖1→2连接的光谱标准，对文献报道的脱水淫羊藿素和去甲脱水淫羊藿素3—O—L一鼠李糖—(1→2或1→4)—L—鼠李糖甙、3—O—D—木糖—(1→2或1→4)—L—鼠李糖甙及3—O—D—葡萄糖—(1→2或1→4)—L—鼠李糖甙类化合物的结构进行了重新评价。
基于对10和27 HMBC谱中相应相关信号的指定，结合分析黄酮类化合物酚羟基甙化和甲基化以及异戊烯基取代的化学位移效应，本文重新评估了文献报道的脱水淫羊藿素和去甲脱水淫羊藿素甙类化合物~(13)C NMR谱中对C—5、C—7及C—4′化学位移的归属。
药理实验显示，金丝桃甙(5)具有良好的抗氧化作用；其它所获化合物生理活性的筛选正在进行中。
本文综述了淫羊藿属药用植物研究进展，近年来国内淫羊藿甙研究概况和异戊烯基黄酮在植物界的分布及生理活性。
This doctoral dissertation deals with the study on the chemical constituents of Epimedium koreanum Nakai (Berberidaceae) recorded in the Chinese Pharmacopoeia (1990), and of E. wanshanense a newly named species of the genus.
Forty four (1~44) natural products were isolated from the EtOAc extract of the aerial part of E. koreanum . On the basis of physicochemical properties and spectroscopic analyses, 2,9,10, 11,14,16,18,26,31,36 and 44 were determined to be eleven new compounds. They were named as follows: epimedokoreanone A(2); epimedokoreanin A(18),B(9),C(14) ,D(36); epimedoicarisoside A(44); caohuoside A(10), B(11), C(26), D(16) and E(31).
Sixteen (45~60) known compounds were obtained from the EtOAc and n—BuOH extract of the whole plant of E. wanshanense.
In the course of structural elucidation of the new compounds, techniques such as 2D NMR including 1H-1H COSY, 1H-13C COSY, 1H-1H TOCSY and 1H-13C long range COSY (HMBC) besides IR, UV, MS and 1D NMR, were extensively employed.
On the basis of 2D NMR spectral analyses, the disaccharide of 27 and 38, as well as 29 (58) , 30, 32(59),33(48),34,49,50,52,53,54 was confirmed as 1→2 linkage. With this set of criteria, the literatures published 3—O—L—rhamnosyl— (1→2/1→4) —L — rhamnoside, 3—O -D—xylosyl— (1→2/1→4) -L-rhamnoside and 3-O-D — glucosyl- (1 →2/1→4) —L — rhamnoside structures of anhydroicaritin and desmethylanhydroicaritin were re-evaluated.
The 13C NMR chemical shift assignments for C—5, C—7 and C—4' published in literatures for some anhydroicaritin and desmethylanhydroicaritin glycosides were re-appraised by analysing the cross—peaks in HMBC spectra of 10 and 27 and the chemical shift effects of glycosylation and methylation of phenoxyl groups and prenylation in flavonoids.
Pharmacological tests revealed that hyperoside (5) possessed marked antioxidative activity. The biological activities of other isolated compounds are currently under investigation.
Recent advances on the study of medicinal plants from the genus Epimedium, an outline on the research of icariin in China, and the resources and bioactivities of prenoid — substituted flavonoids were also reviewed.
引文
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2．徐绥绪，王志学，吴立军，王乃利，陈英杰(1982)，中草药，13，9．
