留兰香水溶性部分化学成分的研究
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摘要
留兰香为唇形科薄荷属植物留兰香(Mentha spicata L)的全草。其味辛、甘,性微温,具有和中理气、祛风散寒、消炎、止血、收敛之功效,用于治疗伤风感冒、胃气痛、鼻衄、目赤、疗疮热疥等症。历代本草对留兰香记述不多但均有提及。另外,根据我们前期的药效学研究结果,留兰香具有抗炎、止痛、抗溃疡、抗菌、抗病毒的功效。
本研究是以“863国家重大科技专项——二类新药留兰香软胶囊治疗重症痔疮”的研究与开发为基础,以抗炎活性为指导,对留兰香水溶性部分进行了化学成分的研究,采用甲基化的方法处理水溶性部分样品以降低其极性,并应用萃取技术、大孔树脂D101、硅胶柱色谱、葡聚糖凝胶(Sephadex LH-20)色谱等多种分离手法对留兰香水溶性部分经甲基化后的化学成分进行了分离,共获得15个单体成分,通过理化性质和波谱数据分析(~1H-NMR、~(13)C-NMR)并结合文献,鉴定了其中13个化合物的结构,分别为:柠檬酸三甲酯(trimethyl citrate,1)、原儿茶酸甲酯(methyl protocatechuate,2)、香草酸甲酯(methyl vanillate,3)、次黄嘌呤核苷(inosine,4)、尿苷(uridine,5)、胡萝卜苷(daucosterol,6)、香草醛(vanillin,7)、4-羟基苯甲酸正丁酯(n-butyl-4-hydroxybenzoate,8)、紫云英苷(astragalin,9)、丁香苷(syringin,10)、腺苷(adenosine,11)、芦丁(rutin,12)、槲皮素-3-O-β-D-吡喃葡萄糖苷(quercetin-3-O-β-D-pyranoglucoside,13)。将化合物1、2和3还原为有机酸,依次为柠檬酸(citric acid,1′)、原儿茶酸(protocatechuic acid,2′)、香草酸(vanillic acid,3′),并经高效液相色谱验证这三个化合物均为甲基化后的产物。以上化合物1′、2′、3′及4-13中,化合物4、5和11为首次从薄荷属植物中分离得到的己知化合物;化合物1′、7-10、12-13为首次从留兰香中分离得到的已知化合物。
本研究的意义在于:首次采用甲基化的化学转化方法来降低留兰香水溶性部分的极性,并利用多种色谱分离方法明确了甲基化产物的化学成分,进而发现了留兰香中更多的活性单体成分,也为后继开发提供了物质基础。
Mentha spicata L.belongs to the genus Mentha(Lamiaceae),which tastes pungent and sweet, and its natural character is a little warm.This plant has used to treat cold,peratodynia,rhinitis and furunculosis dieases,and it also showed the anti-inflammatory,hemostatic and pain-relieving properties by our previous work.
Based on the previous work and guided by its bioactive results,the water-soluble fraction was dealt with the methylation method for reducing its polarity,then the products were isolated by silica gel column chromatography,macroporous resin D 101,Sephadex LH-20 and so on.Fifteen compounds were isolated and their structures were identified by physical and chemical characters and spectroscopic analysis(~1H-NMR,~(13)C-NMR).Thirteen compounds were elucidated as trimethyl citrate(1),methyl protocatechuate(2),methyl vanillate(3),inosine(4),uridine(5),daucosterol(6), vanillin(7),n-butyl-4-hydroxybenzoate(8),astragalin(9),syringin(10),adenosine(11),rutin(12), quercetin-3-O-β-D-pyranoglucoside(13).Respectively,among them,compound 1,2 and 3 were reverted and give to citric acid(1'),protocatechuic acid(2'),vanillic acid(3').Compounds 1-3 were proved to be the products of menthylation by means of HPLC analysis.So compound 1',2',3' and from 4 to 13,compound 4,5 and 11 were firstly isolated from the Mentha.genus,and compound 1', 7—10,12—13 were isolated from this plant for the first time.
