2-[2-[2-[2-[[(3aR,5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy]ethoxy]ethoxy]ethoxy]ethanol | 937377-88-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2-[2-[2-[2-[[(3aR,5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy]ethoxy]ethoxy]ethoxy]ethanol
• CAS: 937377-88-3
• 化学式: C₂₀H₃₆O₁₀
• 分子量: 436.5
• InChiKey: DDKGHDIVAVDVIL-UYTYNIKBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  30
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  103
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  2-[2-[2-[2-[[(3aR,5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy]ethoxy]ethoxy]ethoxy]ethanol 、 silicon(IV) phthalocyanine dichloride 在 sodium hydride 作用下， 以 甲苯 为溶剂， 反应 48.0h， 以13%的产率得到
  参考文献：
  名称：

  Highly Photocytotoxic Glucosylated Silicon(IV) Phthalocyanines. Effects of Peripheral Chloro Substitution on the Photophysical and Photodynamic Properties

  摘要：

  Two novel glucoconjugated silicon(IV) phthalocyanines (compounds 3 and 4) have been prepared and examined for their photophysical and biological properties. With two axial 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose substituents linked to the silicon center through the tetraethylene glycol chain, both compounds are highly soluble and remain nonaggregated in N,N-dimethylformamide. The dichloro-substituted phthalocyanine 4 exhibits a weaker fluorescence emission and higher efficiency to generate singlet oxygen compared with the nonchlorinated counterpart 3 as a result of the heavy atom effect. Both compounds are highly photocytotoxic against HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells, particularly the nonchlorinated phthalocyanine 3, of which the IC50 values are as low as 6 nM. The lower photodynamic activity of the chlorinated derivative (IC50 = 17-21 nM) can be attributed to its higher aggregation tendency in the biological media, leading to a lower efficiency to generate reactive oxygen species inside the cells. Fluorescence microscopic studies have also revealed that compound 3 has a high and selective affinity to the lysosomes, but not the mitochondria, of HT29 cells.

  DOI：

  10.1021/jm061415j
• 作为产物：
  描述：

  四乙二醇单对甲苯磺酸酯 、 双丙酮葡萄糖 在 sodium hydride 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 以25%的产率得到2-[2-[2-[2-[[(3aR,5R,6S,6aR)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxol-6-yl]oxy]ethoxy]ethoxy]ethoxy]ethanol
  参考文献：
  名称：

  Highly Photocytotoxic Glucosylated Silicon(IV) Phthalocyanines. Effects of Peripheral Chloro Substitution on the Photophysical and Photodynamic Properties

  摘要：

  Two novel glucoconjugated silicon(IV) phthalocyanines (compounds 3 and 4) have been prepared and examined for their photophysical and biological properties. With two axial 1,2:5,6-di-O-isopropylidene-alpha-D-glucofuranose substituents linked to the silicon center through the tetraethylene glycol chain, both compounds are highly soluble and remain nonaggregated in N,N-dimethylformamide. The dichloro-substituted phthalocyanine 4 exhibits a weaker fluorescence emission and higher efficiency to generate singlet oxygen compared with the nonchlorinated counterpart 3 as a result of the heavy atom effect. Both compounds are highly photocytotoxic against HT29 human colorectal carcinoma and HepG2 human hepatocarcinoma cells, particularly the nonchlorinated phthalocyanine 3, of which the IC50 values are as low as 6 nM. The lower photodynamic activity of the chlorinated derivative (IC50 = 17-21 nM) can be attributed to its higher aggregation tendency in the biological media, leading to a lower efficiency to generate reactive oxygen species inside the cells. Fluorescence microscopic studies have also revealed that compound 3 has a high and selective affinity to the lysosomes, but not the mitochondria, of HT29 cells.

  DOI：

  10.1021/jm061415j

文献信息

• Unsymmetrical β-cyclodextrin-conjugated silicon(iv) phthalocyanines as highly potent photosensitisers for photodynamic therapy
  作者：Janet T. F. Lau、Pui-Chi Lo、Yee-Man Tsang、Wing-Ping Fong、Dennis K. P. Ng

  DOI：10.1039/c1cc13783b

  日期：——

  A series of unsymmetrical silicon(IV) phthalocyanines with a permethylated β-cyclodextrin unit and a sugar or a diamino moiety as the axial substituents have been prepared. These compounds are highly photocytotoxic with IC50 values as low as 21 nM, which is ca. sevenfold lower than those of the symmetrical bis(cyclodextrin) analogue.

