diethyl (2S,3R)-(+)-erythro-2-hydroxy-3-bromosuccinate | 80640-15-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: diethyl (2S,3R)-(+)-erythro-2-hydroxy-3-bromosuccinate
• 英文别名: (2R,3R)-diethyl 2-bromo-3-hydroxysuccinate；diethyl (2R,3R)-2-bromo-3-hydroxybutanedioate
• CAS: 80640-15-9
• 化学式: C₈H₁₃BrO₅
• 分子量: 269.092
• InChiKey: XVMUUAOSLJEHMN-RITPCOANSA-N

物化性质

• 溶解度：
  可溶于乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  14
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  diethyl (2S,3R)-(+)-erythro-2-hydroxy-3-bromosuccinate 在 草酰氯 、 氨 、 potassium carbonate 、 potassium hydroxide 作用下， 以 乙醇 、 二氯甲烷 、 丙酮 为溶剂， 生成 (2S,3S)-3-aminocarbonyl-2-ethoxycarbonyloxirane
  参考文献：
  名称：

  接近生物活性反式环氧琥珀酰胺基团的实验电子密度模型-取代基效应与晶体堆积

  摘要：

  所述反式-epoxysuccinyl酰胺基如半胱氨酸蛋白酶抑制剂的生物学活性部分，如酸loxistatin E64c已被用作用于对相对于它们的生物活性的小的活性成分的电子密度的环境影响的理论研究的基准系统。在此，据报道，尽可能小的活性位点模型化合物的合成和电子性能弥合了反式环氧琥珀酰酰胺的未知实验电子密度与相关药物的众所周知功能之间的差距。分子内取代基效应与分子间晶体堆积效应对电子密度的影响是分开的，这使我们能够预测对电子密度进行实验性电子研究的条件。反式环氧琥珀酰胺是可能的。在这种情况下，通过模型能量分析的新工具揭示了羧酸化合物在模型化合物中对于晶体堆积和生物活性的特殊重要性。

  DOI：

  10.1002/poc.3683
• 作为产物：
  描述：

  diethyl (2S,3R)-erythro-2-acetoxy-3-bromosuccinate 在 氢溴酸 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 反应 4.0h， 生成 diethyl (2S,3R)-(+)-erythro-2-hydroxy-3-bromosuccinate
  参考文献：
  名称：

  立体选择性合成δ-multistriatin旋光形式，欧洲小榆树皮甜菜引诱欧洲人群

  摘要：

  立体选择性合成高度旋光纯的δ-multistriatin[（1 S，2 S，4 S，5 R）-2,4-二甲基-5-乙基-6，8-二氧杂双环[3.2.1）辛烷及其对映体从酒石酸对映体开始制备“对映体”。

  DOI：

  10.1016/0040-4020(80)85029-0

文献信息

• An Improved Preparation of the Activity-Based Probe JPM-OEt and In Situ Applications
  作者：Matthew Bogyo、Kareem A. Chehade、Amos Baruch、Steven H. Verhelst

  DOI：10.1055/s-2004-837295

  日期：——

  A short, stereoselective synthesis of the general, cell permeable cathepsin probe JPM-OEt, is presented. The synthetic route is improved and described in more detail than previous reports for related compounds. This serves as a facile method for the synthesis of multi-gram quantities of activity-based probes utilizing an epoxide-succinyl scaffold. Additionally, JPM-OEt is shown to be cell permeable, allowing in vivo characterization of cysteine proteases. More importantly, this reagent has recently been shown to be an effective general inhibitor of papain family cysteine proteases in animal models of cancer. For this reason the outlined synthesis method will enable future in vivo studies using this reagent.

  本文介绍了一种通用的、可渗透细胞的胰蛋白酶探针 JPM-OEt 的简短立体选择性合成方法。与之前有关相关化合物的报道相比，该合成路线得到了改进和更详细的描述。这是一种利用环氧化物-琥珀酰支架合成多克活性探针的简便方法。此外，JPM-OEt 还具有细胞渗透性，可以在体内鉴定半胱氨酸蛋白酶。更重要的是，这种试剂最近在癌症动物模型中被证明是一种有效的木瓜蛋白酶家族半胱氨酸蛋白酶通用抑制剂。因此，概述的合成方法将有助于今后使用这种试剂进行体内研究。
• Cysteine protease inhibitors and uses thereof
  申请人：The Trustees of Columbia University in the City of New York

  公开号：US09403843B2

  公开（公告）日：2016-08-02

  The invention provides for novel cysteine protease inhibitors and compositions comprising novel cysteine protease derivatives. The invention further provides for methods for treatment of neurodegenerative diseases comprising administration novel cysteine protease inhibitors or compositions comprising novel cysteine protease inhibitors. In some embodiments, the cysteine protease inhibitors are calpain inhibitors.