The menthylation reaction was firstly used to reduce the polarity of water-soluble fraction of Mentha spicata L.Many compounds were obtained from this methylated fraction.This result will helpful to confirm the natural basis of Mentha spicata L.for its bioactivities.
本研究是以“863国家重大科技专项——二类新药留兰香软胶囊治疗重症痔疮”的研究与开发为基础,以抗炎活性为指导,对留兰香水溶性部分进行了化学成分的研究,采用甲基化的方法处理水溶性部分样品以降低其极性,并应用萃取技术、大孔树脂D101、硅胶柱色谱、葡聚糖凝胶(Sephadex LH-20)色谱等多种分离手法对留兰香水溶性部分经甲基化后的化学成分进行了分离,共获得15个单体成分,通过理化性质和波谱数据分析(~1H-NMR、~(13)C-NMR)并结合文献,鉴定了其中13个化合物的结构,分别为:柠檬酸三甲酯(trimethyl citrate,1)、原儿茶酸甲酯(methyl protocatechuate,2)、香草酸甲酯(methyl vanillate,3)、次黄嘌呤核苷(inosine,4)、尿苷(uridine,5)、胡萝卜苷(daucosterol,6)、香草醛(vanillin,7)、4-羟基苯甲酸正丁酯(n-butyl-4-hydroxybenzoate,8)、紫云英苷(astragalin,9)、丁香苷(syringin,10)、腺苷(adenosine,11)、芦丁(rutin,12)、槲皮素-3-O-β-D-吡喃葡萄糖苷(quercetin-3-O-β-D-pyranoglucoside,13)。将化合物1、2和3还原为有机酸,依次为柠檬酸(citric acid,1′)、原儿茶酸(protocatechuic acid,2′)、香草酸(vanillic acid,3′),并经高效液相色谱验证这三个化合物均为甲基化后的产物。以上化合物1′、2′、3′及4-13中,化合物4、5和11为首次从薄荷属植物中分离得到的己知化合物;化合物1′、7-10、12-13为首次从留兰香中分离得到的已知化合物。
本研究的意义在于:首次采用甲基化的化学转化方法来降低留兰香水溶性部分的极性,并利用多种色谱分离方法明确了甲基化产物的化学成分,进而发现了留兰香中更多的活性单体成分,也为后继开发提供了物质基础。
Mentha spicata L.belongs to the genus Mentha(Lamiaceae),which tastes pungent and sweet, and its natural character is a little warm.This plant has used to treat cold,peratodynia,rhinitis and furunculosis dieases,and it also showed the anti-inflammatory,hemostatic and pain-relieving properties by our previous work.
Based on the previous work and guided by its bioactive results,the water-soluble fraction was dealt with the methylation method for reducing its polarity,then the products were isolated by silica gel column chromatography,macroporous resin D 101,Sephadex LH-20 and so on.Fifteen compounds were isolated and their structures were identified by physical and chemical characters and spectroscopic analysis(~1H-NMR,~(13)C-NMR).Thirteen compounds were elucidated as trimethyl citrate(1),methyl protocatechuate(2),methyl vanillate(3),inosine(4),uridine(5),daucosterol(6), vanillin(7),n-butyl-4-hydroxybenzoate(8),astragalin(9),syringin(10),adenosine(11),rutin(12), quercetin-3-O-β-D-pyranoglucoside(13).Respectively,among them,compound 1,2 and 3 were reverted and give to citric acid(1'),protocatechuic acid(2'),vanillic acid(3').Compounds 1-3 were proved to be the products of menthylation by means of HPLC analysis.So compound 1',2',3' and from 4 to 13,compound 4,5 and 11 were firstly isolated from the Mentha.genus,and compound 1', 7—10,12—13 were isolated from this plant for the first time.
The menthylation reaction was firstly used to reduce the polarity of water-soluble fraction of Mentha spicata L.Many compounds were obtained from this methylated fraction.This result will helpful to confirm the natural basis of Mentha spicata L.for its bioactivities.
