6-O-pivaloyl-1,2:3,5-di-O-isopropylidene-α-D-glucofuranose

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 6-O-pivaloyl-1,2:3,5-di-O-isopropylidene-α-D-glucofuranose
• 英文别名: 1,2:3,5-di-O-isopropylidene-6-O-pivaloyl-α-D-glucofuranose；1,2:3,5-di-O-isopropylidene-6-O-(trimethylacetyl)α-D-glucofuranose；[(1S,2R,6R,8R,9R)-4,4,11,11-tetramethyl-3,5,7,10,12-pentaoxatricyclo[6.4.0.02,6]dodecan-9-yl]methyl 2,2-dimethylpropanoate
• 化学式: C₁₇H₂₈O₇
• 分子量: 344.405
• InChiKey: ZASDKXIHHJOAMH-UJPOAAIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-O-pivaloyl-1,2:3,5-di-O-isopropylidene-α-D-glucofuranose 在 甲醇 、 sodium methylate 作用下， 反应 24.0h， 以74.1%的产率得到1,2-3,5-di-O-isopropylidene-α-D-glucofuranose
  参考文献：
  名称：

  Glucose transporter 1-mediated vascular translocation of nanomedicines enhances accumulation and efficacy in solid tumors

  摘要：

  Nanomedicine modification with ligands directed to receptors on tumor blood vessels has the potential for selectively enhancing nanomedicine accumulation in malignant tissues by overcoming the vascular barrier of tumors. Nevertheless, the development of broadly applicable ligand approaches capable of promoting the transvascular transport of nanomedicines in a wide spectrum of tumors has been elusive so far. By considering the indispensable and persistent glycolytic fueling of tumors, we developed glucose-installed polymeric micelles loading cisplatin (Gluc-CDDP/m) targeting the glucose transporter 1 (GLUT1), which is overexpressed in most tumors and present on vascular endothelial cells, toward improving the delivery efficiency and therapeutic efficacy. The design of the glucose ligands on Gluc-CDDP/m was engineered to control the conjugation via the carbon 6 of the glucose moieties, as well as the ligand density on the poly (ethylene glycol) (PEG) shell of the micelles. The series of micelles was then studied in vitro and in vivo against GLUT1-high human squamous cell carcinoma of the head and neck OSC-19 cells and GLUT1-low human glioblastoma-astrocytoma U87MG cells. Our results showed that precisely tuning the micelles to have glucose ligands on 25% of their PEG chains increased the efficacy against the tumors by significantly enhancing the tumor accumulation, even in GLUT1-low U87MG tumors. The enhancement of the intratumoral levels of these micelles was hindered by concomitant administration of glucose, or the GLUT1 inhibitor STF-31, confirming a GLUT1/glucose-mediated increment of the accumulation. Intravital confocal laser scanning microscopy imaging of tumor tissues further demonstrated the rapid extravasation and penetration of Gluc-CDDP/m in OSC-19 tumors compared to non-targeted CDDP/m. These findings indicate GLUT1-targeting as a promising approach for overcoming the vascular barrier and boosting the delivery of nanomedicine in tumors.

  DOI：

  10.1016/j.jconrel.2019.02.021
• 作为产物：
  描述：

  3-O-[(t-butyl)dimethylsilyl]-1,2:5,6-di-O-isopropylidene-α-D-glucofuranose 在 吡啶 、 potassium fluoride 、 四丁基溴化铵 作用下， 以 水 、 乙腈 为溶剂， 反应 0.28h， 生成 6-O-pivaloyl-1,2:3,5-di-O-isopropylidene-α-D-glucofuranose
  参考文献：
  名称：

  RAPID CARBOHYDRATE PROTECTING GROUP MANIPULATIONS ASSISTED BY MICROWAVE DIELECTRIC HEATING

  摘要：

  The protocols for oligosaccharide synthesis are often tedious due to extended synthetic routes and reaction times. We herein describe methods assisted by microwave dielectric heating, which enable very short reaction times and high yields for the introduction and removal of eleven of the most commonly used protecting groups in carbohydrate syntheses. Several examples are reported, where solid supported reagents in combination with microwave dielectric heating have been used. This results in both faster and easier synthesis and purification.

  DOI：

  10.1081/car-100105712

文献信息

• RAPID CARBOHYDRATE PROTECTING GROUP MANIPULATIONS ASSISTED BY MICROWAVE DIELECTRIC HEATING
  作者：Eva Söderberg、Jacob Westman、Stefan Oscarson*

  DOI：10.1081/car-100105712

  日期：2001.6.30

  The protocols for oligosaccharide synthesis are often tedious due to extended synthetic routes and reaction times. We herein describe methods assisted by microwave dielectric heating, which enable very short reaction times and high yields for the introduction and removal of eleven of the most commonly used protecting groups in carbohydrate syntheses. Several examples are reported, where solid supported reagents in combination with microwave dielectric heating have been used. This results in both faster and easier synthesis and purification.
• Glucose transporter 1-mediated vascular translocation of nanomedicines enhances accumulation and efficacy in solid tumors
  作者：Kazumi Suzuki、Yutaka Miura、Yuki Mochida、Takuya Miyazaki、Kazuko Toh、Yasutaka Anraku、Vinicio Melo、Xueying Liu、Takehiko Ishii、Osamu Nagano、Hideyuki Saya、Horacio Cabral、Kazunori Kataoka

  DOI：10.1016/j.jconrel.2019.02.021

  日期：2019.5

  Nanomedicine modification with ligands directed to receptors on tumor blood vessels has the potential for selectively enhancing nanomedicine accumulation in malignant tissues by overcoming the vascular barrier of tumors. Nevertheless, the development of broadly applicable ligand approaches capable of promoting the transvascular transport of nanomedicines in a wide spectrum of tumors has been elusive so far. By considering the indispensable and persistent glycolytic fueling of tumors, we developed glucose-installed polymeric micelles loading cisplatin (Gluc-CDDP/m) targeting the glucose transporter 1 (GLUT1), which is overexpressed in most tumors and present on vascular endothelial cells, toward improving the delivery efficiency and therapeutic efficacy. The design of the glucose ligands on Gluc-CDDP/m was engineered to control the conjugation via the carbon 6 of the glucose moieties, as well as the ligand density on the poly (ethylene glycol) (PEG) shell of the micelles. The series of micelles was then studied in vitro and in vivo against GLUT1-high human squamous cell carcinoma of the head and neck OSC-19 cells and GLUT1-low human glioblastoma-astrocytoma U87MG cells. Our results showed that precisely tuning the micelles to have glucose ligands on 25% of their PEG chains increased the efficacy against the tumors by significantly enhancing the tumor accumulation, even in GLUT1-low U87MG tumors. The enhancement of the intratumoral levels of these micelles was hindered by concomitant administration of glucose, or the GLUT1 inhibitor STF-31, confirming a GLUT1/glucose-mediated increment of the accumulation. Intravital confocal laser scanning microscopy imaging of tumor tissues further demonstrated the rapid extravasation and penetration of Gluc-CDDP/m in OSC-19 tumors compared to non-targeted CDDP/m. These findings indicate GLUT1-targeting as a promising approach for overcoming the vascular barrier and boosting the delivery of nanomedicine in tumors.