methyl pent-4-enoyl-L-prolinate | 133301-21-0

• 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 pent-4-enoyl-L-prolinate
• 英文别名: methyl (2S)-1-pent-4-enoylpyrrolidine-2-carboxylate
• CAS: 133301-21-0
• 化学式: C₁₁H₁₇NO₃
• 分子量: 211.261
• InChiKey: WBOGQUKEGZLLML-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  15
• 可旋转键数：
  5
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.64
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  methyl pent-4-enoyl-L-prolinate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 水 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 17.5h， 生成
  参考文献：
  名称：

  Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors

  摘要：

  Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure- activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, beta 5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.

  DOI：

  10.1021/acs.jmedchem.8b00819
• 作为产物：
  描述：

  4-戊烯酸 、 L-脯氨酸甲酯盐酸盐 在 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 7.0h， 以92%的产率得到methyl pent-4-enoyl-L-prolinate
  参考文献：
  名称：

  Development of Macrocyclic Peptides Containing Epoxyketone with Oral Availability as Proteasome Inhibitors

  摘要：

  Macrocyclization has been frequently utilized for optimizing peptide or peptidomimetic-based compounds. In an attempt to obtain potent, metabolically stable, and orally available proteasome inhibitors, 30 oprozomib-derived macrocyclic peptides with structural diversity in their N-terminus and linker were successively designed and synthesized for structure- activity relationship (SAR) studies. As a consequence, the macrocyclic peptides with N-methyl-pyrazole (24p, 24x), imidazole (24t), and pyrazole (24v) as their respective N-termini exhibited favorable in vitro activity and metabolic stability, which translated into their potent in vivo proteasome inhibitory activity after oral administration. In particular, compound 24v, as the most distinguished one among this series, displayed excellent chymotrypsin-like (ChT-L, beta 5) inhibitory potency (IC50 = 16 nM), low nanomolar antiproliferative activity against all three of the tested cell lines, and superior metabolic stability in mouse liver microsome (MLM), as well as favorable inhibition against ChT-L compared to that of oprozomib in BABL/c mice following po administration at a comparatively low dose, thereby representing a promising candidate for further development.

  DOI：

  10.1021/acs.jmedchem.8b00819

文献信息

• Anodic amide oxidations: Fundamental studies concerning the annulation of six- and seven-membered rings onto amines
  作者：Kevin D. Moeller、Scott L. Rothfus、Poh Lee Wong

  DOI：10.1016/s0040-4020(01)87048-4

  日期：1991.1

  electrochemically based annulation procedure for fusing six- and seven-membered rings onto amines has been examined. Both monosubstituted olefins and acetylenes were found to be good nucleophiles for annulating seven-membered rings onto amines. Disubstituted olefins and acetylenes appear to be good nucleophiles for completing the annulation of six-membered rings onto amines. In addition, the compatibility of

  已经研究了烯烃和炔属亲核试剂与用于将六元和七元环融合到胺上的基于电化学的环化程序的相容性。发现单取代的烯烃和乙炔都是将七元环环合到胺上的良好亲核试剂。二取代的烯烃和乙炔似乎是完成六元环在胺上环化的良好亲核试剂。此外，还研究了几种脯氨酸衍生物与环合程序的相容性。
• Building Functionalized Peptidomimetics:  Use of Electroauxiliaries for Introducing <i>N</i>-Acyliminium Ions into Peptides
  作者：Haizhou Sun、Connor Martin、David Kesselring、Rebecca Keller、Kevin D. Moeller

  DOI：10.1021/ja064737l

  日期：2006.10.1

  A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.