benzoic acid 4-(8-benzyloxy-6-methoxy-2-phenyl-hexahydropyrano[3,2-d][1,3]dioxin-7-yloxy)-butyl ester | 1092536-31-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡喃二恶英
• 英文名称: benzoic acid 4-(8-benzyloxy-6-methoxy-2-phenyl-hexahydropyrano[3,2-d][1,3]dioxin-7-yloxy)-butyl ester
• 英文别名: 4-[[(2R,4aR,6S,7R,8S,8aR)-6-methoxy-2-phenyl-8-phenylmethoxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-7-yl]oxy]butyl benzoate
• CAS: 1092536-31-6
• 化学式: C₃₂H₃₆O₈
• 分子量: 548.633
• InChiKey: QVKQIHHDENHHLY-MAGZYXQKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  81.7
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  benzoic acid 4-(8-benzyloxy-6-methoxy-2-phenyl-hexahydropyrano[3,2-d][1,3]dioxin-7-yloxy)-butyl ester 在 sodium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 1.5h， 以100%的产率得到4-[[(2R,4aR,6S,7R,8S,8aR)-6-methoxy-2-phenyl-8-phenylmethoxy-4,4a,6,7,8,8a-hexahydropyrano[3,2-d][1,3]dioxin-7-yl]oxy]butan-1-ol
  参考文献：
  名称：

  Targeting the Delivery of Glycan-Based Paclitaxel Prodrugs to Cancer Cells via Glucose Transporters

  摘要：

  This report describes the synthesis of four novel paclitaxel based prodrugs with glycan conjugation (1-4). Glycans were conjugated using an ester or ether bond as the linker between 2'-paclitaxel and the 2'-glucose or glucuronic acid moiety. These prodrugs showed good water solubility and selective cytotoxicity against cancer cell lines, but showed reduced toxicity toward normal cell lines and cancer cell lines with low expression levels of GLUTs. The ester conjugated prodrug 1 showed the most cytotoxicity among the prodrugs examined and could be transported into cells via GLUTs. Fluorescent and confocal microscopy demonstrated that targeted cells exhibited morphological changes in tubulin and chromosomal alterations that were similar to those observed with paclitaxel treatment. Therefore, these glycan-based prodrugs may be good drug candidates for cancer therapy, and the glycan conjugation approach is an alternative method to enhance the targeted delivery of other drugs to cancer cells that overexpress GLUTs.

  DOI：

  10.1021/jm8006257
• 作为产物：
  描述：

  4-溴丁基苯甲酸酯 、 methyl 4,6-O-benzylidene-3-O-benzyl-α-D-glucopyranoside 在 四丁基碘化铵 、 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 36.0h， 以73.3%的产率得到benzoic acid 4-(8-benzyloxy-6-methoxy-2-phenyl-hexahydropyrano[3,2-d][1,3]dioxin-7-yloxy)-butyl ester
  参考文献：
  名称：

  Targeting the Delivery of Glycan-Based Paclitaxel Prodrugs to Cancer Cells via Glucose Transporters

  摘要：

  This report describes the synthesis of four novel paclitaxel based prodrugs with glycan conjugation (1-4). Glycans were conjugated using an ester or ether bond as the linker between 2'-paclitaxel and the 2'-glucose or glucuronic acid moiety. These prodrugs showed good water solubility and selective cytotoxicity against cancer cell lines, but showed reduced toxicity toward normal cell lines and cancer cell lines with low expression levels of GLUTs. The ester conjugated prodrug 1 showed the most cytotoxicity among the prodrugs examined and could be transported into cells via GLUTs. Fluorescent and confocal microscopy demonstrated that targeted cells exhibited morphological changes in tubulin and chromosomal alterations that were similar to those observed with paclitaxel treatment. Therefore, these glycan-based prodrugs may be good drug candidates for cancer therapy, and the glycan conjugation approach is an alternative method to enhance the targeted delivery of other drugs to cancer cells that overexpress GLUTs.

  DOI：

  10.1021/jm8006257

文献信息

• Targeting the Delivery of Glycan-Based Paclitaxel Prodrugs to Cancer Cells via Glucose Transporters
  作者：Yih-Shyan Lin、Rudeewan Tungpradit、Supachok Sinchaikul、Feng-Ming An、Der-Zen Liu、Suree Phutrakul、Shui-Tein Chen

  DOI：10.1021/jm8006257

  日期：2008.12.11

  This report describes the synthesis of four novel paclitaxel based prodrugs with glycan conjugation (1-4). Glycans were conjugated using an ester or ether bond as the linker between 2'-paclitaxel and the 2'-glucose or glucuronic acid moiety. These prodrugs showed good water solubility and selective cytotoxicity against cancer cell lines, but showed reduced toxicity toward normal cell lines and cancer cell lines with low expression levels of GLUTs. The ester conjugated prodrug 1 showed the most cytotoxicity among the prodrugs examined and could be transported into cells via GLUTs. Fluorescent and confocal microscopy demonstrated that targeted cells exhibited morphological changes in tubulin and chromosomal alterations that were similar to those observed with paclitaxel treatment. Therefore, these glycan-based prodrugs may be good drug candidates for cancer therapy, and the glycan conjugation approach is an alternative method to enhance the targeted delivery of other drugs to cancer cells that overexpress GLUTs.