引文
[1]郑健,高慧媛,陈广通,等.留兰香的活性成分(Ⅰ).沈阳药科大学学报.2006,23(3):145-147.
[2]郑健,高慧媛,陈广通,等.留兰香的活性成分(Ⅱ).沈阳药科大学学报.2006,23(4):212-215.
[3]陈广通,高慧媛,郑健,等.留兰香活性部位化学成分的研究Ⅲ.中国中药杂志.2006,31(7):560-562.
[4]郑健,赵冬升,吴斌,等.留兰香中化学成分的分离与鉴定.中国中药杂志.2002,27(10):749-751.
[5]郑健.留兰香活性成分研究.沈阳药科大学博士学位论文.
[6]Jian Zheng,Guangtong Chen,Huiyuan Gao,et al.Two new lignans from Mentha spicata L.Journal of Asian Natural Products Research 2007,9(5),445-449.
[7]Jian Zheng,Li-jin Wu,Lu Zheng,et al.Two new monoterpenoid glycosides from Mentha spicata L.Journal of Asian Natural Products Research 2003,5(1),69-73.
[8]刘绍华.“801”留兰香精油化学成分的研究.广西植物.1997,17(3):286-288.
[9]叶兰荣,姚雷,徐勇,等.四种薄荷植物学性状和精油成分的比较.上海交通大学学报(农业科学版).2006,24(5):435-440.
[10]周自新,剑桂新.心叶留兰香的挥发油成分.植物资源与环境.1995,4(3):63-64.
[11]陈静威,吴振,闫鹏飞,等.留兰香挥发油化学成分的研究.哈尔滨商业大学学报(自然科学版).2003,19(1):72-74.
[12]刘绍华,覃青云,杨卫豪,等.“Scotch”留兰香精油化学成分分析.中草药.2005,36(4):505-506.
[13]许鹏翔,贾卫民,毕良武,等.一种变种留兰香精油化学成分的研究.香料香精化妆品.2003,4:14-16.
[14]河璞,康占国.留兰香的生产应用.河南农业.2004,8:21.
[15]吕世明,谭艾娟.留兰香的抗炎作用研究.中兽医医药杂志.2001,5:3-4.
[16]李宏.205薄荷属植物及其精油的质量标准与药学应用.国外医药·植物药分册.2000,15(4):146-151.
[17]药理学教研组.中草药芳香油对呼吸系统作用的初步研究.浙江医科大学学报.1979,8(2):71-77.
[18]唐法娣,谢强敏,王砚,等.葛缕酮的气道扩张作用和呼吸道抗过敏作用.中国药理学通报.1999,15(3):235-237.
[19]Hong-Bin Sun,Ruimao Hua,Yingwu Yin.ZrOCl2·8H20:An Efficient,Cheap and Reusable Catalyst for the Esterification of Acrylic Acid and Other Carboxylic Acids with Equimolar Amounts of Alcohols.Molecules,2006,11:263-271.
[20]邵萌,杨跃辉,高慧媛,等.金荞麦中的酚酸类成分.中国中药杂志.2005,30(20):1591-1593.
[21]许向前,洪文荣,陈代杰,等.麦角菌HCB-01712生物合成香草酸甲酯.中国抗生素杂志.2006,31(12):743-745.
[22]吴皓,李伟,张科卫,等.半夏药材鉴别成分的研究.中国中药杂志.2003,28(9):836-839.
[23]HU Xiaoyan,DOU Deqiang,PEI Yuping,et al.Chemical Constituents of Roots of Ranunculus ternatus Thunb.Journal of Chinese Pharmaceutical Sciences,2006,15(2):127-129.
[24]段礼新,余正江,冯宝民,等.复方三子养亲汤中酚酸类成分.沈阳药科大学学报.2007,(11):679-681.
[25]胡喜兰,朱慧,刘存瑞,等.凤仙花的化学成分研究.中成药.2003,25(10):833-834.
[26]于德泉.分析化学手册:第五分册.北京:化学工业出版社.1989,823-824.
