弯距翠雀花中化学成分的研究
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摘要
从弯距翠雀花(Delphinium campylocentrum Maxim．)全草提取物中分离得到13个单体化合物，并且用氢谱、碳谱、二维核磁共振谱、质谱、圆二色谱以及红外光谱对其中的11个化合物进行了鉴定，发现1个新的二萜化合物和2个新的去甲二萜生物碱，分别命名为弯翠平(campylopin)(1)以及弯翠生(campylocine)(2)和弯翠定(campylotine)(3)。其余8个已知生物碱是：delbrtmine (4)、talassimine(5)，talassamine(6)、talassimidine(7)，deltatsine(8)，delbonine(9)，dehydrodeltatsine (10)和delbruninemonoacetate(11)。弯翠平(1)为天然界中首次发现的具有hetidane型新骨架的二萜化合物。弯翠生(2)是天然界中首次发现的同时具有N-C(19)-O-C(1)氮杂缩醛和7，8-亚甲二氧基结构的牛扁碱型去甲二萜生物碱。化合物1的发现提示了一条新的海替定型二萜生物碱的生源途径假说。
Thirteen compounds were isolated from the whole herb extract from Delphinium campylocentrum Maxim, and eleven of them were elucidated clearly based on the modem spectroscopic technologies including 1D- and 2D- NMR, MS, HRMS, CD, IR, etc. In such process, one novel hetidane-type diterpene skeleton, campylopin (1), and two new norditerpenoid alkaloids, campylocine (2) and campylotine (3), along with eight known alkaloids: delbrunine (4), talassimine (5), talassamine (6), talassimidine (7), deltatsine (8), delbonine (9), dehydrodeltatsine (10), and delbrunine monoacetate (11) were firstly discovered in this plant. The discovery of compound 1 implies a new biosynthetic pathway from the atisane or hetidane-type diterpene to the hetidine-type diterpenoid alkaloid.
Thirteen compounds were isolated from the whole herb extract from Delphinium campylocentrum Maxim, and eleven of them were elucidated clearly based on the modem spectroscopic technologies including 1D- and 2D- NMR, MS, HRMS, CD, IR, etc. In such process, one novel hetidane-type diterpene skeleton, campylopin (1), and two new norditerpenoid alkaloids, campylocine (2) and campylotine (3), along with eight known alkaloids: delbrunine (4), talassimine (5), talassamine (6), talassimidine (7), deltatsine (8), delbonine (9), dehydrodeltatsine (10), and delbrunine monoacetate (11) were firstly discovered in this plant. The discovery of compound 1 implies a new biosynthetic pathway from the atisane or hetidane-type diterpene to the hetidine-type diterpenoid alkaloid.
引文
1 Wang, W. C.; Warnock, M. Flora of China, Vol. 6, Eds.: Wu, Z. Y.; Raven, P.; Hong, D. Y., Science Press, Beijing, 2001; p 223.
2 龙雅宜，张金政．蓝色花的佼佼者——翠雀与飞燕草．中国花卉盆景．2003．7．8～9
3 关文灵，李世锋．云南野生翠雀属花卉资源．亚热带植物科学．2002．31(增刊)．61-64
4 肖培根，中国毛莨科植物群的亲缘关系、化学成分和疗效间相关性的初步探索．植物分类学报，1980．18(2)．142～153
5 《全国中草药汇编》编写组．《全国中草药汇编》人民卫生出版社．1975．
6 西藏自治区卫生局、西藏军区后勤部卫生处合编．《西藏常用中草药》西藏人民出版社．1973．
7 Uiubelen, A.; Mericli, A.; Mericli, F. Insect repellent activity of diterpenoid alkaloids. Phytother. Res. 2001.15. 170～171
8 Raza, M.; Shaheen, F.; Choudhary, M. I. Anticonvulsant activities of ethanolic extract of aqueous fraction isolated from Dlephinium denudatum. J. Ethnopharm. 2001.78. 73～78
9 Raza, M.; Shaheen, F.; Choudhary, M. I. Anticonvulsant activities of the FS-1 subfraction isolated from root of Dlephinium denudatum. Phytother. Res. 2001.15.426～430
10 Zafar, S.; Aftab Ahmad, M.; Siddiqui, T. Effect of roots aqueous extract of Dlephinium denudatum on morphine-induced tolerance in mice Fitoterapia. 2002. 73. 553～556
11 Raza, M.; Shaheen, F.; Choudhary, M. I. In vitro inhibition of pentylenetetrazole and biculline-induced epileptiform activity in rat hippocampal pyramidal neurons by aqueous fraction isolated from Dlephinium denudatum. Neurosci. Lett. 2002. 333. 103～106
