一年蓬有效成分的结构修饰研究
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摘要
一年蓬[Erigeron annuus(L).Pers]是飞蓬属植物一年蓬的全草及根,全草可入药,具有治疗疟疾的功效,主治消化不良、肠炎、传染性肝炎、淋巴结炎、血尿等。焦袂康酸和飞蓬苷为吡喃酮类化合物,在飞蓬属植物中广泛存在,并且具有显著增加脑血管血流量,改善脑血循环,降低脑血管阻力,提高血脑屏障的通透性,增加心肌营养回流的作用,还具备提高机体巨噬细胞免疫功能和较强的抑制内凝血等作用。
对焦袂康酸的制备方法进行了研究,最终确定了以5倍量95%乙醇回流提取一年蓬药材,对乙酸乙酯部分和正丁醇部分进行硅胶柱分离为最佳制备方法,得到的焦袂康酸占药材干重的0.5%。该法制备焦袂康酸具有产率高、操作简单、溶剂消耗少、节约时间等特点。
本研究以焦袂康酸为起始原料,把3,4,5-三甲氧基肉桂酸、阿魏酸、烟酸和阿司匹林各自制备成酰氯后与焦袂康酸进行酯化反应,得到4个化合物,并通过紫外光谱(UV),质谱(ESI-MS和ESI-TOF-MS)及核磁共振波谱(1H-NMR、13C-NMR、HMQC、HMBC)等现代波谱学方法技术,鉴定了它们的结构,确定为目标化合物,经SCIFINDER查询,均为新化合物。
本研究应用OSIRIS Property Explorer系统对焦袂康酸,四种羧酸进行测算,并且对四个新化合物进行了活性模拟测算。评价提示:4个新化合物均有希望成为治疗药物。这为进一步进行药理活性研究提供了依据,为设计焦袂康酸衍生物提供了思路。
Erigeron annuus is whole plant with roots of Erigeron annuus(L).Pers of genus Erigeron, whole plant can be used as medicine, which has the effect of treatment of malaria, it is the main treatment of dyspepsia, enteritis, infectious hepatitis, lymphadenitis, hematuria and so on. Pyromeconic acid and erigeroside belong to the pyrone compounds, widely exist in the Erigeron plant, and have a significant increase in cerebral blood flow, improve blood circulation and reduce cerebral vascular resistance, increase blood-brain barrier permeability, increase nutrient return of myocardial function, also have to improve the body immune function of macrophages and a strong role in the inhibition of coagulation.
The present research has conducted the research to the preparation method of pyromeconic acid, ultimately determine the amount of 5 times of 95% ethanol reflux and extract herbs three times, carry on the silica gel column separation to ethyl acetate extract and n-butanol extract as the best preparation, get pyromeconic acid accounted for 0.5% of the dry weight of herbs. The preparation method of pyromeconic acid with high yield, simple operation, low solvent consumption, saving time and so on.
In this research, pyromeconic acid as the starting material, the 3,4,5 - trimethoxy cinnamic acid, ferulic acid, nicotinic acid and aspirin were prepared as acyl chloride respectively and carries on the esterification with pyromeconic acid, get four compounds, by ultraviolet spectrum(UV),mass spectrum (ESI-MS and ESI-TOF-MS) and nuclear magnetic resonance spectrum (1H-NMR, 13C-NMR, HMQC, HMBC) spectrum and other modern methods and techniques, identification of their structures, determine that they are the target compounds, after SCIFINDER inquiry, they are the new compounds.
In this research, applied OSIRIS Property Explorer system to measure and calculate pyromeconic acid and four kinds of acid, and the active simulation of the four new compounds were measured and calculated. Assessment tips: four new compounds hopefully become the therapeutic drug. This study provides the basis for further pharmacology research, provides the guideline for further design the preparation of pyromeconic acid derivatives.
