methyl (1S,2S)-2-aminocyclopentanecarboxylate hydrochloride | 1024618-18-5

• 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: methyl (1S,2S)-2-aminocyclopentanecarboxylate hydrochloride
• 英文别名: methyl (1S,2S)-2-aminocyclopentane-1-carboxylate hydrochloride；Methyl trans-2-aminocyclopentanecarboxylate;hydrochloride；methyl (1S,2S)-2-aminocyclopentane-1-carboxylate;hydrochloride
• CAS: 1024618-18-5
• 化学式: C₇H₁₃NO₂*ClH
• 分子量: 179.647
• InChiKey: KXQFCNYQRWIKML-GEMLJDPKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.71
• 重原子数：
  11
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  52.3
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl (1S,2S)-2-aminocyclopentanecarboxylate hydrochloride 在 锂硼氢 、 sodium hydride 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 5.17h， 生成 N-[(1S,2S)-2-[(5-fluoro-2-pyridyl)oxymethyl]cyclopentyl]-2-methoxy-6-(triazol-2-yl)benzamide
  参考文献：
  名称：

  [EN] OREXIN 1 RECEPTOR ANTAGONISTS
  [FR] ANTAGONISTES DES RÉCEPTEURS DE L'OREXINE 1

  摘要：

  本公开涉及公式（I）的新化合物及其盐，其中W；X；Y；Z；R1；R2；R3和R4在此处定义，并其在治疗、预防、改善、控制或减少与促进素受体相关的神经系统或精神障碍的风险中的用途。

  公开号：

  WO2020120994A1
• 作为产物：
  描述：

  -(R)-(+)-α-methylbenzylamine 在 盐酸 、 氯化亚砜 、 三氟乙酸 作用下， 反应 14.0h， 生成 methyl (1S,2S)-2-aminocyclopentanecarboxylate hydrochloride
  参考文献：
  名称：

  Probing a molecular model of taste utilizing peptidomimetic stereoisomers of 2-aminocyclopentanecarboxylic acid methyl ester

  摘要：

  On the basis of the preferred conformations of L-aspartyl dipeptide derivatives containing alpha-amino acids at the second position and their retro-inverso analogues deduced by a combination of X-ray crystallography, H-1 NMR spectroscopy, and molecular mechanics calculations, we have proposed a model describing the molecular array required for the sweet taste. The conformation of a sweet molecule is described as possessing an "L shape", with the AH (proton donor) and B (proton acceptor) zwitterionic ring of the aspartyl moiety forming the stem, and the hydrophobic group X forming the base of the "L". Planarity of the molecule in the x and y dimensions is critical for sweet taste. Substantial deviation from this plane into negative z dimension is correlated with bitter taste while other deviations lead to tasteless molecules. To examine the model, the preferred conformations for a series of L-aspartyl dipeptides containing a 2-aminocyclopentanecarboxylic acid (2-Ac5c) residue at the second position were calculated using molecular mechanics. The peptidomimetic 2-Ac5c residue is a beta-amino acid with two chiral centers, resulting in four isomers [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c, cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c]. Two stereoisomers, L-aspartyl-trans-(1R,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1R,2R)-2-Ac5c-OMe] and L-aspartyl-cis-(1S,2R)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1S,2R)-2-Ac5c-OMe], prefer the L-shape conformations and are thus predicted to be sweet. For L-aspartyl-trans-(1S,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-trans-(1S,2S)-2-Ac5c-OMe], the methyl ester group projects behind the stem of the L shape, producing a large negative z component and is predicted to exhibit a bitter taste. The calculations predict that L-aspartyl-cis-(1R,2S)-2-aminocyclopentanecarboxylic acid methyl ester [Asp-cis-(1R,2S)-2-Ac5c-OMe] will be tasteless. In this investigation, in addition to the calculations, we report the synthesis and experimental conformational analysis of the four stereoisomers of Asp-2-Ac5c-OMe. The absolute configurations of the 2-Ac5c residues were assigned by X-ray diffraction studies and by correlating optical rotation and enantiomeric excess values. These studies fully confirm our configurational assignments of the stereoisomers of Asp-2-Ac5c-OMe. Thus, the structure-taste relationships observed for the new class of L-aspartyl taste ligands containing the 2-Ac5c beta-amino acid methyl esters in the second position agree with and strengthen our model for the sweet and bitter taste responses.

