N-tert-butoxycarbonyl[(1S,2S)-2-(aminomethyl)cyclopropyl]methanol | 1262755-28-1

• 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: N-tert-butoxycarbonyl[(1S,2S)-2-(aminomethyl)cyclopropyl]methanol
• 英文别名: Tert-butyl (((1S,2S)-2-(hydroxymethyl)cyclopropyl)methyl)carbamate；tert-butyl N-[[(1S,2S)-2-(hydroxymethyl)cyclopropyl]methyl]carbamate
• CAS: 1262755-28-1
• 化学式: C₁₀H₁₉NO₃
• 分子量: 201.266
• InChiKey: KXNPTSIIVCAMOC-HTQZYQBOSA-N

物化性质

• 沸点：
  317.0±15.0 °C(Predicted)
• 密度：
  1.071±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  14
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-tert-butoxycarbonyl[(1S,2S)-2-(aminomethyl)cyclopropyl]methanol 在 盐酸 、 戴斯-马丁氧化剂 作用下， 以 二氯甲烷 、 水 、 乙酸乙酯 为溶剂， 反应 15.17h， 生成 (1R,2R)-1-aminomethyl-2-carboxycyclopropane hydrochloride
  参考文献：
  名称：

  Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports

  摘要：

  A series of cyclopropane-based conformationally restricted gamma-aminobutyric acid (GABA) analogs with stereochemical diversity, that is, the trans- and cis-2,3-methano analogs Ia and Ib and their enantiomers ent-Ia and ent-Ib, and also the trans- and cis-3,4-methano analogs IIa and IIb and their enantiomers ent-IIa and ent-Iib, were synthesized from the chiral cyclopropane units Type-a and Type-b that we developed. These analogs were systematically evaluated with four GABA transporter (GAT) subtypes. The trans-3,4-methano analog IIa had inhibitory effects on GAT3 (IC50 = 23.9 mu M) and betaine-GABA transporter1 (5.48 mu M), indicating its potential as an effective lead compound for the development of potent GAT inhibitors due to its hydrophilic and low molecular weight properties and excellent ligand efficiency. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.063
• 作为产物：
  描述：

  trans-4-trityloxy-2,3-methano-1-butanol 在 四溴化碳 、 palladium 10% on activated carbon 、 水 、 氢气 、 溶剂黄146 、 三苯基膦 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、101.33 kPa 条件下， 反应 48.67h， 生成 N-tert-butoxycarbonyl[(1S,2S)-2-(aminomethyl)cyclopropyl]methanol
  参考文献：
  名称：

  Cyclopropane-based conformational restriction of GABA by a stereochemical diversity-oriented strategy: Identification of an efficient lead for potent inhibitors of GABA transports

  摘要：

  A series of cyclopropane-based conformationally restricted gamma-aminobutyric acid (GABA) analogs with stereochemical diversity, that is, the trans- and cis-2,3-methano analogs Ia and Ib and their enantiomers ent-Ia and ent-Ib, and also the trans- and cis-3,4-methano analogs IIa and IIb and their enantiomers ent-IIa and ent-Iib, were synthesized from the chiral cyclopropane units Type-a and Type-b that we developed. These analogs were systematically evaluated with four GABA transporter (GAT) subtypes. The trans-3,4-methano analog IIa had inhibitory effects on GAT3 (IC50 = 23.9 mu M) and betaine-GABA transporter1 (5.48 mu M), indicating its potential as an effective lead compound for the development of potent GAT inhibitors due to its hydrophilic and low molecular weight properties and excellent ligand efficiency. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2013.06.063

文献信息

• An Expedient Asymmetric Synthesis of N-Protected (S,S)-2-Aminomethyl-1-cyclopropanecarboxylic Acid
  作者：David Aitken、Steven Bull、Iwan Davies、Ludovic Drouin、Jean Ollivier、Jennifer Peed

  DOI：10.1055/s-0030-1258814

  日期：2010.11

  An enantioselective synthesis of a N-Boc-protected trans-cyclopropane γ-amino acid is reported. The key chiral aldehyde intermediate is prepared in enantiomerically pure form using a three-step aldol-cyclopropanation-retro-aldol protocol.

  报道了一种手性选择性的合成N-Boc保护的反式环丙烷γ-氨基酸的方法。关键的手性醛中间体采用三步醛醇-环丙烷化-逆醛醇的方法制备，得到对映体纯度高的形式。
• Discovery and Structure-Based Design of Macrocyclic Peptides Targeting STUB1
  作者：Simon Ng、Alexander C. Brueckner、Soheila Bahmanjah、Qiaolin Deng、Jennifer M. Johnston、Lan Ge、Ruchia Duggal、Bahanu Habulihaz、Benjamin Barlock、Sookhee Ha、Ahmad Sadruddin、Constance Yeo、Corey Strickland、Andrea Peier、Brian Henry、Edward C. Sherer、Anthony W. Partridge

  DOI：10.1021/acs.jmedchem.2c00406

  日期：2022.7.28

  are lacking. Identifying a tool compound will be a step toward validating the target in a broader therapeutic sense. Herein, screening more than a billion macrocyclic peptides resulted in STUB1 binders, which were further optimized by a structure-enabled in silico design. The strategy to replace the macrocyclic peptides’ hydrophilic and solvent-exposed region with a hydrophobic scaffold improved cellular

  最近的证据表明，删除 STUB1（干扰素-γ 传感的关键负调节因子）可能会清除恶性细胞。然而，目前的研究主要依赖于遗传方法，因为缺乏 STUB1 的药理学抑制剂。识别工具化合物将是在更广泛的治疗意义上验证靶标的一步。在此，筛选了超过 10 亿个大环肽，产生了 STUB1 结合物，并通过计算机设计中的结构进一步优化。用疏水性支架取代大环肽的亲水性和溶剂暴露区域的策略改善了细胞通透性，同时保持了结合构象。用四唑生物等排体进一步取代限制通透性的末端天冬氨酸，在一定程度上保留了结合，同时提高了通透性，这表明了一条前进的道路。尽管对于细胞研究来说不是最佳的，但当前的先导化合物为进一步开发 STUB1 的选择性工具化合物以实现目标验证提供了有价值的模板。