对焦袂康酸的制备方法进行了研究,最终确定了以5倍量95%乙醇回流提取一年蓬药材,对乙酸乙酯部分和正丁醇部分进行硅胶柱分离为最佳制备方法,得到的焦袂康酸占药材干重的0.5%。该法制备焦袂康酸具有产率高、操作简单、溶剂消耗少、节约时间等特点。
本研究以焦袂康酸为起始原料,把3,4,5-三甲氧基肉桂酸、阿魏酸、烟酸和阿司匹林各自制备成酰氯后与焦袂康酸进行酯化反应,得到4个化合物,并通过紫外光谱(UV),质谱(ESI-MS和ESI-TOF-MS)及核磁共振波谱(1H-NMR、13C-NMR、HMQC、HMBC)等现代波谱学方法技术,鉴定了它们的结构,确定为目标化合物,经SCIFINDER查询,均为新化合物。
本研究应用OSIRIS Property Explorer系统对焦袂康酸,四种羧酸进行测算,并且对四个新化合物进行了活性模拟测算。评价提示:4个新化合物均有希望成为治疗药物。这为进一步进行药理活性研究提供了依据,为设计焦袂康酸衍生物提供了思路。
Erigeron annuus is whole plant with roots of Erigeron annuus(L).Pers of genus Erigeron, whole plant can be used as medicine, which has the effect of treatment of malaria, it is the main treatment of dyspepsia, enteritis, infectious hepatitis, lymphadenitis, hematuria and so on. Pyromeconic acid and erigeroside belong to the pyrone compounds, widely exist in the Erigeron plant, and have a significant increase in cerebral blood flow, improve blood circulation and reduce cerebral vascular resistance, increase blood-brain barrier permeability, increase nutrient return of myocardial function, also have to improve the body immune function of macrophages and a strong role in the inhibition of coagulation.
The present research has conducted the research to the preparation method of pyromeconic acid, ultimately determine the amount of 5 times of 95% ethanol reflux and extract herbs three times, carry on the silica gel column separation to ethyl acetate extract and n-butanol extract as the best preparation, get pyromeconic acid accounted for 0.5% of the dry weight of herbs. The preparation method of pyromeconic acid with high yield, simple operation, low solvent consumption, saving time and so on.
In this research, pyromeconic acid as the starting material, the 3,4,5 - trimethoxy cinnamic acid, ferulic acid, nicotinic acid and aspirin were prepared as acyl chloride respectively and carries on the esterification with pyromeconic acid, get four compounds, by ultraviolet spectrum(UV),mass spectrum (ESI-MS and ESI-TOF-MS) and nuclear magnetic resonance spectrum (1H-NMR, 13C-NMR, HMQC, HMBC) spectrum and other modern methods and techniques, identification of their structures, determine that they are the target compounds, after SCIFINDER inquiry, they are the new compounds.
In this research, applied OSIRIS Property Explorer system to measure and calculate pyromeconic acid and four kinds of acid, and the active simulation of the four new compounds were measured and calculated. Assessment tips: four new compounds hopefully become the therapeutic drug. This study provides the basis for further pharmacology research, provides the guideline for further design the preparation of pyromeconic acid derivatives.
引文
[1] Li X,Pan J,GAO K. Pharmazie,2006,61(5):474-477.
[2]张人伟,杨生元,林詠月.灯盏花的化学成分研究Ⅰ.焦袂康酸及一种新甙的分离、鉴定.药学学报,1981,16(1):68-69.
[3]张印俊,李良琼,杨培全,等.多舌飞蓬甙的分离和结构.药学学报,1998,33(11):836-838.
[4] Imai. Yakugzku Zasshi,1954,74:109-110.
[5] Talapatra SK,Chakravarti R,Talapatoa B. Indian J Chem Sect B,1979,17B(3):298-299.
[6] Proksa B. Chemical Papers,1991,45(6):837-844.
[7] Werner H,Sljbramaniam SP. Phytochemistry,1971,10(7):1689-1690.
[8] Imai,Tsuneo. JP28004942,1953.
[9] Ost H. J Prakt Chem,1897,19(2):177.
[10] Stenhouse J. Ann Chem,1844,49:18.
[11] Borsche W. Ber,1916,49:2544.
[12] Garkusha G. Zh Obshch Khim,1953,23:1578.
[13] Kukolja. Croatica Chemica Acta,1961,33:229-233.
[14] Atkinson,George F,Itzkovitch IJ. Analytica Chimica Acta,1970,49(1):195-198.
[15] JP42011586,1967.
[16] Robiqnet M. Ann Chem,1833,5:102.
[17] Peratoner A,Leone H. Gazz Chim Ital,1994,24Ⅱ:79.
[18] Belonosov IS,Konstantinova AA. Zh Prikl Khim,1952,25:1233-1236.
[19] Shono T,Matsumura Y. Tetrahedron Lett,1976,17(17):1363-1364.
[20] Sigeru T,TANAKA H,ANODA T,etc. Chemistry Lett,1976,(5):495-498.
[21] Weeks PD,Kuhla DE,Allingham RP,etc. Carbohydr Res,1977,56:195-199.
[22] Weeks PD,Brennan TM,Brannegan DP,etc. J Org Chem,1980,45:1109-1113.
[23] Tate BE,Miller RL. US3130204,1964.
