S-2-羟基戊二酸 | 13095-48-2

• 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
• 中文名称: S-2-羟基戊二酸
• 中文别名: (2S)-2-羟基戊二酸
• 英文名称: L-hydroxyglutaric acid
• 英文别名: L-2-hydroxyglutarate；L-2-hydroxyglutaric acid；(S)-2-hydroxyglutaric acid；(S)-2-hydroxyglutarate；(2S)-2-hydroxypentanedioic acid
• CAS: 13095-48-2
• 化学式: C₅H₈O₅
• 分子量: 148.116
• InChiKey: HWXBTNAVRSUOJR-VKHMYHEASA-N

物化性质

• 沸点：
  394.2±27.0 °C(Predicted)
• 密度：
  1.508±0.06 g/cm3(Predicted)
• 溶解度：
  DMF：30mg/mL； DMSO：30mg/mL；乙醇：30mg/mL； PBS（pH 7.2）：10 mg/mL
• 物理描述：
  Solid
• 碰撞截面：
  118.99 Ų [M-H]- [CCS Type: DT, Method: single field calibrated with Agilent tune mix (Agilent)]

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  10
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  94.8
• 氢给体数：
  3
• 氢受体数：
  5

ADMET

毒理性

• 毒性总结

2-羟基戊二酸是一种癌代谢物。它是多种依赖于α-酮戊二酸的二氧合酶的竞争性抑制剂，包括组蛋白去甲基化酶和5-甲基胞嘧啶（5mC）羟基化酶的TET家族。因此，2-羟基戊二酸高水平会导致全基因组组蛋白和DNA甲基化改变，进而导致最终引发癌症的突变。L-2-羟基戊二酸通过激活N-甲基-D-天冬氨酸受体介导其神经毒性。L-2-羟基戊二酸的 结构与兴奋性氨基酸谷氨酸相似，并通过谷氨酸、NMDA或线粒体毒素（A15198）的已知机制刺激神经退行。

2-hydroxyglutarate is an oncometabolite. It is a competitive inhibitor of multiple α-ketoglutarate-dependent dioxygenases, including histone demethylases and the TET family of 5-methlycytosine (5mC) hydroxylases. As a result, high levels of 2-hydroxyglutarate lead to genome-wide histone and DNA methylation alterations, which in turn lead to mutations that ultimately cause cancer. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. L-2-hydroxyglutarate is structurally similar to the excitatory amino acid glutamate and stimulates neurodegeneration by mechanisms well-known for glutamate, NMDA or mitochondrial toxins (A15198).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列入国际癌症研究机构(IARC)名录。已涉及致癌作用（A15091, A15090）。

Not listed by IARC. Has been implicated in oncogenesis (A15091, A15090).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

慢性高水平的L-2-羟基戊酸与称为2-羟基戊酸尿症的遗传代谢错误有关。L-2-羟基戊酸盐具有神经毒性。L-2-羟基戊酸盐通过激活N-甲基-D-天门冬氨酸受体来发挥其神经毒性。L-2-羟基戊酸尿症的症状包括肌张力低下、震颤和癫痫，逐渐发展为海绵状白质脑病、肌肉舞蹈病、智力迟钝和运动技能退化。

Chronically high levels of L-2-hydroxyglutaric acid are associated with the inborn error of metabolism called: 2-Hydroxyglutaric Aciduria. L-2-hydroxyglutarate is neurotoxic. L-2-hydroxyglutarate mediates its neurotoxicity through activation of N-methyl-D-aspartate receptors. Symptoms of L-2-Hydroxyglutaric Aciduria include hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 暴露途径

内生的，注入

Endogenous, Injection

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 症状

长期暴露于高水平L-2-羟基戊酸会导致肌张力减退、震颤和癫痫，进而发展为海绵状白质脑病、肌肉舞蹈病、智力障碍和运动技能退化。

Chronic exposure of high levels of L-2-hydroxyglutarate leads to hypotonia, tremors, and epilepsy declining into spongiform leukoencephalopathy, muscular choreodystonia, mental retardation, and psychomotor regression.