12 Raza, M.; Shaheen, F.; Choudhary, M. I. Inhibition of sustained repetitive firing in cultured hippocampal neurons by an aqueous fraction isolated from Dlephinium denudatum. J. Ethnopharm. 2004.90. 367～374
13 Yum, L.; Wolf, K. M.; Chiappinelli, V. A. Nicotinic acetylcholine receptors in separate brain regions exhibit different affinities for methyllycaconitine Neurosci. 1996. 72(2). 545～555
14 Davies, A. L.; Hardick, D. J.; Blagbrough, I. S. Characterisation of the binding of [~3H]methyllycaconitine: a new radioligand for labeling α7-type neuronal nicotinic acetylcholine receptors Neuropharma. 1999.38. 679～690
15 Barker, D.; Brimble, M. A.; Mcleod, M. D. Synthesis of simple analogues of methyllycaconitine-an efficient method for the preparation of the N-substituted anthranilate pharmacophore. Tetrahedron 2004. 60. 5953～5963
16 Goodall, K.; Barker, D.; Brimble, M. A review of advances in the synthesis of analogues of Delphinium alkaloid methyllyeaconitine. Synlett 2005.12. 1809～1827
17 该化合物的旋光值在D线的时候非常小，故改变了入射光的波长得到数值较大的旋光值。
18 由于化合物1的量只有5mg，故没有能形成单晶供绝对构型的确认。我们采用二位核磁共振和CD光谱对它的绝对构型进行了研究。
19 Pelletier, S. W.; Mody, N. V.; Joshi, B. S.; Schramm, L. C. In Alkaloids: Chemical and Biological Perspectives, Vol. 2, Ed.: Pelletier, S. W, John Wiley & Son Press, New York, 1984. p. 205.
20 Gonzalez, A.G.; Fuente, G. de la.; Orribo, T.; Acosta, R. D. Nevadenine and nevadensine, Two new diterpenoid alkaloids from Aconitum nevadense Vechtr. Heterocycles 1985. 23. 2979～1982.
21 Deng, W.; and Sung, W. L. Three new C_(19)-diterpenoid alkaloids, delbrunine, delbruline and delbrusine from Delphinium brunonianum Royle. Heterocycles 1986. 24(4). 873～876
22 余明新，潘远江，陈耀祖，青海翠雀化学成分的研究．有机化学．2003 23(61．563～565
23 王锋鹏，二萜生物碱的~(13)C核磁共振谱．有机化学．1982．3．161～169
24 通过和甲醇提取物的对照，我们相信从HCl提取物中分离得到的化合物1是天然产生的，而非经酸化后反应的产物。
25 Nishanov, A. A.; Sultankhodzhaev, M. N.; Yunosov, M. S.; Yusupova, I. M.; Tashkhozhaev, B. Khim. Prir. Sodein. Alkaloids of Aconitum talassicum, structure of talassamine, talassimidine, and talassimine. 1991.1.93～98
26 Joshi, B. S.; Glinski, J. A.; Chokshi, H. P.Deltatsine, a new C_(19)-diterpenoid Alkaloid from Delphinium tatsienense Franch. Heterocycles 1984. 22(9). 2037～2042
27 Shrestha, P. M.; Katz, A. Diterpenoid alkaloids from the roots of Delphinium scabriflorum. J. Nat. Prod. 2004. 67. 1574～1576
28 Jiang, Q. P.; Sung, W. L. The structures of four new diterpenoid alkaloids from Delphinium Bonvalotti Franch Heterocycles 1985.23(1). 11～15
29 Alva, A.; Grandez, M.; Madinaveita, A. Seven new norditerpenoid alkaloids from spanish Consolida orientalis Helv. Chim. Acta 2004. 87(8). 2110～2119
30 Alva, A.; Grandez, M.; Madinaveitia, A. Three new norditerpenoid alkaloids from Consolida orientalis. Chemical & Pharmaceutical Bulletin. 2004.52(5). 530～534
31 Deng, W; Sung, W. L. Three new C_(19)-diterpenoid alkaloids: delbrunine, delbruline and delbrusine from Delphinium brunonianum Royle. Heterocycles 1986. 24(4). 873～876
32 Wang, F.-P.; Liang, X.-T. The Alkaloids, Chemistry and Biology; Cordell, G. A., Ed.; Elsevier Science (USA): New York, NY, 2002; Vol. 59, p 85.
