methyl 2-(6-(4-(tert-butoxy)-4-oxobutoxy)-3-oxo-3H-xanthen-9-yl)benzoate | 1227413-23-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: methyl 2-(6-(4-(tert-butoxy)-4-oxobutoxy)-3-oxo-3H-xanthen-9-yl)benzoate
• CAS: 1227413-23-1
• 化学式: C₂₉H₂₈O₇
• 分子量: 488.537
• InChiKey: OXAOHWWTIVKFNL-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.85
• 重原子数：
  36.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  92.04
• 氢给体数：
  0.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  methyl 2-(6-(4-(tert-butoxy)-4-oxobutoxy)-3-oxo-3H-xanthen-9-yl)benzoate 在 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 以89%的产率得到4-((9-(2-(methoxycarbonyl)phenyl)-3-oxo-3H-xanthen-6-yl)oxy)butanoic acid
  参考文献：
  名称：

  Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release

  摘要：

  An efficient mechanism-based tumor-targeting drug delivery system. based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drug delivery system is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface and (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized. i.e., receptor-mediated endocytosis of the conjugate, drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3, and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, hearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed), and W138 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drug delivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein at to the taxoid) against the same three cell lines was confirmed. This mechanism-based to drug delivery system will find a range of applications.

  DOI：

  10.1021/bc9005656
• 作为产物：
  描述：

  4-羟基丁酸叔丁酯 、 荧光素甲酯 在 偶氮二甲酸二异丙酯 、 三苯基膦 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 3.0h， 以85%的产率得到methyl 2-(6-(4-(tert-butoxy)-4-oxobutoxy)-3-oxo-3H-xanthen-9-yl)benzoate
  参考文献：
  名称：

  Mechanism-Based Tumor-Targeting Drug Delivery System. Validation of Efficient Vitamin Receptor-Mediated Endocytosis and Drug Release

  摘要：

  An efficient mechanism-based tumor-targeting drug delivery system. based on tumor-specific vitamin-receptor mediated endocytosis, has been developed. The tumor-targeting drug delivery system is a conjugate of a tumor-targeting molecule (biotin: vitamin H or vitamin B-7), a mechanism-based self-immolative linker and a second-generation taxoid (SB-T-1214) as the cytotoxic agent. This conjugate (1) is designed to be (i) specific to the vitamin receptors overexpressed on tumor cell surface and (ii) internalized efficiently through receptor-mediated endocytosis, followed by smooth drug release via glutathione-triggered self-immolation of the linker. In order to monitor and validate the sequence of events hypothesized. i.e., receptor-mediated endocytosis of the conjugate, drug release, and drug-binding to the target protein (microtubules), three fluorescent/fluorogenic molecular probes (2, 3, and 4) were designed and synthesized. The actual occurrence of these processes was unambiguously confirmed by means of confocal fluorescence microscopy (CFM) and flow cytometry using L1210FR leukemia cells, overexpressing biotin receptors. The molecular probe 4, hearing the taxoid linked to fluorescein, was also used to examine the cell specificity (i.e., efficacy of receptor-based cell targeting) for three cell lines, L1210FR (biotin receptors overexpressed), L1210 (biotin receptors not overexpressed), and W138 (normal human lung fibroblast, biotin receptor negative). As anticipated, the molecular probe 4 exhibited high specificity only to L1210FR. To confirm the direct correlation between the cell-specific drug delivery and anticancer activity of the probe 4, its cytotoxicity against these three cell lines was also examined. The results clearly showed a good correlation between the two methods. In the same manner, excellent cell-specific cytotoxicity of the conjugate 1 (without fluorescein at to the taxoid) against the same three cell lines was confirmed. This mechanism-based to drug delivery system will find a range of applications.

  DOI：

  10.1021/bc9005656