来源:Toxin and Toxin Target Database (T3DB)

安全信息

• 海关编码：
  2918199090
• 储存条件：
  -20°C下应密封并置于干燥处保存。

制备方法与用途

生物活性

L-2-羟基戊二酸 ((S)-2-羟基戊二酸) 是一种表观遗传修饰因子，可用于肾癌研究。它能够抑制组蛋白去甲基化酶（histone demethylases），从而促进组蛋白甲基化。

靶点

Human 内源性代谢物

体外研究

L-2-羟基戊二酸对2-酮戊二酸依赖的双加氧酶（2OGDs）具有很强的抑制作用，包括Ten Eleven 转位 (TET) 酶。

反应信息

• 作为反应物：
  描述：

  S-2-羟基戊二酸 在 对甲苯磺酸 作用下， 以 苯 为溶剂， 140.0~150.0 ℃ 、1.33 Pa 条件下， 生成 (2S)-tetrahydro-5-oxo-2-furancarboxylic acid ethyl ester
  参考文献：
  名称：

  Pirillo; Leggeri; Traverso, Farmaco, Edizione Scientifica, 1984, vol. 39, # 5, p. 473 - 476

  摘要：

  DOI：
• 作为产物：
  描述：

  alpha-酮戊二酸 在 Mucor rouxii yeast-like cells 、 Novozym 435 lipase B from Candida antarctica 作用下， 以 正己烷 、 水 为溶剂， 反应 40.0h， 生成 S-2-羟基戊二酸
  参考文献：
  名称：

  Combination strategy using pure enzymes and whole cells as biocatalysts for the preparation of 2-hydroxyesters and lactones from 2-oxoglutaric acid

  摘要：

  An innovative combination strategy that uses pure enzymes and whole microbial cells in the same process was used to prepare enantionterically pure 3-carboxyalkyl-gamma-butyrolactones and several alkyl esters of 2-hydroxyglutarates from 2-oxoglutaric acid. The method involves two consecutive biocatalytic steps. The first step, which converts the 2-oxoglutaric acid into the corresponding dialkyl esters, was catalyzed by a lipase. Then in the second step, by microbial reduction of the dialkyl-2-oxoglutarates, it is possible to obtain 3-carboxyalkyl-gamma-butyrolactones or 2-hydroxyesters depending on the length of the chain in the alkyl moiety of the esters and on the fresh or lyophilized status of the cells. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2004.10.013

文献信息

• Synthesis of C1C11 fragment of annonacin: a polyketide acetogenin of Annonaceae
  作者：Bruno Figadère、Xavier Franck、André Cavé

  DOI：10.1016/0040-4039(95)00083-o

  日期：1995.3

  tri-isopropylsilyloxy-4-tert-butyldimethylsilyloxy-10-tert-amyloxy-11-undecanoate 1 has been synthesized from L-glutamic acid. This compound is a key intermediate in the total synthesis of annonacin, an acetogenin of Annonaceae.

  （4R，10S） -甲基三isopropylsilyloxy -4-叔丁基二甲硅烷氧基-10-叔戊氧基-11-十一酸盐1已经从L-谷氨酸合成。该化合物是番荔枝科的产乙酸素—番荔枝素的全部合成中的关键中间体。
• ADMINISTRATION OF LORCASERIN TO INDVIDUALS WITH RENAL IMPAIRMENT
  申请人：Arena Pharmaceuticals, Inc.

  公开号：EP2939677A1

  公开（公告）日：2015-11-04

  The present disclosure relates to methods for weight management in an individual in need thereof by determining the level of renal sufficiency of the individual and prescribing or administering a therapeutically effective amount of (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof to the individual, provided that the individual has a level of renal sufficiency selected from the group consisting of: no renal impairment, mild renal impairment, and moderate renal impairment. In addition, the disclosure relates to a method for selecting an individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof from a plurality of individuals in need of weight management by determining the level of renal sufficiency of the individual and selecting the individual for treatment with (R)-8-chloro-1-methyl-2,3,4,5-tetrahydro-1H-3-ben-zazepine or a pharmaceutically acceptable salt, solvate or hydrate thereof if the individual has a level of renal sufficiency selected from the group consisting of: no renal impairment, mild renal impairment, and moderate renal impairment.

