(3aR,6aR)-4-hydroxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-2-one | 1308889-69-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (3aR,6aR)-4-hydroxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-2-one
• CAS: 1308889-69-1
• 化学式: C₅H₆O₅
• 分子量: 146.1
• InChiKey: MZJQVDURTGUCLV-HERZVMAMSA-N

物化性质

• 沸点：
  451.4±45.0 °C(Predicted)
• 密度：
  1.631±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  10
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  65
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (3aR,6aR)-4-hydroxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-2-one 在 三乙胺 作用下， 以 甲醇 为溶剂， 生成 D-erythrofuranose
  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 palladium on activated charcoal 、 氢气 作用下， 以82%的产率得到(3aR,6aR)-4-hydroxy-3a,4,6,6a-tetrahydrofuro[3,4-d][1,3]dioxol-2-one
  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。
• Synthesis and Evaluation of Noviose Replacements on Novobiocin That Manifest Antiproliferative Activity
  作者：Huiping Zhao、Bhaskar Reddy Kusuma、Brian S. J. Blagg

  DOI：10.1021/ml100070r

  日期：2010.10.14

  Structural modifications to the coumarin core and benzamide side chain of novobiocin have successfully transformed the natural product from a selective DNA gyrase inhibitor into a potent inhibitor of the Hsp90 C-terminus. However, no structure−activity relationship studies have been conducted on the noviose appendage, which represents the rate-limiting synthon in the preparation of analogues. Therefore

  对新生霉素的香豆素核心和苯甲酰胺侧链的结构修饰已成功将天然产物从选择性 DNA 促旋酶抑制剂转化为 Hsp90 C 端的有效抑制剂。然而，没有对 noviose 附属物进行构效关系研究，它代表了类似物制备中的限速合成子。因此，合成并评估了一系列糖模拟物和非糖衍生物，以鉴定表现出 Hsp90 抑制作用的简化化合物。对两种乳腺癌细胞系的评估表明，用简化的烷基胺替代立体化学复合物 noviose 增加了抗增殖活性，导致新生霉素类似物的 IC 50值在中纳摩尔范围内。
• Development of Noviomimetics as C-Terminal Hsp90 Inhibitors
  作者：Mercy Anyika、Mason McMullen、Leah K. Forsberg、Rick T. Dobrowsky、Brian S. J. Blagg

  DOI：10.1021/acsmedchemlett.5b00331

  日期：2016.1.14

  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.