(αS,3R,4S)-α-amino-(4-hydroxypyrrolidin-3-yl)acetic acid | 1527565-12-3

• 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: (αS,3R,4S)-α-amino-(4-hydroxypyrrolidin-3-yl)acetic acid
• 英文别名: (2S)-2-azaniumyl-2-[(3R,4S)-4-hydroxypyrrolidin-3-yl]acetate
• CAS: 1527565-12-3
• 化学式: C₆H₁₂N₂O₃
• 分子量: 160.173
• InChiKey: CNJVSSXLDMADHN-LMVFSUKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -3.2
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  100
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  (1S,2S,2'S,3'R,3'aS,5R)-2','3-bis(chloromethyl)-2-isopropyl-5,5'-dimethyl-3',3'a-dihydro-2'H-spiro[cyclohexane-1,6'-imidazo[1,5-b]-isoxazol]-4'(5'H)-one 在 盐酸 、 sodium azide 、 10 wt% Pd(OH)2 on carbon 、 氢气 、 三苯基膦 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 水 、 溶剂黄146 、 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 20.0~80.0 ℃ 、101.33 kPa 条件下， 反应 380.0h， 生成 (αS,3R,4S)-α-amino-(4-hydroxypyrrolidin-3-yl)acetic acid
  参考文献：
  名称：

  对映体纯 3-Glycinyl-4-羟基吡咯烷和 3-取代 4-羟基脯氨酸的环加成-环化联合方法

  摘要：

  (E)-或(Z)-1,4-二氯-2-丁烯和薄荷酮衍生的硝酮作为甘氨酸等价物之间的环加成反应提供基于二氯化异恶唑烷的环加合物。这些加合物的立体化学由起始烯烃和硝酮的构型控制。氨基是通过异恶唑烷 N-O 键的还原裂解或通过叠氮化和随后的还原产生的，这在两条路线中引发了环化反应，通过氯化物置换进行。这种方法提供了前所未有的 3-取代 4-羟基脯氨酸衍生物和 (αS,3R,4S)-3-glycinyl-4-hydroxypyrrolidine。报道的产品的两种对映体都可以通过使用一种或另一种硝酮对映体来制备。

  DOI：

  10.1002/ejoc.201402215

文献信息

• NOVEL PYRROLIDINE DERIVATIVES
  申请人：UNIVERSITE CLAUDE BERNARD LYON I

  公开号：US20150175537A1

  公开（公告）日：2015-06-25

  The present invention relates to novel pyrrolidine derivatives of formula (I): wherein R 1 , R 2 , R 3 , R 4 , R 5 and X are as defined in claim 1 , optionally in a zwitterionic form, in the form of a pure optical isomer, or in the form of a mixture of optical isomers in any proportions, or in a form enriched with an optical isomer, as well as their pharmaceutically acceptable salts, solvates or hydrates, and pharmaceutical compositions containing such compounds. These compounds are notably useful for treating, in particular in human beings, epilepsy, ischemia, neurodegenerative diseases such as Parkinson's disease or Huntington's chorea, multiple sclerosis, Devic's disease, Alzheimer's disease, psychiatric diseases such as schizophrenia, depression, addiction, allodynia and hyperalgia.

  本发明涉及公式(I)的新型吡咯烷衍生物：其中R1、R2、R3、R4、R5和X如权利要求书中定义的，可选地为带电离形式，以纯的光学异构体形式、或以任何比例的光学异构体混合物形式、或以富含光学异构体的形式存在，以及它们的药学上可接受的盐、溶剂合物或水合物，以及含有这些化合物的药物组合物。这些化合物特别适用于治疗，特别是在人类中，癫痫、缺血、帕金森病或亨廷顿舞蹈病等神经退行性疾病、多发性硬化症、德维克病、阿尔茨海默病、精神疾病如精神分裂症、抑郁症、成瘾、痛觉过敏和疼痛过敏。
• Novel routes to either racemic or enantiopure α-amino-(4-hydroxy-pyrrolidin-3-yl)acetic acid derivatives and biological evaluation of a new promising pharmacological scaffold
  作者：Samy Cecioni、Kaïss Aouadi、Julie Guiard、Sandrine Parrot、Nathalie Strazielle、Sandrine Blondel、Jean-François Ghersi-Egea、Christian Chapelle、Luc Denoroy、Jean-Pierre Praly

  DOI：10.1016/j.ejmech.2015.05.017

  日期：2015.6

  Cycloaddition between (+) or (-)-menthone-derived nitrones and N-benzyl-3-pyrroline afforded enantiopure spiro-fused heterocycles. The reaction occurred enantio- and diastereo-selectively on the less hindered side of the nitrone, the 3-pyrroline N-benzyl group being oriented outwards, thus controlling the configurations of three simultaneously created chiral centers. From either (+) or (-)-menthone, both enantiomeric cycloadducts were synthesized in excellent yield. Removing the chiral auxiliary and the N-benzyl group delivered a series of enantiopure 4-hydroxy-3-glycinyl-pyrrolidine derivatives in 3-5 steps and 36 to 81 overall yields. Using two other achiral nitrones, shorter routes to racemic analogues were developed. Two of the synthesized compounds markedly lowered extracellular glutamate level and modestly interacted with cannabinoid type-1 receptors. As these two neuroactive compounds were devoid of in vitro toxicity and did not cross the blood brain interface, they might represent potential pharmacological agents to target peripheral organs. (C) 2015 Elsevier Masson SAS. All rights reserved.
• US9199931B2
  申请人：——

  公开号：US9199931B2

  公开（公告）日：2015-12-01