  本公开涉及一种通过确定个体的肾功能充分性水平并向该个体开具或给予(R)-8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并噁唑啉或其药学上可接受的盐、溶剂或水合物的治疗有效量来进行个体的体重管理的方法，前提是该个体的肾功能充分性水平选自以下组合：无肾功能障碍、轻度肾功能障碍和中度肾功能障碍。此外，本公开涉及一种通过确定个体的肾功能充分性水平并从需要体重管理的众多个体中选择个体进行(R)-8-氯-1-甲基-2,3,4,5-四氢-1H-3-苯并噁唑啉或其药学上可接受的盐、溶剂或水合物治疗的方法，如果该个体的肾功能充分性水平选自以下组合：无肾功能障碍、轻度肾功能障碍和中度肾功能障碍。
• Synthesis of Two Epimers of Pseudopaline
  作者：Gregorio Cullia、Roberto Fanelli、Romé Voulhoux、Pascal Arnoux、Florine Cavelier

  DOI：10.1002/ejoc.202000278

  日期：2020.7.15

  development during infections, providing a route for the acquirement of essential micronutrients (Zn2+ and Mn2+) in metal scarce environments. Herein, a straightforward synthetic approach for the synthesis of two epimers of pseudopaline and the attribution of their absolute configurations is presented.

  Pseudopaline是最近在铜绿假单胞菌中发现的一种鸦片金属螯合剂。这种金属团簇在感染过程中的细菌发育中起着重要作用，为在金属匮乏的环境中获取必需的微量营养素（Zn 2+和Mn 2+）提供了一条途径。在这里，提出了一种简单的合成方法，用于合成假胭脂红的两个差向异构体及其绝对构型的归属。
• Charged chiral derivatization for enantioselective imaging of <scp>d-,l</scp>-2-hydroxyglutaric acid using ion mobility spectrometry/mass spectrometry
  作者：Eiji Sugiyama、Yuki Nishiya、Kenji Yamashita、Ryo Hirokawa、Yoshiteru Iinuma、Takashi Nirasawa、Hajime Mizuno、Yoshitaka Hamashima、Kenichiro Todoroki

  DOI：10.1039/d3cc01963b

  日期：——

  synthesized charged chiral tag-enabled enantioselective imaging of D-,L-2-hydroxyglutaric acid, which are independently associated with the regulation of DNA methylation. The tag-conjugated diastereomers were ionized efficiently through MALDI, separated by ion mobility spectrometry, and further separated from other molecules in mass spectrometry. On-tissue chiral derivatization using the tag facilitated

  新合成的带电手性标签可对D -, L -2-羟基戊二酸进行对映选择性成像，其与 DNA 甲基化的调节独立相关。标签缀合的非对映异构体通过 MALDI 有效电离，通过离子迁移谱分离，并在质谱中进一步与其他分子分离。使用该标签进行的组织手性衍生化有助于观察小鼠睾丸中两种异构体的不同分布。
• Synergetic Multichiral Covalent Organic Framework for Enantioselective Recognition and Separation
  作者：Yanlong Chen、Simin Huang、Ling Xia、Yuling Hu、Gongke Li

  DOI：10.1021/acs.analchem.3c05227

  日期：2024.1.23

  recognition and separation of various enantiomers. As expected, the GSH-MCD COF can be used as chiral stationary phases for the separation of various enantiomers, including aromatic alcohols, aromatic acids, amides, amino acids, and organic acids, with performance and versatility even superior to some widely used commercial chiral chromatographic columns. Furthermore, the synthesized GSH-MCD COF shows high

  在对映体识别和分离中，迫切需要一种具有普遍适用性的高度对映选择性方法，但很难实现，特别是在手性分子的情况下。为了解决对映选择性和通用性之间的权衡，设计并合成了一种具有多孔性和丰富的手性表面的谷胱甘肽（GSH）和甲基化环糊精（MCD）功能化的共价有机框架（GSH-MCD COF），用于识别和分离各种对映体。正如预期的那样，GSH-MCD COF 可用作分离各种对映体的手性固定相，包括芳香醇、芳香酸、酰胺、氨基酸和有机酸，其性能和多功能性甚至优于一些广泛使用的商业手性固定相色谱柱。此外，合成的 GSH-MCD COF 在与拉曼光谱耦合时表现出高对映选择性，可快速识别和鉴定对映体和手性代谢物。分子模拟表明，COF 为环糊精和肽提供了一个有限的微环境，决定了分离和识别能力。这项工作提供了一种合成协同多手性COF并实现复杂样品中对映体分离和识别的策略。