3. Oshima, Y., Okanoto, M. and Hikino, Y. (1987), Heterocycles 26,935.
4. Ito Y., Hirayama, F., Suto, K., Sagara, K. and Yishida, T. (1988) Phytochemistry 27, 911.
5. Pachaly, P., Schoncherr--weiβbarth, C. and Sin, K. K. (1990) Planta Med. 56, 277.
6. Kang. S. S., Kang, Y. J. and Lee, M. W. (1991) J. Nat. Prods. 54, 277.
7．刘崇铭，于庆海，程秀娟(1982) 中草药 13，30．
8．王敏，刘崇铭，张宝凤(1991) 沈阳药学院学报 8，272．
9．王敏，刘崇铭，张宝凤(1993) 沈阳药学院学报 10，185．
10. Moss, M. O., Tackson, R. M. and Rogers, D. (1975) Phytochemistry 14, 2706.
11. Nakahara, S., Kumatani, K. and Kameoka, H. (1975) Phytochemistry 14, 2712.
12．赵天增(1983)核磁共振氢谱，P，312．北京，北京大学出版社．
13．沈其丰(1988)核磁共振碳谱，P，96．北京，北京大学出版社．
14．中国科学院上海药物研究所编译(1981)黄酮体化合物鉴定手册，P．399，北京，科学出版社．
15．李枫，刘永隆(1988) 药学学报 23，739．
16. Mizuno M., Sakakibara, N., Hanioka, S., Iinuma, M., Tanaka, T., Liu, X. S. and Shi, D. W. (1988) Phytochemistry 26,3641.
17. Mizuno, M., Hanioka, S., Suzuki, N., Iinuma, M., Tanaka, T., Liu, X. S. and Min, Z. D. (1987) Phytochemistry 26, 861.
18. Mizuno, M., Iinuma, M.,Tanaka, T.,Sakakibara, N.,Fujikawa, T., Hanioka, S., Ishida, Y.,Liu, X. S. and Murata, H. (1988)Phytochemistry 27, 3645.
19．李枫，刘永隆(1988) 药学学报 23，672．
20．胡碧煌，周立东，刘永隆(1992) 药学学报 27，397．
21．贾世山，马超美，王建民(1990) 药学学报 25，758．
22. Harborne, J. B., Greenham, J., Williams, C. A., Eagles, J. and Markham, K. R. (1993) Phytochemistry 34,219.
23. Markham, K. R. and Chari, V. M. Carbon--13 Spectroscopy of flavonoids. In: Harborne, J. B. and Mabry, T. J. (1982) The Flavononids: Advances in Research, 1st ed, London--New York, Chapman and Hall, 19.
24. Pelter, A., Hansel, R. and Kaloga, M. (1977) Tetrahedron Lett. 51, 4547.
25．丛蒲珠(1987)质谱学在天然有机化学中的应用 P．471，北京，科学出版社．
26. Letcher, R. M. and Nhamo, L. R. (1971)J. Chem. Soc. (C)3070.
27. Miyase, T., Veno, A., Takizawa, N., Kobayashi, H. and Oguchi, H. (1988) Chem. Pharm. Bull. 36, 2475.
28. Miyase, T., Veno, A., Takizaw, N., Kobayashi, H. and Karasawa, H. (1987) Chem.??Pharm. Bull. 35, 1109.
29. Levy, G. C (1976) Topics in Carbon--13 NMR spectroscopy, Vol. 2, P. 108, New York, John Wiley and Sons. Inc.
30．沈其丰 (1988) 核磁共振碳谱，P．86，北京，北京大学出版社．
31．赵萍萍，李宝明，何丽一(1987) 药学学报 22，70．
32. Hu, B. H., Zou, L. D. and Liu, Y. L. (1992) J. Nat. Prods. 55,672.
33. Mizuno, M, Iinuma, M., Tanaka, T., Yamamoto, H. and Tu, Z. B (1991) J. Nat. Prods. 54,1427.
34. Mizuno, M., Iinuma, M., Tanaka, T. and Sakakibara, N. (1990) J. Nat. Prods. 53, 744.
35. Oshima, Y., OKamoto, M. and Hikino. H. (1989) Planta Med. 55,309.
36. Mizuno. M., Iinuma, M., Tanaka, T., Sakakibara, N., Nakanishi, T., Inada, A. and Nishi, M. (1989) Chem. Pharm. Bull. 37,2241.
37. Sherif, E. A., Gupta, R. K. and Krishmamurti, M. (1980) Tetrahedron Lett. 21,641.
38. Okuyama, T., Hosoyama,K., Hiraya, Y. and Takemoto, T. (1978) Chem. Pharm. Bull. 26, 3071.
39．姚新生(1986)黄酮类化合物．见：王宪楷主编，天然药物化学，P．308，北京，人民卫生出版社
40. Harborne, J. B. and Mabry, T. J. (1983) In" The Flavonoids: Advances in Research" P. 37, New York, Chapman and Hall.
41．李也实，刘永隆(1992) 中草药 23，8．
42. Deshpande, V. H., Pendse, A. D. and Pendse, R. (1977) Phytochemistry 15B, 205.
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