  DOI：

  10.1021/jo00023a033

文献信息

• [EN] OREXIN 1 RECEPTOR ANTAGONISTS<br/>[FR] ANTAGONISTES DU RÉCEPTEUR DE L'OREXINE 1
  申请人：HEPTARES THERAPEUTICS LTD

  公开号：WO2020157474A1

  公开（公告）日：2020-08-06

  The disclosures herein relate to novel compounds of formula (1) and salts thereof, wherein V; W; X; Y; Z; R1; R2; R3; R4 and R5 are defined herein, and their use in treating, preventing, ameliorating, controlling or reducing the risk of neurological or psychiatric disorders associated with orexin receptors.

  本公开涉及公式（1）的新化合物及其盐，其中V；W；X；Y；Z；R1；R2；R3；R4和R5在此处定义，并其在治疗、预防、缓解、控制或降低与促觉素受体相关的神经或精神障碍的风险中的用途。
• The Bip Method, Based on the Induced Circular Dichroism of a Flexible Biphenyl Probe in Terminally Protected -Bip-Xaa*- Dipeptides, for Assignment of the Absolute Configuration of β-Amino Acids
  作者：Laurence Dutot、Karen Wright、Anne Gaucher、Michel Wakselman、Jean-Paul Mazaleyrat、Marta De Zotti、Cristina Peggion、Fernando Formaggio、Claudio Toniolo

  DOI：10.1021/ja800059d

  日期：2008.5.1

  An induced axial chirality of the biphenyl core of the Bip (2',1':1,2;1'',2'':3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid) residue in the terminally protected dipeptides Boc-Bip-beta-Xaa*-OMe (beta-Xaa* = L-beta(3)-HAla, L-beta(3)-HVal, L-beta(3)-HLeu, L-beta(3)-HPro, trans-(1S,2S)-ACHC, trans-(1R,2R)-ACHC, trans-(1S,2S)-ACPC, trans-(1R,2R)-ACPC) resulted in an induced circular dichroism

  Bip 联苯核的诱导轴向手性 (2',1':1,2;1'',2'':3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carb acid ) 末端保护的二肽 Boc-Bip-beta-Xaa*-OMe (beta-Xaa* = L-beta(3)-HAla, L-beta(3)-HVal, L-beta(3)-HLeu, L-beta(3)-HPro, trans-(1S,2S)-ACHC, trans-(1R,2R)-ACHC, trans-(1S,2S)-ACPC, trans-(1R,2R)-ACPC)在诱导圆二色性中，揭示了 Bip 方法在可靠和快速分配手性 β-氨基酸的绝对构型方面的有用性。值得注意的是，Bip 方法还应用于独特的自旋标记、环状、β-氨基酸顺式/反式-β-TOAC 和反式-POAC。特别是，这项研究允许分配后一种化合物的对映异构体的未知绝对构型。
• Synthesis, resolution and assignment of absolute configuration of trans 3-amino-1-oxyl-2,2,5,5-tetramethylpyrrolidine-4-carboxylic acid (POAC), a cyclic, spin-labelled β-amino acid
  作者：Karen Wright、Laurence Dutot、Michel Wakselman、Jean-Paul Mazaleyrat、Marco Crisma、Fernando Formaggio、Claudio Toniolo

  DOI：10.1016/j.tet.2008.02.058

  日期：2008.5

  absolute configuration of the asymmetric C3, C4 carbons of POAC were assigned from the induced circular dichroism of a flexible biphenyl probe present in the terminally protected dipeptide derivatives Boc-Bip-(+)-POAC-OMe and Boc-Bip-(−)-POAC-OMe (Bip, 2′,1′:1,2;1″,2″:3,4-dibenzcyclohepta-1,3-diene-6-amino-6-carboxylic acid). This assignment was confirmed by X-ray diffraction analysis of the diastereomeric

