[L-(trans)]-N-(t-butoxycarbonyl)-2-[2'-carboxy-2'-methyl-1'-ethenyl]pyrrolidine | 179040-16-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: [L-(trans)]-N-(t-butoxycarbonyl)-2-[2'-carboxy-2'-methyl-1'-ethenyl]pyrrolidine
• 英文别名: (S,E)-3-(1-(tert-butoxycarbonyl)pyrrolidin-2-yl)-2-methylacrylic acid；(S)-3-(1-(tert-Butoxycarbonyl)pyrrolidin-2-yl)-2-methylacrylic acid；(E)-2-methyl-3-[(2S)-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidin-2-yl]prop-2-enoic acid
• CAS: 179040-16-5
• 化学式: C₁₃H₂₁NO₄
• 分子量: 255.314
• InChiKey: ZDWMXFYVQVMICU-DDXVTDLHSA-N

物化性质

• 沸点：
  389.1±35.0 °C(Predicted)
• 密度：
  1.194±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.69
• 拓扑面积：
  66.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  [L-(trans)]-N-(t-butoxycarbonyl)-2-[2'-carboxy-2'-methyl-1'-ethenyl]pyrrolidine 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 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 生成 (S)-4-Methyl-2-[2-((E)-2-methyl-3-(S)-pyrrolidin-2-yl-acryloylamino)-acetylamino]-pentanoic acid methyl ester
  参考文献：
  名称：

  Nucleation of β-Hairpin Structures with Cis Amide Bonds in E-Vinylogous Proline-Containing Peptides

  摘要：

  Synthesis and conformational studies of peptides containing the E-vinylogous prolines 1 (VPro1) and 2 (VPro2), Boc-Ala-Val-VPro1-Xaa-Leu-OMe (3, Xaa = Gly; 4, Xaa = Phe), Boc-Ala-Val-VPro2-Xaa-Leu-OMe (5, Xaa = Gly; 6, Xaa = Phe), Boc-Leu-Ile-Val-VPro1-Xaa-Leu-OMe (7, Xaa = Gly; 8, Xaa = Phe), and Boc-Leu-Ile-Val-VPro2-Xaa-Leu-OMe (9, Xaa = Gly; 10, Xaa = Phe), were carried out. It has been shown that both VPro1 and VPro2 lead to the formation of 12-membered intramolecularly hydrogen bonded structures very similar to type VI beta-turns with a cis Xaa-VPro amide bond in the major conformers in all the peptides 3-10, resulting in the nucleation of beta-hairpin type structures in these molecules in CDCl3.

  DOI：

  10.1021/jo034361j
• 作为产物：
  描述：

  tert-butyl (2S)-2-[(1R,2R)-1-hydroxy-2-methyl-3-[(4R,5S)-4-methyl-2-oxo-5-phenyl-1,3-oxazolidin-3-yl]-3-oxopropyl]pyrrolidine-1-carboxylate 在 lithium hydroxide 、 双氧水 、 sodium hydride 、 sodium sulfite 、 碘甲烷 作用下， 以 四氢呋喃 为溶剂， 反应 69.0h， 生成 [L-(trans)]-N-(t-butoxycarbonyl)-2-[2'-carboxy-2'-methyl-1'-ethenyl]pyrrolidine
  参考文献：
  名称：

  The Dolastatins; 18: Stereospecific Synthesis of Dolaproine

  摘要：

  从海兔 Dolabella auricularia 中分离出来的 Dolastatin 10 (1) 已被证明是一种非常有前途的抗肿瘤物质。这种新的重要多肽的合成已经完成。然而，有必要对其三个手性中心多拉普罗ine (2a) 单元进行更方便的立体选择性合成。通过采用以下关键反应步骤，这一难题得到了切实可行的解决。手性噁唑烷酮 5 在 -75°C 下与 S-脯氨醛 4 缩合，使用三酸二丁基硼引导醛醇反应的立体化学过程。产物的甲基化（6，收率 60-80%）和酰胺的裂解（收率分别为 83% 和 93%）完成了 N-Boc-dolaproine（2b）的简便路线。本文讨论了醛醇反应和恶唑烷酮酰胺裂解的相关方面。

  DOI：

  10.1055/s-1996-4296

文献信息

• Stereoselective synthesis of vinylogous peptides
  作者：Claude Grison、Stéphane Genève、Etienne Halbin、Philippe Coutrot

  DOI：10.1016/s0040-4020(01)00433-1

  日期：2001.6

  A trans or cis ethenyl group has been inserted between the α-carbon and the carboxyl group of α-aminoacids by Horner stereoselective olefination of α-aminoaldehydes. Numerous pure cis and trans vinylogous α-aminoacids have been obtained thus and coupled with aminopartners by classical methods. The versatility of the method was illustrated by the preparation of a [trans vinylogous-Gly3]Leu-enkephalin

