(1S,2R)-methyl 2-(tert-butoxycarbonylamino)cyclopentanecarboxylate | 592503-70-3

• 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: (1S,2R)-methyl 2-(tert-butoxycarbonylamino)cyclopentanecarboxylate
• 英文别名: cis-(1S,2R)-2-tert-butoxycarbonylamino-cyclopentanecarboxylic acid ethyl ester；methyl (1R,2S)-2-[(2-methylpropan-2-yl)oxycarbonylamino]cyclopentane-1-carboxylate
• CAS: 592503-70-3
• 化学式: C₁₂H₂₁NO₄
• 分子量: 243.303
• InChiKey: LVSNFSRSQZFNPY-BDAKNGLRSA-N

物化性质

• 沸点：
  331.8±31.0 °C(Predicted)
• 密度：
  1.08±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  17
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1S,2R)-methyl 2-(tert-butoxycarbonylamino)cyclopentanecarboxylate 在 lithium aluminium tetrahydride 、 potassium tert-butylate 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 、 mineral oil 为溶剂， 反应 1.0h， 生成 (4aS,aR)-1-(5-phenylethynylpyridin-2-yl)hexahydrocyclopenta[d][1,3]oxazin-2-one
  参考文献：
  名称：

  [EN] ARYLETHYNYL DERIVATIVES
  [FR] DÉRIVÉS D'ARYLÉTHYNYLE

  摘要：

  本发明涉及公式（I）的乙炔衍生物，其中：•R是苯基、3-氟苯基、4-氟苯基或2,5-二氟苯基；•或以绝对构型为公式（I）所示的对映体纯形式的药学上可接受的酸加盐。现已惊奇地发现，公式I的化合物是代谢型谷氨酸受体亚型5（mGluR5）的变构调节剂，对治疗精神分裂症、认知障碍、脆性X综合症或自闭症有用，并且与先前技术的化合物相比，具有优越的生化、物理化学和药动学性质。

  公开号：

  WO2014056710A1
• 作为产物：
  描述：

  5-己烯醛 在 palladium dihydroxide ruthenium(IV) oxide 、 sodium periodate 、 9-borabicyclo[3.3.1]nonane dimer 、 偶氮二异丁腈 、 camphor-10-sulfonic acid 、 氢气 、 sodium acetate 、 三乙胺 、 间氯过氧苯甲酸 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 正己烷 、 二氯甲烷 、 水 、 丙酮 、 苯 为溶剂， 反应 70.5h， 生成 (1S,2R)-methyl 2-(tert-butoxycarbonylamino)cyclopentanecarboxylate
  参考文献：
  名称：

  杂环合成中的自由基环化。第13部分：硫烷基自由基加成—与烯烃连接的肟醚和的环化反应，以合成环状β-氨基酸

  摘要：

  硫醚基自由基加成－肟醚和与烯烃连接的的环化反应以及随后苯硫烷基甲基到羧基的转化提供了一种构造环状β-氨基酸的新方法。在AIBN存在下用苯硫酚处理后，使肟醚和平稳地进行硫烷基自由基加成-环化反应，得到2-（苯基硫烷基甲基）环烷基胺。该方法已成功应用于2-氨基环戊烷羧酸和4-氨基-3-吡咯烷羧酸的实际合成。

  DOI：

  10.1016/s0040-4020(02)00412-x

文献信息

• ORNITHINE DERIVATIVE
  申请人：Astellas Pharma Inc.

  公开号：EP2141147A1

  公开（公告）日：2010-01-06

  Provided is a compound which is useful as a therapeutic agent for chronic renal insufficiency and a therapeutic agent for diabetic nephropathy. The present inventors have made extensive studies on an ornithine derivative having an antagonistic action against an EP4 receptor, and as a result, they have found that by introducing cycloalkanediyl at a C terminal of the ornithine part of the compound of the present invention, the physicochemical properties such as solubility, and the like can be improved, thereby giving further preferred properties as a pharmaceutical. Therefore, they have completed the present invention. The compound of the present invention exhibits a good antagonistic action against an EP4 receptor, and thus, it is useful as a therapeutic agent for chronic renal insufficiency and diabetic nephropathy.

  提供了一种化合物，可用作慢性肾功能不全的治疗剂和糖尿病肾病的治疗剂。目前的发明人对具有对EP4受体拮抗作用的鸟氨酸衍生物进行了广泛研究，结果发现通过在目前发明的化合物的鸟氨酸部分的C末端引入环烷基，可以改善物理化学性质，如溶解性等，从而赋予其作为药物的更优越性质。因此，他们完成了这项发明。目前发明的化合物对EP4受体表现出良好的拮抗作用，因此，它可用作慢性肾功能不全和糖尿病肾病的治疗剂。
• Probing a molecular model of taste utilizing peptidomimetic stereoisomers of 2-aminocyclopentanecarboxylic acid methyl ester
  作者：Toshimasa Yamazaki、Yun Fei Zhu、Albert Probstl、Raj K. Chadha、Murray Goodman

  DOI：10.1021/jo00023a033

  日期：1991.11

  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.
• US8030489B2
  申请人：——

  公开号：US8030489B2

  公开（公告）日：2011-10-04