水溶性葛根素衍生物的合成
|
摘要
以葛根素为起始原料,分别经亲核取代反应和羟甲基化反应得到水溶性4′-羟乙基葛根素和3′,5′-二羟甲基葛根素,对首次得到的3′,5′-二羟甲基葛根素,用正交实验对的合成条件进行了优化,当n(葛根素)∶n(甲醛)∶n(氢氧化钠)=1∶2∶4,反应温度为60℃,反应时间为4.0 h,产率为69.0%。目标化合物的结构经IR、~1H NMR、~(13)C NMR和元素分析方法进行表征。经测试4′-羟乙基葛根素和3′,5′-二羟甲基葛根素水溶性分别是葛根素的5倍和10倍。
Water-soluble 4′-hydroxyethyl puerarin and 3′,5′-dihydroxymethyl puerarin were synthesized by nucleophilic substitution and hydroxymethylation respectively from puerarin as raw materials.The optimum synthetic conditions of 3′,5′-dihydroxymethyl puerarin was studied for the first time by the four factors and three levels orthogonal experiment.The optimal mole ratio was n(puerarin)∶n(methanal)∶n(sodium hydroxide)=1∶2∶4,the reaction temperature 60℃ and the reaction time 4 h.The yield under the optimum conditions was up to 69.0%.The target molecules was characterized by IR,~1H NMR,~(13)C NMR spectra and elemental analysis.The water solubility of 4′-hydroxyethyl puerarin and 3′,5′-dihydroxymethyl puerarin were 5 times and 10 times that of puerarin.
Water-soluble 4′-hydroxyethyl puerarin and 3′,5′-dihydroxymethyl puerarin were synthesized by nucleophilic substitution and hydroxymethylation respectively from puerarin as raw materials.The optimum synthetic conditions of 3′,5′-dihydroxymethyl puerarin was studied for the first time by the four factors and three levels orthogonal experiment.The optimal mole ratio was n(puerarin)∶n(methanal)∶n(sodium hydroxide)=1∶2∶4,the reaction temperature 60℃ and the reaction time 4 h.The yield under the optimum conditions was up to 69.0%.The target molecules was characterized by IR,~1H NMR,~(13)C NMR spectra and elemental analysis.The water solubility of 4′-hydroxyethyl puerarin and 3′,5′-dihydroxymethyl puerarin were 5 times and 10 times that of puerarin.
引文
[1]欧明洪.葛根素的药理作用及临床应用[J].中国药业,2000,12:59-60.
[2]Yeung D,Leung S,Xu Y C.Puerarin,an isoflavonoid derived from Radix puerariae,potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery.[J].Eur J Pharmacol,2006,552(1):105–111.
[3]吴燕红,苏子仁,陈建南,等.从小鼠体内血药浓度时间曲线与组织分布特征评价葛根素的给药途径[J].中药新药与临床药理,2005,16(2):112-115.
[4]张峻.190例葛根素注射液不良反应分析[J].广州医药,2003,34(5):55-56.
[5]李琳,李少华.葛根素注射液临床疗效评价[J].中华新医学,2005,6(3):345-347.
[6] 张尊听,陈莉莉.白杨素衍生物的合成和晶体结构及与DNA的作用[J].药学学报,2007,42(5):492-496.
[2]Yeung D,Leung S,Xu Y C.Puerarin,an isoflavonoid derived from Radix puerariae,potentiates endothelium-independent relaxation via the cyclic AMP pathway in porcine coronary artery.[J].Eur J Pharmacol,2006,552(1):105–111.
[3]吴燕红,苏子仁,陈建南,等.从小鼠体内血药浓度时间曲线与组织分布特征评价葛根素的给药途径[J].中药新药与临床药理,2005,16(2):112-115.
[4]张峻.190例葛根素注射液不良反应分析[J].广州医药,2003,34(5):55-56.
[5]李琳,李少华.葛根素注射液临床疗效评价[J].中华新医学,2005,6(3):345-347.
[6] 张尊听,陈莉莉.白杨素衍生物的合成和晶体结构及与DNA的作用[J].药学学报,2007,42(5):492-496.