[27]冯育林,李运秋,徐丽珍,等.蜀葵花的化学成分研究(Ⅱ)——黄酮类成分研究.中草药.2006,37(11):1622-1624.
[28]LIU Dai-lin,PANG Fa-gen,ZHANG Xue,et al.Water-soluble phenolic glycosides from the whole plant of Bulbophyllum odoratissimum.Acta Pharmaceutica S inica,2006,41(8):738-741.
[29]XUE Pei-feng,LIANG Hong,WANG Bin,et al.Chemical Constituents from Potentilla multifida L.Journal of Chinese Pharmaceutical Sciences,2005,14(2):86-88.
[30]马挺军,屠鹏飞,吕飞杰,等.土贝母的化学成分研究.中国药学杂志.2007,42(13):981-983.
[31]王梦月,卫莹芳,李晓波.荨麻抗风湿活性部位的化学成分研究.中草药.2006,37(9):1300-1303.
[32]刘承先.对甲苯磺酸催化合成苯甲酸丙酯.化学工程师.2005,7:13-14.
[33]程定海,山桂云,李述燕.水杨酸甲酯的合成研究.西华师范大学学报(自然科学版).2004,25(4):434-436.
[34]胡俐萍,周芸,徐满才.1—氮杂—2—甲氧基—1—环庚烯的无溶剂合成.精细化工中间体.2006,36(5):30-31.
[35]张劲,阳年发,汤卫军,等.对二甲氨基苯甲酸的合成研究.化学试剂.2003,25(4):245-246.
[36]季卫刚,李欣.邻苯二酚甲基化合成愈创木酚.化学研究.2002,13(1):25-26.
[37]李波,许时婴.难溶于二甲亚砜多糖的甲基化方法研究.天然产物研究与开发.2004,16(3):207-209.
[38]董群,方积年.寡糖及多糖甲基化方法的发展及现状.天然产物研究与开发.1995,7(2):60-64.
[39]吴立军主编.天然药物化学.第四版.北京:人民卫生出版社.2003,166.
[40]张德娟.浅析有机反应中浓硫酸的催化作用.中学化学.2003,1:17-18.
[2]郑健,高慧媛,陈广通,等.留兰香的活性成分(Ⅱ).沈阳药科大学学报.2006,23(4):212-215.
[3]陈广通,高慧媛,郑健,等.留兰香活性部位化学成分的研究Ⅲ.中国中药杂志.2006,31(7):560-562.
[4]郑健,赵冬升,吴斌,等.留兰香中化学成分的分离与鉴定.中国中药杂志.2002,27(10):749-751.
[5]郑健.留兰香活性成分研究.沈阳药科大学博士学位论文.
[6]Jian Zheng,Guangtong Chen,Huiyuan Gao,et al.Two new lignans from Mentha spicata L.Journal of Asian Natural Products Research 2007,9(5),445-449.
[7]Jian Zheng,Li-jin Wu,Lu Zheng,et al.Two new monoterpenoid glycosides from Mentha spicata L.Journal of Asian Natural Products Research 2003,5(1),69-73.
[8]刘绍华.“801”留兰香精油化学成分的研究.广西植物.1997,17(3):286-288.
[9]叶兰荣,姚雷,徐勇,等.四种薄荷植物学性状和精油成分的比较.上海交通大学学报(农业科学版).2006,24(5):435-440.
[10]周自新,剑桂新.心叶留兰香的挥发油成分.植物资源与环境.1995,4(3):63-64.
[11]陈静威,吴振,闫鹏飞,等.留兰香挥发油化学成分的研究.哈尔滨商业大学学报(自然科学版).2003,19(1):72-74.
[12]刘绍华,覃青云,杨卫豪,等.“Scotch”留兰香精油化学成分分析.中草药.2005,36(4):505-506.
[13]许鹏翔,贾卫民,毕良武,等.一种变种留兰香精油化学成分的研究.香料香精化妆品.2003,4:14-16.
[14]河璞,康占国.留兰香的生产应用.河南农业.2004,8:21.
