(2S,4S)-2-trifluoromethyloxazolidine-4-carboxylic acid methyl ester | 1228376-89-3

• 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: (2S,4S)-2-trifluoromethyloxazolidine-4-carboxylic acid methyl ester
• 英文别名: (2S)-L-Ψ^CF3,HPro-OMe；methyl (2S,4S)-2-(trifluoromethyl)-1,3-oxazolidine-4-carboxylate
• CAS: 1228376-89-3
• 化学式: C₆H₈F₃NO₃
• 分子量: 199.13
• InChiKey: IQZAFRMVBOVFQL-UCORVYFPSA-N

物化性质

• 沸点：
  182.0±40.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  47.6
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2S,4S)-2-trifluoromethyloxazolidine-4-carboxylic acid methyl ester 在 水 、 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 4.0h， 以470 mg的产率得到lithium;(2S,4S)-2-(trifluoromethyl)-1,3-oxazolidine-4-carboxylate
  参考文献：
  名称：

  Synthesis of 2-Trifluoromethyl-1,3-oxazolidines as Hydrolytically Stable Pseudoprolines

  摘要：

  Trifluoromethyl group containing oxazolidines (Fox) are conveniently synthesized by condensation of serine esters with trifluoroacetaldehyde hemiacetal or trifluoroacetone. These oxazolidines can undergo N-acylation and amidification reactions and are completely configurationally and hydrolytically stable. Therefore, they can be considered as highly valuable proline surrogates (Tfm-pseudoprolines).

  DOI：

  10.1021/jo100518t
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 、 1-乙氧基-2,2,2-三氟乙醇 在 4-甲基苯磺酸吡啶 作用下， 以 甲苯 为溶剂， 以65%的产率得到(2S,4S)-2-trifluoromethyloxazolidine-4-carboxylic acid methyl ester
  参考文献：
  名称：

  Synthesis of 2-Trifluoromethyl-1,3-oxazolidines as Hydrolytically Stable Pseudoprolines

  摘要：

  Trifluoromethyl group containing oxazolidines (Fox) are conveniently synthesized by condensation of serine esters with trifluoroacetaldehyde hemiacetal or trifluoroacetone. These oxazolidines can undergo N-acylation and amidification reactions and are completely configurationally and hydrolytically stable. Therefore, they can be considered as highly valuable proline surrogates (Tfm-pseudoprolines).

  DOI：

  10.1021/jo100518t

文献信息

• Homochiral versus Heterochiral Trifluoromethylated Pseudoproline Containing Dipeptides: A Powerful Tool to Switch the Prolyl-Amide Bond Conformation
  作者：Grégory Chaume、Julien Simon、Nathalie Lensen、Julien Pytkowicz、Thierry Brigaud、Emeric Miclet

  DOI：10.1021/acs.joc.7b01944

  日期：2017.12.15

  applications in supramolecular chemistry. Due to its nature, the peptide bond undergoes a spontaneous cis–trans isomerism, and the cis isomers are much more difficult to stabilize than the trans forms. By using oxazolidine-based pseudoprolines (ΨPro) substituted by a trifluoromethyl group, we show that the cis peptide bond can be readily switched from 0% to 100% in Xaa-ΨPro dipeptides. Our results prove

  约束肽的设计对于生物活性化合物的开发以及在超分子化学中的应用至关重要。由于其性质，肽键会经历自发的顺-反异构，并且顺式异构体比反式更难稳定。通过使用被三氟甲基取代的基于恶唑烷的假脯氨酸（ΨPro），我们显示了Xaa-ΨPro二肽中的顺式肽键很容易从0％切换到100％。我们的研究结果证明，改变C的构造α中的Xaa或ΨPro足以颠倒顺式：反式在改变Xaa侧链的性质的同时，种群数量微调了构象比。此外，在恶唑烷环的褶皱与肽键构象之间发现强烈的相关性。这一发现突出了三氟甲基在稳定肽键几何形状中的作用。我们预期这样的模板对于限制更长的肽的骨架几何结构将是非常有用的。
• Incorporation of Trifluoromethylated Proline and Surrogates into Peptides: Application to the Synthesis of Fluorinated Analogues of the Neuroprotective Glycine-Proline-Glutamate (GPE) Tripeptide
  作者：Julien Simon、Julien Pytkowicz、Nathalie Lensen、Grégory Chaume、Thierry Brigaud

  DOI：10.1021/acs.joc.6b00704

  日期：2016.7.1

  pseudoprolines and oxazolidines has been achieved. As an application, the synthesis of a new class of fluorinated analogues of the neuroprotective tripeptide glycine-proline-glutamate (GPE) is reported. These analogues have been elaborated from a panel of five-membered ring trifluoromethylated amino acids (Tfm-AAs) through the coupling reaction with a glutamate residue at the C-terminus and a glycine at

  已经实现了将高度受阻和弱亲核的三氟甲基化脯氨酸，假脯氨酸和恶唑烷掺入肽链中。作为一种应用，报道了新型的神经保护性三肽甘氨酸-脯氨酸-谷氨酸（GPE）的氟化类似物的合成。这些类似物已经通过一组五元环三氟甲基化氨基酸（Tfm-AAs）通过与C端的谷氨酸残基和N端的甘氨酸的偶联反应进行了精心设计。尽管在标准条件下可以方便地在氟化氨基酸的C端进行肽偶联反应，但在高度失活的N-终端位置被证明存在更多问题。需要进行方法学研究来确定这种困难的肽偶联的合适反应条件。
• Incorporation of CF₃–Pseudoprolines into Peptides: A Methodological Study
  作者：Grégory Chaume、Julien Simon、Caroline Caupène、Nathalie Lensen、Emeric Miclet、Thierry Brigaud

  DOI：10.1021/jo401494q

  日期：2013.10.18

  The peptide coupling reactions allowing the incorporation of trifluoromethyl substituted oxazolidine-type pseudoprolines (CF3-Psi Pro) into peptide chains have been studied. While standard protocols can be used for the peptide coupling reaction at the C-terminal position of the CF3-Psi Pro, acid chloride activation has to be used for the peptide coupling reaction at the N-terminal position to overcome the decrease of nucleophilicity of the CF3-Psi Pro. We demonstrate that the N-amidification of a diastereomeric mixture of CF3-Psi Pro using Fmoc-protected amino acid chloride without base gave the corresponding dipeptides as a single diastereomer (6 examples). The ratio of the cis and trans amide bond conformers was determined by NMR study, highlighting the role of the Xaa side chains in the control of the peptide backbone conformation. Finally a tripeptide bearing a central CF3-Psi Pro has been successfully synthesized.
• Synthesis of 2-Trifluoromethyl-1,3-oxazolidines as Hydrolytically Stable Pseudoprolines
  作者：Grégory Chaume、Olivier Barbeau、Philippe Lesot、Thierry Brigaud

  DOI：10.1021/jo100518t

  日期：2010.6.18

  Trifluoromethyl group containing oxazolidines (Fox) are conveniently synthesized by condensation of serine esters with trifluoroacetaldehyde hemiacetal or trifluoroacetone. These oxazolidines can undergo N-acylation and amidification reactions and are completely configurationally and hydrolytically stable. Therefore, they can be considered as highly valuable proline surrogates (Tfm-pseudoprolines).