1,2,3,4-tetra-O-acetyl-6-sulfamoyl-β-D-glucopyranose | 1268376-43-7

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: 1,2,3,4-tetra-O-acetyl-6-sulfamoyl-β-D-glucopyranose
• 英文别名: 1,2,3,4-Tetra-O-acetyl-6-sulfamoyl-beta-D-glucopyranose；[(2R,3R,4S,5R,6S)-4,5,6-triacetyloxy-2-(sulfamoyloxymethyl)oxan-3-yl] acetate
• CAS: 1268376-43-7
• 化学式: C₁₄H₂₁NO₁₂S
• 分子量: 427.386
• InChiKey: QDAXJNRNUATRQE-RKQHYHRCSA-N

物化性质

• 沸点：
  511.8±60.0 °C(Predicted)
• 密度：
  1.46±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.5
• 重原子数：
  28
• 可旋转键数：
  11
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  192
• 氢给体数：
  1
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  1,2,3,4-tetra-O-acetyl-6-sulfamoyl-β-D-glucopyranose 在 sodium methylate 作用下， 以 甲醇 为溶剂， 生成 6-sulfamoyl-α-D-glucopyranose 、 6-sulfamoyl-β-D-glucopyranose
  参考文献：
  名称：

  Design, Synthesis, and Biological Evaluation of Novel Carbohydrate-Based Sulfamates as Carbonic Anhydrase Inhibitors

  摘要：

  Carbonic anhydrases (CAs) IX and XII are enzymes with newly validated potential for the development of personalized, first-in-class cancer chemotherapies. Here we present the design and synthesis of novel carbohydrate-based CA inhibitors, several of which were very efficient inhibitors (K-i < 10 nM) with good selectivity for cancer-associated CA isozymes over off-target CA isozymes. All inhibitors comprised a carbohydrate core with one hydroxyl group derivatized as a sulfamate. Five different carbohydrates were chosen to present a selection of molecular shapes with subtle stereochernical differences to the CA enzymes active site. Variable modifications of the remaining sugar hydroxyl groups were incorporated to provide an incremental coverage of chemical property parameters that are associated with biopharmaceutical performance. All sulfamate inhibitors displayed ligand efficiencies that are consistent with those reported for good drug lead candidates.

  DOI：

  10.1021/jm101525j
• 作为产物：
  描述：

  1,2,3,4-四-O-乙酰基-β-D-葡萄吡喃糖 在 吡啶 、 1,1,1,3,3,3-hexafluoropropan-2-yl sulfamate 作用下， 以 二氯甲烷 为溶剂， 反应 18.0h， 以84%的产率得到1,2,3,4-tetra-O-acetyl-6-sulfamoyl-β-D-glucopyranose
  参考文献：
  名称：

  六氟异丙基氨基磺酸盐：合成氨基磺酸盐和磺酰胺的有用试剂

  摘要：

  氨基磺酸盐和磺酰胺最经常是由醇和胺与氨磺酰氯合成的，氨磺酰氯是不稳定的试剂。我们已经确定六氟异丙基氨基磺酸盐（HFIPS）是一种稳定的固体，在温和的反应条件下，它很容易与多种醇，胺，酚和苯胺反应。反应的唯一副产物是六氟异丙醇（HFIP），在进行水后处理（可选）并通过蒸发除去溶剂后，通常可以高纯度分离反应产物。

  DOI：

  10.1021/acs.orglett.1c00855

文献信息

• Promiscuity of Carbonic Anhydrase II. Unexpected Ester Hydrolysis of Carbohydrate-Based Sulfamate Inhibitors
  作者：Marie Lopez、Hoan Vu、Conan K. Wang、Maarten G. Wolf、Gerrit Groenhof、Alessio Innocenti、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/ja207855c

  日期：2011.11.16

  of electrospray ionization-Fourier transform ion cyclotron resonance-mass spectrometry (ESI-FTICR-MS), we observed directly the sequential loss of all four acyl groups from one of the carbohydrate-based sulfamates. For this compound, the inhibitor and substrate binding mode were further analyzed using free energy calculations. These calculations suggested that the parent compound binds almost exclusively

  碳酸酐酶 (CA) 是一种酶，其内源性反应是 CO(2) 的可逆水合作用，生成 HCO(3)(-) 和一个质子。还已知 CA 对活化酯表现出微弱且混杂的酯酶活性。在这里，我们报告了用一组 CA 抑制剂获得的一系列发现，这些发现非常出人意料地表明这些化合物既是 CO(2) 水合抑制剂，也是 CA 酯酶活性的底物。这些化合物包含一个单糖核心，其中 C-6 伯羟基被衍生为氨基磺酸盐（用于 CA 识别）。剩余的四个糖羟基被酰化。使用蛋白质 X 射线晶体学，获得了与四种氨基磺酸盐抑制剂复合的人 CA II 的晶体结构。正如预期的那样，这四种结构显示出典型的 CA 蛋白-氨基磺酸盐相互作用。出乎意料的是，在异头中心 (C-1) 而非母体 C-1 酰基处观察到游离羟基。此外，这个羟基在碳水化合物环的轴向上被观察到，而在母体结构中它是赤道的。提出了一种解释立体化学反转的机制。对于三种抑制剂，C-2 或 C-2
• Hexafluoroisopropyl Sulfamate: A Useful Reagent for the Synthesis of Sulfamates and Sulfamides
  作者：Matthew A. Sguazzin、Jarrod W. Johnson、Jakob Magolan

  DOI：10.1021/acs.orglett.1c00855

  日期：2021.5.7

  Sulfamates and sulfamides are most often synthesized from alcohols and amines with sulfamoyl chloride, which is an unstable reagent. We have identified hexafluoroisopropyl sulfamate (HFIPS) as a bench-stable solid that reacts readily with a wide variety of alcohols, amines, phenols, and anilines under mild reaction conditions. The sole byproduct of the reaction is hexafluoroisopropanol (HFIP) and reaction

  氨基磺酸盐和磺酰胺最经常是由醇和胺与氨磺酰氯合成的，氨磺酰氯是不稳定的试剂。我们已经确定六氟异丙基氨基磺酸盐（HFIPS）是一种稳定的固体，在温和的反应条件下，它很容易与多种醇，胺，酚和苯胺反应。反应的唯一副产物是六氟异丙醇（HFIP），在进行水后处理（可选）并通过蒸发除去溶剂后，通常可以高纯度分离反应产物。
• Design, Synthesis, and Biological Evaluation of Novel Carbohydrate-Based Sulfamates as Carbonic Anhydrase Inhibitors
  作者：Marie Lopez、Jonathan Trajkovic、Laurent F. Bornaghi、Alessio Innocenti、Daniela Vullo、Claudiu T. Supuran、Sally-Ann Poulsen

  DOI：10.1021/jm101525j

  日期：2011.3.10

  Carbonic anhydrases (CAs) IX and XII are enzymes with newly validated potential for the development of personalized, first-in-class cancer chemotherapies. Here we present the design and synthesis of novel carbohydrate-based CA inhibitors, several of which were very efficient inhibitors (K-i < 10 nM) with good selectivity for cancer-associated CA isozymes over off-target CA isozymes. All inhibitors comprised a carbohydrate core with one hydroxyl group derivatized as a sulfamate. Five different carbohydrates were chosen to present a selection of molecular shapes with subtle stereochernical differences to the CA enzymes active site. Variable modifications of the remaining sugar hydroxyl groups were incorporated to provide an incremental coverage of chemical property parameters that are associated with biopharmaceutical performance. All sulfamate inhibitors displayed ligand efficiencies that are consistent with those reported for good drug lead candidates.