  该发明提供了新型半胱氨酸蛋白酶抑制剂和包含新型半胱氨酸蛋白酶衍生物的组合物。该发明还提供了用于治疗神经退行性疾病的方法，包括给予新型半胱氨酸蛋白酶抑制剂或包含新型半胱氨酸蛋白酶抑制剂的组合物。在某些实施例中，这些半胱氨酸蛋白酶抑制剂是卡尔宁抑制剂。
• First Asymmetric Total Synthesis of Synerazol, an Antifungal Antibiotic, and Determination of Its Absolute Stereochemistry
  作者：Yujiro Hayashi、Mitsuru Shoji、Takasuke Mukaiyama、Hiroaki Gotoh、Shinpei Yamaguchi、Munetaka Nakata、Hideaki Kakeya、Hiroyuki Osada

  DOI：10.1021/jo050664x

  日期：2005.7.1

  first asymmetric total synthesis of synerazol, an antifungal antibiotic, has been accomplished, allowing determination of its absolute stereochemistry. A more practical second generation route was also established. The key steps are racemization-free deprotection of a TIPS group and introduction of a methyl ether by DMD oxidation of the benzylidene moiety in a substrate having a small protecting group

  通过合成两种可能的非对映异构体，已经完成了抗真菌抗菌药合那唑的首次不对称全合成，从而可以确定其绝对立体化学。还建立了更实用的第二代路线。关键步骤是TIPS基团的无消旋脱保护和通过DMD氧化具有小的保护基团的底物中的亚苄基部分来引入甲基醚。
• Novel Cysteine Protease Inhibitors and Uses Thereof
  申请人：The Trustees of Columbia University in the city of New York

  公开号：US20150045393A1

  公开（公告）日：2015-02-12

  The invention provides for novel cysteine protease inhibitors and compositions comprising novel cysteine protease derivatives. The invention further provides for methods for treatment of neurodegenerative diseases comprising administration novel cysteine protease inhibitors or compositions comprising novel cysteine protease inhibitors. In some embodiments, the cysteine protease inhibitors are calpain inhibitors.

  该发明提供了新型半胱氨酸蛋白酶抑制剂和包含新型半胱氨酸蛋白酶衍生物的组合物。该发明还提供了治疗神经退行性疾病的方法，包括给予新型半胱氨酸蛋白酶抑制剂或包含新型半胱氨酸蛋白酶抑制剂的组合物。在某些实施例中，半胱氨酸蛋白酶抑制剂为钙蛋白酶抑制剂。
• Design, Synthesis, and Optimization of Novel Epoxide Incorporating Peptidomimetics as Selective Calpain Inhibitors
  作者：Isaac T. Schiefer、Subhasish Tapadar、Vladislav Litosh、Marton Siklos、Rob Scism、Gihani T. Wijewickrama、Esala P. Chandrasena、Vaishali Sinha、Ehsan Tavassoli、Michael Brunsteiner、Mauro Fa’、Ottavio Arancio、Pavel Petukhov、Gregory R. J. Thatcher

  DOI：10.1021/jm4006719

  日期：2013.8.8

  Hyperactivation of the calcium-dependent cysteine protease calpain 1 (Call) is implicated as a primary or secondary pathological event in a wide range of illnesses and in neurodegenerative states, including Alzheimer's disease (AD). E-64 is an epoxide-containing natural product identified as a potent nonselective, calpain inhibitor, with demonstrated efficacy in animal models of AD. By use of E-64 as a lead, three successive generations of calpain inhibitors were developed using computationally assisted design to increase selectivity for Call. First generation analogues were potent inhibitors, effecting covalent modification of recombinant Call catalytic domain (Call(cat)), demonstrated using LC-MS/MS. Refinement yielded second generation inhibitors with improved selectivity. Further library expansion and ligand refinement gave three Call inhibitors, one of which was designed as an activity-based protein profiling probe. These were determined to be irreversible and selective inhibitors by kinetics studies comparing full length Call with the genera l cysteine protease papain.