(3R)-3-((triisopropylsilyl)oxy)tetrahydrofuran-2-ol | 1308889-72-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氧唑烯
• 英文名称: (3R)-3-((triisopropylsilyl)oxy)tetrahydrofuran-2-ol
• CAS: 1308889-72-6
• 化学式: C₁₃H₂₈O₃Si
• 分子量: 260.449
• InChiKey: WBLPACJOWKASGQ-PZORYLMUSA-N

物化性质

• 沸点：
  301.0±42.0 °C(Predicted)
• 密度：
  0.95±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.29
• 重原子数：
  17.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  38.69
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (3R)-3-((triisopropylsilyl)oxy)tetrahydrofuran-2-ol 在 四丁基氟化铵 作用下， 生成 (3R)-oxolane-2,3-diol
  参考文献：
  名称：

  Development of Noviomimetics as C-Terminal Hsp90 Inhibitors

  摘要：

  KU-32 and KU-596 are novobiocin-derived, C terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.

  DOI：

  10.1021/acsmedchemlett.5b00331
• 作为产物：
  描述：

  在 二异丁基氢化铝 作用下， 以89%的产率得到(3R)-3-((triisopropylsilyl)oxy)tetrahydrofuran-2-ol
  参考文献：
  名称：

  Development of Noviomimetics as C-Terminal Hsp90 Inhibitors

  摘要：

  KU-32 and KU-596 are novobiocin-derived, C terminal heat shock protein 90 (Hsp90) modulators that induce Hsp70 levels and manifest neuroprotective activity. However, the synthetically complex noviose sugar requires 10 steps to prepare, which makes translational development difficult. In this study, we developed a series of "noviomimetic" analogues of KU-596, which contain noviose surrogates that can be easily prepared, while maintaining the ability to induce Hsp70 levels. Both sugar and sugar analogues were designed, synthesized, and evaluated in a luciferase reporter assay, which identified compound 37, a benzyl containing noviomimetic, as the most potent inducer of Hsp70.

  DOI：

  10.1021/acsmedchemlett.5b00331

文献信息

• Engineering an Antibiotic to Fight Cancer: Optimization of the Novobiocin Scaffold to Produce Anti-proliferative Agents
  作者：Huiping Zhao、Alison C. Donnelly、Bhaskar R. Kusuma、Gary E. L. Brandt、Douglas Brown、Roger A. Rajewski、George Vielhauer、Jeffrey Holzbeierlein、Mark S. Cohen、Brian S. J. Blagg

  DOI：10.1021/jm200148p

  日期：2011.6.9

  Development of the DNA gyrase inhibitor, novobiocin, into a selective Hsp90 inhibitor was accomplished through structural modifications to the amide side chain, coumarin ring, and sugar moiety. These species exhibit ∼700-fold improved anti-proliferative activity versus the natural product as evaluated by cellular efficacies against breast, colon, prostate, lung, and other cancer cell lines. Utilization

  通过对酰胺侧链、香豆素环和糖部分的结构修饰，将 DNA 促旋酶抑制剂新生霉素开发为选择性 Hsp90 抑制剂。与天然产物相比，这些物种的抗增殖活性提高了约 700 倍，正如通过对乳腺癌、结肠癌、前列腺癌、肺癌和其他癌细胞系的细胞功效所评估的那样。利用为三个新生霉素合成子建立的结构-活性关系产生了优化的支架，其表现出针对一组癌细胞系的中纳摩尔活性，并作为通过 Hsp90 抑制表现出其活性的先导化合物。