声敏剂DEG的合成
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摘要
首次报道了声敏剂DEG的合成工艺。氯化血红素(2)在溴化氢的乙酸溶液中经脱铁及加成反应后,再与二乙二醇在浓硫酸催化下经醚化及酯化得7,12-双[1-[2-(羟基乙氧基)乙氧基]乙基]-3,8,13,17-四甲基卟啉-2,18-二丙酸二(2-羟基乙氧基)乙酯,收率83.2%。与无水乙醇经酯交换反应得7,12-双[1-[2-(羟基乙氧基)乙氧基]乙基]-3,8,13,17-四甲基卟啉-2,18-二丙酸二乙酯。然后按照先配位再水解的思路,先与四水合二氯化锰配位得锰-7,12-双[1-[2-(羟基乙氧基)乙氧基]乙基]-3,8,13,17-四甲基卟啉-2,18-二丙酸二乙酯,最后经氢氧化钠水解、盐酸酸化得目标化合物,纯度95.2%,总收率73.1%(以2计)。
The synthetic process of sonosensitizer DEG was reported in the first time. Hemin(2) was subjected to an addition and demetalation with hydrogen bromide in acetic acid, which was followed by an etherification and esterification with diethylene glycol under the catalysis of concentrated sulfuric acid to obtain di(2-hydroxyethoxy)-ethyl 7,12-bis[1-[2-(hydroxyethoxy)ethoxy]ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate in 83.2% yield.Then it reacted with anhydrous ethanol via transesterification to give diethyl 7,12-bis[1-[2-(hydroxyethoxy)ethoxy]-ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate. The latter reacted with manganese dichloride tetrahydrate via coordination to afford diethyl manganese-7,12-bis[1-[2-(hydroxyethoxy)ethoxy]ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate. Then after a hydrolysis with sodium hydroxide and an acidification with hydrochloric acid,the target compound DEG was obtained with a purity of 95.2% and an overall yield of 73.1%(based on 2).
The synthetic process of sonosensitizer DEG was reported in the first time. Hemin(2) was subjected to an addition and demetalation with hydrogen bromide in acetic acid, which was followed by an etherification and esterification with diethylene glycol under the catalysis of concentrated sulfuric acid to obtain di(2-hydroxyethoxy)-ethyl 7,12-bis[1-[2-(hydroxyethoxy)ethoxy]ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate in 83.2% yield.Then it reacted with anhydrous ethanol via transesterification to give diethyl 7,12-bis[1-[2-(hydroxyethoxy)ethoxy]-ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate. The latter reacted with manganese dichloride tetrahydrate via coordination to afford diethyl manganese-7,12-bis[1-[2-(hydroxyethoxy)ethoxy]ethyl]-3,8,13,17-tetramethyl porphyrin-2,18-dipropionate. Then after a hydrolysis with sodium hydroxide and an acidification with hydrochloric acid,the target compound DEG was obtained with a purity of 95.2% and an overall yield of 73.1%(based on 2).
引文
[1] TSURU H, SHIBAGUCHI H, KUROKI M, et al. Tumor growth inhibition by sonodynamic therapy using a novel sonosensitizer[J]. Free Radic Biol Med, 2012, 53(3):464-472.
[2] CHEN H, ZHOU X, GAO Y, et al. Recent progress in development of new sonosensitizers for sonodynamic cancer therapy[J]. Drug Discov Today, 2014, 19(4):502-509.
[3]陈俊磊,王天一,时志春,等.声敏剂DEG配体的合成及结构表征[J].高师理科学刊,2018, 38(6):46-48.
[4] XU Y, YU Q, ZHAO D, et al. Synthesis and characterization of porphyrin-based porous coordination polymers obtained by supercritical CO2 extraction[J]. J Mater Sci, 2018,53(14):10534-10542.
[5]徐士超.血红素衍生卟啉金属配合物的合成及其仿生催化应用研究[D].南京:南京理工大学硕士学位论文,2013.
[6]范开华,陈志龙,万维勤.血卟啉乙二醇醚类化合物的合成及其光动力抑瘤活性[J].中国医药工业杂志,1999,30(6):20-22.
[2] CHEN H, ZHOU X, GAO Y, et al. Recent progress in development of new sonosensitizers for sonodynamic cancer therapy[J]. Drug Discov Today, 2014, 19(4):502-509.
[3]陈俊磊,王天一,时志春,等.声敏剂DEG配体的合成及结构表征[J].高师理科学刊,2018, 38(6):46-48.
[4] XU Y, YU Q, ZHAO D, et al. Synthesis and characterization of porphyrin-based porous coordination polymers obtained by supercritical CO2 extraction[J]. J Mater Sci, 2018,53(14):10534-10542.
[5]徐士超.血红素衍生卟啉金属配合物的合成及其仿生催化应用研究[D].南京:南京理工大学硕士学位论文,2013.
[6]范开华,陈志龙,万维勤.血卟啉乙二醇醚类化合物的合成及其光动力抑瘤活性[J].中国医药工业杂志,1999,30(6):20-22.