(S)-炔丙基甘氨酸甲酯 | 101925-55-7

• 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
• 中文名称: (S)-炔丙基甘氨酸甲酯
• 英文名称: (S)-propargylglycine methyl ester
• 英文别名: L-propargylglycine methyl ester；Methyl (2S)-2-aminopent-4-ynoate
• CAS: 101925-55-7
• 化学式: C₆H₉NO₂
• 分子量: 127.143
• InChiKey: GHQXMDDXHKPECL-YFKPBYRVSA-N

物化性质

• 沸点：
  191.8±30.0 °C(Predicted)
• 密度：
  1.069±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  9
• 可旋转键数：
  3
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  52.3
• 氢给体数：
  1
• 氢受体数：
  3

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  (2S)-2-氨基-4-戊炔酸	(2S)-2-amino-4-pentynoic acid	23235-01-0	C5H7NO2	113.116

反应信息

• 作为反应物：
  描述：

  (S)-炔丙基甘氨酸甲酯 在 palladium diacetate 吡啶 、 potassium carbonate 、 三苯基膦 作用下， 以 四氢呋喃 为溶剂， 反应 64.0h， 生成 (2S)-methyl 1-(4-methylphenylsulfonyl)-4,5-dihydropyrrole-2-carboxylate
  参考文献：
  名称：

  钯催化的含乙炔氨基酸的环化反应

  摘要：

  对映体纯的含乙炔的α-氨基酸被用作通过Pd介导的环化反应合成各种杂环的通用原料。取决于保护基策略，氨基酸的羧酸盐和胺官能团均可以参与环化，因此分别产生氧杂环（α-氨基内酯）和氮杂环（​​环状α-氨基酸衍生物）。除直接环化外，还成功进行了环化/交叉偶联反应以提供相应的取代的环状氨基酸衍生物。

  DOI：

  10.1002/1615-4169(200201)344:1<70::aid-adsc70>3.0.co;2-1
• 作为产物：
  描述：

  methyl (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)pent-4-ynoate 在 哌啶 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 (S)-炔丙基甘氨酸甲酯
  参考文献：
  名称：

  Propargylglycine-based antimicrobial compounds are targets of TolC-dependent efflux systems in Escherichia coli

  摘要：

  A library of novel L-propargylglycine-based compounds were designed and synthesized with the goal of inhibiting the growth of Gram-negative bacteria by targeting LpxC, a highly conserved Gram-negative enzyme which performs an essential step in the lipid A biosynthetic pathway. These compounds were designed with and without a nucleoside and had varying tail structures, which modulate their lipophilicity. The synthetic scheme was improved compared to previous methods: a methyl ester intermediate was converted to a hydroxamic acid, which obviated the need for a THP protecting group and improved the yields and purity of the final compounds. Antimicrobial activity was observed for non-nucleoside compounds containing a phenyl propargyl ether tail (5) or a biphenyl tail (6). An MIC of 16 mu g/mL was achieved for 6 in Escherichia coli, but inhibition was only possible in the absence of TolC-mediated efflux. Compound 5 had an initial MIC > 160 mu g/mL in E. coli. Enhancing outer membrane permeability or eliminating efflux reduced the MIC modestly to 100 mu g/mL and 80 mu g/mL, respectively. These results highlight the importance of hydrophobicity of this class of compounds in developing LpxC inhibitors, as well as the design challenge of avoiding multidrug efflux activity.

  DOI：

  10.1016/j.bmcl.2019.126875

文献信息

• Chemoenzymatic Synthesis of Triazole-Linked Glycopeptides
  作者：Floris Rutjes、Stan Groothuys、Brian Kuijpers、Peter Quaedflieg、Harlof Roelen、Roel Wiertz、Richard Blaauw、Floris van Delft

  DOI：10.1055/s-2006-942509

  日期：——

  Triazole-linked glycopeptides are prepared by C-terminal elongation of glycoamino acids with proteinogenic amino acids following a chemical or enzymatic coupling protocol. Two orthogonal routes for a chemoenzymatic strategy were explored, involving a click-reaction before amide bond formation or in reverse order. It was found that enzymatic peptide coupling under the influence of alcalase proceeds cleanly and in high yields, while the resulting dipeptides can be efficiently clicked to acetylene- or azide-containing sugars.