[24] Liu ZD,Khodr HH,Liu DY,etc. J Med Chem,1999,42:4814-4823.
[25]胡昌奇,程彰华,关玲.飞蓬甙的全合成和对微循环障碍的初步观察.药学学报,1988,23(10):786-788.
[26]周耘,张卫东,顾正兵,等.灯盏花苷的全合成研究.中国药物化学杂志,2002,12(2):68-72.
[27]沙靖全,于文锦,李锦州,等.焦袂康酸新工艺合成的研究.化学与粘合,2002, 2:83-85.
[28]李明,沈连刚,王建新.焦袂康酸的合成工艺研究.化学世界,2005,46(12):749-751.
[29] Ellis BL,Duhme AK,Hider RC. J Med Chem,1996,39:3659-3670.
[30] Dehmlow EV,Westerheide R. Heterocycles,1994,37(1):355-366.
[31] Chittenden CJF. Carbohydr Res,1969,11:424.
[32] Mayer,Roland. Chemische Berichte,1957,90:2369-2372.
[33] Hosoya S,Komatsu N,Hara N. Japanese Journal of Experimental Medicine,1952,22:303-312.
[34] Imai,Tsuneo. JP28004942,1953.
[35]孙汉董,岳建明,陈玉馨,等.焦袂康酸及其葡萄糖甙(飞蓬甙)在制药中的应用.CN1136435,1996.
[36] Takemura M,Inazu Y. Ann Rept Takamine Lab,1953,5:114-118.
[37] Ghisalberti,Carlo. WO2001017497,2001.
[38] JP57134409,1982.
[39] JP57137394,1982.
[40] JP56112482,1981.
[41] Hale. US2690388,1954.
[42] Yang CT,Sreerama SG,Hsieh WY,etc. Inorganic Chemistry,2008,47(7):2719-2727.
[43] Merck Index 13th.
[44]梁娜,孙少平,罗跃娥,等.阿魏酸的研究进展.黑龙江中医药,2009,(3):39-40.
[45]欧仕益,包惠燕,蓝志东.阿魏酸及其衍生物的药理作用研究进展.中药材,2001,24(3):220-221.
[46]邹凯华,张华.阿司匹林的研究进展.上海医药,2009,30(2):64-66.
[47]郑艳斌,印杰,钱莉敏.阿司匹林临床应用新进展.上海医药,2004,25(6):273-274.
[48]王奇昌,白金全,郭丰艳,等.烟酸制备的研究进展.广东化工,2008,35(3):32-35.
[49] CCD2004:Combined Chemical Dictionary 2004 edition.
[50]徐娟,王林.血管扩张药桂哌齐特的合成研究.中国新药杂志,2003,12(8): 625-626.
[51]张晓霞,韩培红.马来酸桂哌齐特的药理作用及临床应用研究.中国药房,2007,18(26):2060-2062.
[52]彭司勋.药物化学进展(4).化学工业出版社,2005,1-22.
[53] Hiroyuka N,Yutaka S,Hiroko S. Chem Pharm Bull,1982,30(12): 4554-4556.
[54]熊晓云,邹永,刘毅,等.系列烟酸前体药物的合成.中国药物化学杂志,2002,9(2):86-89.
[55] Ponchiroli,Osvaldo. EP0080229,1983.
[56] AIST: Integrated Spectral Database System of Organic Compounds.
[57]张博,孙佳明,常仁龙,等.辽藁本化学成分研究.中药材,2009,32(5):710-712.
[58]李微,陈发奎,尹相武,等.大青叶的化学成分.沈阳药科大学学报,2005,22(1):15-17.
[2]张人伟,杨生元,林詠月.灯盏花的化学成分研究Ⅰ.焦袂康酸及一种新甙的分离、鉴定.药学学报,1981,16(1):68-69.
[3]张印俊,李良琼,杨培全,等.多舌飞蓬甙的分离和结构.药学学报,1998,33(11):836-838.
[4] Imai. Yakugzku Zasshi,1954,74:109-110.
[5] Talapatra SK,Chakravarti R,Talapatoa B. Indian J Chem Sect B,1979,17B(3):298-299.
[6] Proksa B. Chemical Papers,1991,45(6):837-844.
[7] Werner H,Sljbramaniam SP. Phytochemistry,1971,10(7):1689-1690.
[8] Imai,Tsuneo. JP28004942,1953.
[9] Ost H. J Prakt Chem,1897,19(2):177.
[10] Stenhouse J. Ann Chem,1844,49:18.
[11] Borsche W. Ber,1916,49:2544.
[12] Garkusha G. Zh Obshch Khim,1953,23:1578.