  我们制备出了一系列非对称硅（IV）酞菁，其轴向取代基为过甲基化的 δ-环糊精单元和糖或二氨基。这些化合物具有很强的光毒性，其 IC50 值低至 21 nM，比对称双（环糊精）类似物的 IC50 值低约七倍。
• Effects of the number and position of the substituents on the in vitro photodynamic activities of glucosylated zinc(ii) phthalocyanines
  作者：Jian-Yong Liu、Pui-Chi Lo、Wing-Ping Fong、Dennis K. P. Ng

  DOI：10.1039/b822128f

  日期：——

  A series of mono-β-, di-α- and di-β-substituted phthalonitriles which contain one or two tetraethylene-glycol-linked 1,2:5,6-di-O-isopropylidene-α-D-glucofuranose unit(s) were prepared by typical substitution reactions. These precursors underwent self-cyclisation or mixed-cyclisation with an excess of unsubstituted phthalonitrile in the presence of Zn(OAc)2·2H2O and DBU to give the corresponding zinc(II) phthalocyanines with 1, 2 or 4 glucosylated substituent(s). For the di-α- and tetra-β-glucosylated analogues, removal of the isopropylidene groups was also performed by the treatment with trifluoroacetic acid and water to give the corresponding water-soluble deprotected glucosylated derivatives. All of these glucoconjugated phthalocyanines were fully characterised with various spectroscopic methods and studied for their photophysical properties and in vitro photodynamic activities against HT29 human colon adenocarcinoma and HepG2 human hepatocarcinoma cells. The tetra-β-glucosylated phthalocyanines ZnPc(β-PGlu)4 (4) and ZnPc(β-Glu)4 (5) were found to be essentially non-cytotoxic. By contrast, the mono- and di-glucosylated analogues ZnPc(β-PGlu) (7), ZnPc(α-PGlu)2 (11), ZnPc(α-Glu)2 (12) and ZnPc(β-PGlu)2 (20) exhibited substantial photocytotoxicity. The isopropylidene-protected di-α-substituted derivative 11 was particularly potent, having IC50 values as low as 0.03 μM. The different photodynamic activities of these compounds can be attributed to their different extent of cellular uptake and aggregation tendency in the biological media, which greatly affect their singlet oxygen generation efficiency.

  通过典型的取代反应制备了一系列单-β-、二-α-和二-β-取代的邻苯二甲酰腈，这些邻苯二甲酰腈含有一个或两个与四亚甲基乙二醇连接的 1,2:5,6-二-O-异亚丙基-α-D-呋喃葡萄糖单元。在 Zn(OAc)2-2H2O 和 DBU 的存在下，这些前体与过量的未取代酞腈进行自循环或混合循环，从而得到具有 1、2 或 4 个葡萄糖基取代基的相应锌（II）酞菁。对于二-α-和四-β-葡糖基化的类似物，也可以通过三氟乙酸和水处理来去除亚异丙基，得到相应的水溶性去保护葡糖基化衍生物。利用各种光谱方法对所有这些糖基化酞菁进行了全面表征，并研究了它们的光物理特性以及对 HT29 人结肠腺癌细胞和 HePG2 人肝癌细胞的体外光动力活性。研究发现，四-β-葡萄糖基化酞菁 ZnPc(β-PGlu)4 (4) 和 ZnPc(β-Glu)4 (5) 基本上没有细胞毒性。相比之下，单葡萄糖基化和双葡萄糖基化类似物 ZnPc(β-PGlu) (7)、ZnPc(α-PGlu)2 (11)、ZnPc(α-Glu)2 (12) 和 ZnPc(β-PGlu)2 (20) 则表现出很大的光细胞毒性。异亚丙基保护的二α-取代衍生物 11 尤其有效，其 IC50 值低至 0.03 μM。这些化合物不同的光动力活性可归因于它们在生物介质中不同的细胞吸收程度和聚集倾向，这在很大程度上影响了它们产生单线态氧的效率。