  三氮唑联接的糖肽通过糖氨基酸的C端延伸，与蛋白质氨基酸按照化学或酶促耦合协议制备。探索了两条正交路径的化学酶促策略，涉及在酰胺键形成之前或顺序相反的点击反应。研究发现，在碱性蛋白酶的影响下，酶促肽耦合过程顺利进行且产率较高，同时所得的二肽可以高效地与含有炔烃或叠氮的糖发生点击反应。
• [EN] 5-[5-[2-(3,5-BIS(TRIFLUOROMETHYL)PHENYL)-2-METHYLPROPANOYLMETHYLAMINO]-4-(4-FLUORO-2-METHYLPHENYL)]-2-PYRIDINYL-2-ALKYL-PROLINAMIDE AS NK1 RECEPTOR ANTAGONISTS<br/>[FR] 5- [5- [2- (3, 5-BIS (TRIFLUOROMÉTHYL) PHÉNYL) -2-MÉTHYLPROPANOYLMÉTHYLAMINO] -4- (4-FLUORO-2-MÉTHYLPHÉNYL) ] -2-PYRIDINYL-2-ALKYL-PROLINAMIDE, ANTAGONISTES DU RÉCEPTEUR NK1
  申请人：GLAXO WELLCOME MFG PTE LTD

  公开号：WO2009138393A1

  公开（公告）日：2009-11-19

  The invention provides a compound of formula (I) or a pharmaceutically acceptable salt thereof, wherein R is C1-4 alkyl useful in the treatment of diseases and conditions for which antagonism of NK1 receptor is beneficial.

  该发明提供了一种式（I）的化合物或其药用可接受的盐，其中R为C1-4烷基，在治疗需要NK1受体拮抗作用有益的疾病和症状中有用。
• Sonogashira Reaction of Bromofluoropyridinaldoxime Nuclei: Convergent Synthesis of Functionalized 2- and 3-Fluoropyridine Scaffolds
  作者：Jagadeesh Yerri、Rachid Baati

  DOI：10.1002/ejoc.201800608

  日期：2018.8.15

  The palladium catalyzed Sonogashira cross‐coupling of bromofluoropyridinaldoxime with highly functionalized alkynes investigated in this study is fully compatible with unprotected sensitive aldoxime and affords representative underexplored new scaffolds.

  在这项研究中，钯催化的溴氟吡啶并二肟与高度官能化的炔烃的Sonogashira交叉偶联与未保护的敏感醛肟完全相容，并提供了开发不足的代表性新支架。
• Electrochemical C−H/N−H Functionalization for the Synthesis of Highly Functionalized (Aza)indoles
  作者：Zhong‐Wei Hou、Zhong‐Yi Mao、Huai‐Bo Zhao、Yared Yohannes Melcamu、Xin Lu、Jinshuai Song、Hai‐Chao Xu

  DOI：10.1002/anie.201602616

  日期：2016.8

  their prevalence in nature and their broad utility in pharmaceutical industry. Reported herein is an unprecedented noble‐metal‐ and oxidant‐free electrochemical method for the coupling of (hetero)arylamines with tethered alkynes to synthesize highly functionalized indoles, as well as the more challenging azaindoles.

  吲哚和氮杂吲哚由于其在自然界中的普遍性及其在制药工业中的广泛应用而成为最重要的杂环。本文报道了一种前所未有的无贵金属，无氧化剂的电化学方法，用于将（杂）芳基胺与链状炔烃偶联，以合成高度官能化的吲哚以及更具挑战性的氮吲哚。
• 6-SUBSTITUTED 3-FLUORO-2-PYRIDINALDOXIME, 3-FLUORO-2-PYRIDINE HYDROXAMIC ACID, AND 3-FLUORO-2-PYRIDINAMIDOXIME SCAFFOLDS
  申请人：CENTRE NATIONAL DE LA RECHERCHE SCIENTIFIQUE

  公开号：EP3473618A1

  公开（公告）日：2019-04-24

  The present invention relates to a compound of formula (I), as well as to a process for preparing the compounds of formula (I) by a chemoselective Sonogashira reaction. It also relates to a pharmaceutical composition comprising at least one compound of formula (I) and at least one pharmaceutically acceptable support. Finally, it relates to the use of such a compound as a medicine, preferably in the treatment of a nervous and/or respiratory failure due to intoxication with at least one organophosphorous nerve agent; in the treatment of neurological diseases such as Alzheimer's disease; and/or in the treatment of cancer; and/or for use as antiviral drug.

  本发明涉及一种化合物的公式(I)，以及通过化学选择性Sonogashira反应制备该化合物的方法。还涉及一种包含至少一种公式(I)化合物和至少一种药学上可接受的辅助物质的药物组合物。最后，涉及将这种化合物用作药物，优选用于治疗由至少一种有机磷神经毒剂中毒引起的神经和/或呼吸衰竭；治疗神经系统疾病，如阿尔茨海默病；和/或治疗癌症；和/或用作抗病毒药物。