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2 龙雅宜，张金政．蓝色花的佼佼者——翠雀与飞燕草．中国花卉盆景．2003．7．8～9
3 关文灵，李世锋．云南野生翠雀属花卉资源．亚热带植物科学．2002．31(增刊)．61-64
4 肖培根，中国毛莨科植物群的亲缘关系、化学成分和疗效间相关性的初步探索．植物分类学报，1980．18(2)．142～153
5 《全国中草药汇编》编写组．《全国中草药汇编》人民卫生出版社．1975．
6 西藏自治区卫生局、西藏军区后勤部卫生处合编．《西藏常用中草药》西藏人民出版社．1973．
7 Uiubelen, A.; Mericli, A.; Mericli, F. Insect repellent activity of diterpenoid alkaloids. Phytother. Res. 2001.15. 170～171
8 Raza, M.; Shaheen, F.; Choudhary, M. I. Anticonvulsant activities of ethanolic extract of aqueous fraction isolated from Dlephinium denudatum. J. Ethnopharm. 2001.78. 73～78
9 Raza, M.; Shaheen, F.; Choudhary, M. I. Anticonvulsant activities of the FS-1 subfraction isolated from root of Dlephinium denudatum. Phytother. Res. 2001.15.426～430
10 Zafar, S.; Aftab Ahmad, M.; Siddiqui, T. Effect of roots aqueous extract of Dlephinium denudatum on morphine-induced tolerance in mice Fitoterapia. 2002. 73. 553～556
11 Raza, M.; Shaheen, F.; Choudhary, M. I. In vitro inhibition of pentylenetetrazole and biculline-induced epileptiform activity in rat hippocampal pyramidal neurons by aqueous fraction isolated from Dlephinium denudatum. Neurosci. Lett. 2002. 333. 103～106
12 Raza, M.; Shaheen, F.; Choudhary, M. I. Inhibition of sustained repetitive firing in cultured hippocampal neurons by an aqueous fraction isolated from Dlephinium denudatum. J. Ethnopharm. 2004.90. 367～374
13 Yum, L.; Wolf, K. M.; Chiappinelli, V. A. Nicotinic acetylcholine receptors in separate brain regions exhibit different affinities for methyllycaconitine Neurosci. 1996. 72(2). 545～555
14 Davies, A. L.; Hardick, D. J.; Blagbrough, I. S. Characterisation of the binding of [~3H]methyllycaconitine: a new radioligand for labeling α7-type neuronal nicotinic acetylcholine receptors Neuropharma. 1999.38. 679～690
15 Barker, D.; Brimble, M. A.; Mcleod, M. D. Synthesis of simple analogues of methyllycaconitine-an efficient method for the preparation of the N-substituted anthranilate pharmacophore. Tetrahedron 2004. 60. 5953～5963
16 Goodall, K.; Barker, D.; Brimble, M. A review of advances in the synthesis of analogues of Delphinium alkaloid methyllyeaconitine. Synlett 2005.12. 1809～1827
17 该化合物的旋光值在D线的时候非常小，故改变了入射光的波长得到数值较大的旋光值。
18 由于化合物1的量只有5mg，故没有能形成单晶供绝对构型的确认。我们采用二位核磁共振和CD光谱对它的绝对构型进行了研究。
19 Pelletier, S. W.; Mody, N. V.; Joshi, B. S.; Schramm, L. C. In Alkaloids: Chemical and Biological Perspectives, Vol. 2, Ed.: Pelletier, S. W, John Wiley & Son Press, New York, 1984. p. 205.
20 Gonzalez, A.G.; Fuente, G. de la.; Orribo, T.; Acosta, R. D. Nevadenine and nevadensine, Two new diterpenoid alkaloids from Aconitum nevadense Vechtr. Heterocycles 1985. 23. 2979～1982.
21 Deng, W.; and Sung, W. L. Three new C_(19)-diterpenoid alkaloids, delbrunine, delbruline and delbrusine from Delphinium brunonianum Royle. Heterocycles 1986. 24(4). 873～876
22 余明新，潘远江，陈耀祖，青海翠雀化学成分的研究．有机化学．2003 23(61．563～565
23 王锋鹏，二萜生物碱的~(13)C核磁共振谱．有机化学．1982．3．161～169
24 通过和甲醇提取物的对照，我们相信从HCl提取物中分离得到的化合物1是天然产生的，而非经酸化后反应的产物。
25 Nishanov, A. A.; Sultankhodzhaev, M. N.; Yunosov, M. S.; Yusupova, I. M.; Tashkhozhaev, B. Khim. Prir. Sodein. Alkaloids of Aconitum talassicum, structure of talassamine, talassimidine, and talassimine. 1991.1.93～98
26 Joshi, B. S.; Glinski, J. A.; Chokshi, H. P.Deltatsine, a new C_(19)-diterpenoid Alkaloid from Delphinium tatsienense Franch. Heterocycles 1984. 22(9). 2037～2042
27 Shrestha, P. M.; Katz, A. Diterpenoid alkaloids from the roots of Delphinium scabriflorum. J. Nat. Prod. 2004. 67. 1574～1576
28 Jiang, Q. P.; Sung, W. L. The structures of four new diterpenoid alkaloids from Delphinium Bonvalotti Franch Heterocycles 1985.23(1). 11～15
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