  通过α-氨基醛的霍纳立体选择性烯化，将反式或顺式乙烯基插入α-氨基酸的α-碳和羧基之间。因此已经获得了许多纯的顺式和反式乙烯基α-氨基酸，并通过经典方法与氨基配偶体偶联。该方法的多功能性通过制备[反式乙烯基-Gly 3 ]亮脑啡肽来说明。
• Structural Investigation of “cis” and “trans” Vinylogous Peptides:  <i>cis</i>-Vinylog Turn in Folded <i>cis</i>-Vinylogous Peptides, an Excellent Mimic of the Natural β-Turn
  作者：Claude Grison、Philippe Coutrot、Stéphane Genève、Claude Didierjean、Michel Marraud

  DOI：10.1021/jo051483y

  日期：2005.12.1

  Various sequences of modified peptides including those containing a cis- or trans-vinylogous residue have been studied using X-ray diffraction in the solid state and 1H NMR and IR spectroscopy in solution. A cis-vinylogous residue promotes an NH to CO intramolecular H-bond, closing a nine-membered pseudocycle that stabilizes a folded moiety that we proposed to name the cis-vinylogous turn. A trans-vinylogous

  使用固态X射线衍射以及溶液中的1 H NMR和IR光谱研究了修饰的肽的各种序列，包括那些含有顺式或反式乙烯基残基的肽。甲顺-vinylogous残基促进了NH到CO分子内氢键，关闭九元pseudocycle的稳定，我们提出以命名折叠部分顺-vinylogous转弯。甲反-vinylogous残基涉及伸展构象。两个连续的乙烯基残基保持其自身的结构倾向：“ Xaa tr ”-“ Xaa cis ”或“ Xaa cis ”-“ Xaa tr”“”序列被单折叠，而“ Xaa cis ”-“ Xaa cis ”序列被双折叠。具有全反式或全顺式或交替的顺式-反式基序的寡聚乙烯可能构成新型的折叠剂。
• CYTOTOXIC AND ANTI-MITOTIC COMPOUNDS, AND METHODS OF USING THE SAME
  申请人：CDRD Ventures, Inc.

  公开号：US20160075735A1

  公开（公告）日：2016-03-17

  Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

  本发明揭示了具有细胞毒性和/或抗有丝分裂活性的化合物。本发明还揭示了与制备和使用此类化合物相关的方法，以及包含此类化合物的制药组合物。还揭示了具有以下结构的组合物：(T)-(L)-(D)，其中(T)是靶向基团，(L)是可选的连接基团，(D)是具有细胞毒性和/或抗有丝分裂活性的化合物。
• Cytotoxic and anti-mitotic compounds, and methods of using the same
  申请人：ZYMEWORKS INC.

  公开号：US10414822B2

  公开（公告）日：2019-09-17

  Compounds having cytotoxic and/or anti-mitotic activity are disclosed. Methods associated with preparation and use of such compounds, as well as pharmaceutical compositions comprising such compounds, are also disclosed. Also disclosed are compositions having the structure: (T)-(L)-(D), wherein (T) is a targeting moiety, (L) is an optional linker, and (D) is a compound having cytotoxic and/or anti-mitotic activity.

  本研究公开了具有细胞毒性和/或抗有丝分裂活性的化合物。还公开了与制备和使用此类化合物相关的方法，以及包含此类化合物的药物组合物。还公开了具有以下结构的组合物：(T)-(L)-(D)，其中(T)是靶向分子，(L)是任选连接体，(D)是具有细胞毒性和/或抗有丝分裂活性的化合物。
• Catalytic hydrogenation of vinylogous peptides: a route towards γ-peptide foldamers
  作者：Claude Grison、Stéphane Genève、Stéphanie Claudel、Philippe Coutrot、Michel Marraud

  DOI：10.1016/s0040-4039(03)00272-7

  日期：2003.3

  Catalytic hydrogenation over Pd/C of vinylogous aminoacids and aminoamides has been studied. The configuration of the ethylenic bond has an important effect on the diastereoselectivity. The higher selectivity is observed with the E-vinylogous aminoamides. The conformational preferences of the alpha,gamma-disubstituted gamma-peptides have been determined. The 2S,4S-gamma-peptide moiety induces a beta-like folded structure stabilized by an intramolecular hydrogen bond, whereas the 2S,4R-diastereomer assumes an open structure. (C) 2003 Elsevier Science Ltd. All rights reserved.