4-[(2S,3R,4S,5S,6S)-2-methoxy-4,5-bis(phenylmethoxy)-6-phenylmethoxycarbonyloxan-3-yl]oxy-4-oxobutanoic acid | 1192051-54-9

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 4-[(2S,3R,4S,5S,6S)-2-methoxy-4,5-bis(phenylmethoxy)-6-phenylmethoxycarbonyloxan-3-yl]oxy-4-oxobutanoic acid
• CAS: 1192051-54-9
• 化学式: C₃₂H₃₄O₁₀
• 分子量: 578.616
• InChiKey: GYNQDZORAGXWRP-PJRGDJDMSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  42
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  127
• 氢给体数：
  1
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  paclitaxel 、 4-[(2S,3R,4S,5S,6S)-2-methoxy-4,5-bis(phenylmethoxy)-6-phenylmethoxycarbonyloxan-3-yl]oxy-4-oxobutanoic acid 在 4-二甲氨基吡啶 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 为溶剂， 反应 18.0h， 以75%的产率得到
  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：

  丁二酸酐 、 3,4-bis-benzyloxy-5-hydroxy-6-methoxy-tetrahydro-pyran-2-carboxylicacid benzylester 在 吡啶 作用下， 反应 12.0h， 以96%的产率得到4-[(2S,3R,4S,5S,6S)-2-methoxy-4,5-bis(phenylmethoxy)-6-phenylmethoxycarbonyloxan-3-yl]oxy-4-oxobutanoic acid
  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.