[15]吕世明,谭艾娟.留兰香的抗炎作用研究.中兽医医药杂志.2001,5:3-4.
[16]李宏.205薄荷属植物及其精油的质量标准与药学应用.国外医药·植物药分册.2000,15(4):146-151.
[17]药理学教研组.中草药芳香油对呼吸系统作用的初步研究.浙江医科大学学报.1979,8(2):71-77.
[18]唐法娣,谢强敏,王砚,等.葛缕酮的气道扩张作用和呼吸道抗过敏作用.中国药理学通报.1999,15(3):235-237.
[19]Hong-Bin Sun,Ruimao Hua,Yingwu Yin.ZrOCl2·8H20:An Efficient,Cheap and Reusable Catalyst for the Esterification of Acrylic Acid and Other Carboxylic Acids with Equimolar Amounts of Alcohols.Molecules,2006,11:263-271.
[20]邵萌,杨跃辉,高慧媛,等.金荞麦中的酚酸类成分.中国中药杂志.2005,30(20):1591-1593.
[21]许向前,洪文荣,陈代杰,等.麦角菌HCB-01712生物合成香草酸甲酯.中国抗生素杂志.2006,31(12):743-745.
[22]吴皓,李伟,张科卫,等.半夏药材鉴别成分的研究.中国中药杂志.2003,28(9):836-839.
[23]HU Xiaoyan,DOU Deqiang,PEI Yuping,et al.Chemical Constituents of Roots of Ranunculus ternatus Thunb.Journal of Chinese Pharmaceutical Sciences,2006,15(2):127-129.
[24]段礼新,余正江,冯宝民,等.复方三子养亲汤中酚酸类成分.沈阳药科大学学报.2007,(11):679-681.
[25]胡喜兰,朱慧,刘存瑞,等.凤仙花的化学成分研究.中成药.2003,25(10):833-834.
[26]于德泉.分析化学手册:第五分册.北京:化学工业出版社.1989,823-824.
[27]冯育林,李运秋,徐丽珍,等.蜀葵花的化学成分研究(Ⅱ)——黄酮类成分研究.中草药.2006,37(11):1622-1624.
[28]LIU Dai-lin,PANG Fa-gen,ZHANG Xue,et al.Water-soluble phenolic glycosides from the whole plant of Bulbophyllum odoratissimum.Acta Pharmaceutica S inica,2006,41(8):738-741.
[29]XUE Pei-feng,LIANG Hong,WANG Bin,et al.Chemical Constituents from Potentilla multifida L.Journal of Chinese Pharmaceutical Sciences,2005,14(2):86-88.
[30]马挺军,屠鹏飞,吕飞杰,等.土贝母的化学成分研究.中国药学杂志.2007,42(13):981-983.
[31]王梦月,卫莹芳,李晓波.荨麻抗风湿活性部位的化学成分研究.中草药.2006,37(9):1300-1303.
[32]刘承先.对甲苯磺酸催化合成苯甲酸丙酯.化学工程师.2005,7:13-14.
[33]程定海,山桂云,李述燕.水杨酸甲酯的合成研究.西华师范大学学报(自然科学版).2004,25(4):434-436.
[34]胡俐萍,周芸,徐满才.1—氮杂—2—甲氧基—1—环庚烯的无溶剂合成.精细化工中间体.2006,36(5):30-31.
[35]张劲,阳年发,汤卫军,等.对二甲氨基苯甲酸的合成研究.化学试剂.2003,25(4):245-246.
[36]季卫刚,李欣.邻苯二酚甲基化合成愈创木酚.化学研究.2002,13(1):25-26.
[37]李波,许时婴.难溶于二甲亚砜多糖的甲基化方法研究.天然产物研究与开发.2004,16(3):207-209.
[38]董群,方积年.寡糖及多糖甲基化方法的发展及现状.天然产物研究与开发.1995,7(2):60-64.
[39]吴立军主编.天然药物化学.第四版.北京:人民卫生出版社.2003,166.
[40]张德娟.浅析有机反应中浓硫酸的催化作用.中学化学.2003,1:17-18.