[13] Kukolja. Croatica Chemica Acta,1961,33:229-233.
[14] Atkinson,George F,Itzkovitch IJ. Analytica Chimica Acta,1970,49(1):195-198.
[15] JP42011586,1967.
[16] Robiqnet M. Ann Chem,1833,5:102.
[17] Peratoner A,Leone H. Gazz Chim Ital,1994,24Ⅱ:79.
[18] Belonosov IS,Konstantinova AA. Zh Prikl Khim,1952,25:1233-1236.
[19] Shono T,Matsumura Y. Tetrahedron Lett,1976,17(17):1363-1364.
[20] Sigeru T,TANAKA H,ANODA T,etc. Chemistry Lett,1976,(5):495-498.
[21] Weeks PD,Kuhla DE,Allingham RP,etc. Carbohydr Res,1977,56:195-199.
[22] Weeks PD,Brennan TM,Brannegan DP,etc. J Org Chem,1980,45:1109-1113.
[23] Tate BE,Miller RL. US3130204,1964.
[24] Liu ZD,Khodr HH,Liu DY,etc. J Med Chem,1999,42:4814-4823.
[25]胡昌奇,程彰华,关玲.飞蓬甙的全合成和对微循环障碍的初步观察.药学学报,1988,23(10):786-788.
[26]周耘,张卫东,顾正兵,等.灯盏花苷的全合成研究.中国药物化学杂志,2002,12(2):68-72.
[27]沙靖全,于文锦,李锦州,等.焦袂康酸新工艺合成的研究.化学与粘合,2002, 2:83-85.
[28]李明,沈连刚,王建新.焦袂康酸的合成工艺研究.化学世界,2005,46(12):749-751.
[29] Ellis BL,Duhme AK,Hider RC. J Med Chem,1996,39:3659-3670.
[30] Dehmlow EV,Westerheide R. Heterocycles,1994,37(1):355-366.
[31] Chittenden CJF. Carbohydr Res,1969,11:424.
[32] Mayer,Roland. Chemische Berichte,1957,90:2369-2372.
[33] Hosoya S,Komatsu N,Hara N. Japanese Journal of Experimental Medicine,1952,22:303-312.
[34] Imai,Tsuneo. JP28004942,1953.
[35]孙汉董,岳建明,陈玉馨,等.焦袂康酸及其葡萄糖甙(飞蓬甙)在制药中的应用.CN1136435,1996.
[36] Takemura M,Inazu Y. Ann Rept Takamine Lab,1953,5:114-118.
[37] Ghisalberti,Carlo. WO2001017497,2001.
[38] JP57134409,1982.
[39] JP57137394,1982.
[40] JP56112482,1981.
[41] Hale. US2690388,1954.
[42] Yang CT,Sreerama SG,Hsieh WY,etc. Inorganic Chemistry,2008,47(7):2719-2727.
[43] Merck Index 13th.
[44]梁娜,孙少平,罗跃娥,等.阿魏酸的研究进展.黑龙江中医药,2009,(3):39-40.
[45]欧仕益,包惠燕,蓝志东.阿魏酸及其衍生物的药理作用研究进展.中药材,2001,24(3):220-221.
[46]邹凯华,张华.阿司匹林的研究进展.上海医药,2009,30(2):64-66.
[47]郑艳斌,印杰,钱莉敏.阿司匹林临床应用新进展.上海医药,2004,25(6):273-274.
[48]王奇昌,白金全,郭丰艳,等.烟酸制备的研究进展.广东化工,2008,35(3):32-35.
[49] CCD2004:Combined Chemical Dictionary 2004 edition.
[50]徐娟,王林.血管扩张药桂哌齐特的合成研究.中国新药杂志,2003,12(8): 625-626.
[51]张晓霞,韩培红.马来酸桂哌齐特的药理作用及临床应用研究.中国药房,2007,18(26):2060-2062.
[52]彭司勋.药物化学进展(4).化学工业出版社,2005,1-22.
[53] Hiroyuka N,Yutaka S,Hiroko S. Chem Pharm Bull,1982,30(12): 4554-4556.
[54]熊晓云,邹永,刘毅,等.系列烟酸前体药物的合成.中国药物化学杂志,2002,9(2):86-89.
[55] Ponchiroli,Osvaldo. EP0080229,1983.
[56] AIST: Integrated Spectral Database System of Organic Compounds.
[57]张博,孙佳明,常仁龙,等.辽藁本化学成分研究.中药材,2009,32(5):710-712.
[58]李微,陈发奎,尹相武,等.大青叶的化学成分.沈阳药科大学学报,2005,22(1):15-17.
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