  通过常规方法制备的外消旋反式3-（9-芴基甲氧基羰基氨基）-1-氧基-1,2,2,5,5-四甲基吡咯烷-4-羧酸（Fmoc-POAC-OH）经（a R）酯化后拆分-2,2'-二羟基-1,1'-联萘基。通过结晶/色谱法分离获得的非对映体单酯Fmoc-（±）-反式-POAC- O-（a R）-联萘酚，并通过对芳基酯官能进行皂化除去手性助剂，提供了两种对映体（+）-（ 3 R，4 R）-Fmoc-POAC-OH和（-）-（3 S，4 S）-Fmoc-POAC-OH。不对称C 3，C 4的绝对构型POAC的碳是由存在于末端保护的二肽衍生物Boc-Bip-（+）-POAC-OMe和Boc-Bip-（-）-POAC-OMe中的柔性联苯探针的诱导圆二色性分配的（Bip，2' ，1'：1,2; 1''，2''：3,4-dibenzcyclohepta-1,3-diene-6-amino-6-羧酸）。该分配
• Synthesis and Conformational Characterisation of Hexameric β-Peptide Foldamers by Using Double POAC Spin Labelling and cw-EPR
  作者：Karen Wright、Michel Wakselman、Jean-Paul Mazaleyrat、Lorenzo Franco、Antonio Toffoletti、Fernando Formaggio、Claudio Toniolo

  DOI：10.1002/chem.201000821

  日期：——

  5‐tetramethylpyrrolidine‐3‐carboxylic acid (POAC) residues combined with four (1S,2S)‐2‐aminocyclopentane‐1‐carboxylic acid (ACPC) residues, was synthesised by using solution methods and was fully characterised. The two POAC residues are separated in the sequences by different numbers of intervening ACPC residues. The conformational features of the doubly spin‐labelled β‐hexapeptides were examined in chloroform

  一组选定的末端保护的β-六肽，每个均包含两个基于氮氧化物的（3 R，4 R）-4-氨基-1-氧基-2,2,5,5-四甲基吡咯烷-3-羧酸（POAC）残基结合四个（1 S，2 S）-2-氨基环戊烷-1-羧酸（ACPC）残基，采用溶液法合成并进行了充分表征。两个POAC残基在序列中被不同数量的中间ACPC残基隔开。通过FTIR吸收和连续波电子顺磁共振波谱技术，在氯仿中检查了双自旋标记的β-六肽的构象特征。特别是双自由基交换偶合（J）在每个肽中的两个POAC残基之间明确表示绝大多数采用的二级结构是12螺旋。综上所述，这些结果支持以下观点：POAC是一种出色的β-氨基酸，可用于探索双标记β-肽中的这种螺旋构象。
• Versatile Post‐synthetic Modifications of Helical β‐Peptide Foldamers Derived from a Thioether‐Containing Cyclic β‐Amino Acid
  作者：Danim Lim、Wonchul Lee、Jungwoo Hong、Jintaek Gong、Jonghoon Choi、Jaewook Kim、Seolhee Lim、Sung Hyun Yoo、Yunho Lee、Hee‐Seung Lee

  DOI：10.1002/anie.202305196

  日期：2023.9.25

  We introduce a novel cyclic β‐amino acid, trans‐(3S,4R)‐4‐aminotetrahydrothiophene‐3‐carboxylic acid (ATTC), as a versatile building block for designing peptide foldamers with controlled secondary structures. We synthesized and characterized a series of β‐peptide hexamers containing ATTC using various techniques, including X‐ray crystallography, circular dichroism, and NMR spectroscopy. Our findings reveal that ATTC‐containing foldamers can adopt 12‐helical conformations similar to their isosteres and offer the possibility of fine‐tuning their properties via post‐synthetic modifications. In particular, chemoselective conjugation strategies demonstrate that ATTC provides unique post‐synthetic modification opportunities, which expand their potential applications across diverse research areas. Collectively, our study highlights the versatility and utility of ATTC as an alternative to previously reported cyclic β‐amino acid building blocks in both structural and functional aspects, paving the way for future research in the realm of peptide foldamers and beyond.

  摘要 我们介绍了一种新型环状β-氨基酸--反式-(3S,4R)-4-氨基四氢噻吩-3-羧酸（ATTC），它是设计具有可控二级结构的肽折叠体的多功能构建模块。我们利用 X 射线晶体学、圆二色光谱和核磁共振光谱等多种技术合成了一系列含有 ATTC 的 β 肽六聚体，并对其进行了表征。我们的研究结果表明，含有 ATTC 的折叠体可以采用与其同源物类似的 12 螺旋构象，并提供了通过合成后修饰微调其特性的可能性。特别是化学选择性共轭策略表明，ATTC 提供了独特的合成后修饰机会，从而拓展了它们在不同研究领域的潜在应用。总之，我们的研究强调了 ATTC 作为以前报道过的环状 β- 氨基酸构筑基块的替代品在结构和功能方面的多功能性和实用性，为肽折叠器领域及其他领域的未来研究铺平了道路。