N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]-L-valine | 866832-83-9

• 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: N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]-L-valine
• 英文别名: Dde-Val-OH；(2S)-2-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethylamino]-3-methylbutanoic acid
• CAS: 866832-83-9
• 化学式: C₁₅H₂₃NO₄
• 分子量: 281.352
• InChiKey: VZDSFWRJZCZKJI-ZDUSSCGKSA-N

物化性质

• 沸点：
  439.2±45.0 °C(Predicted)
• 密度：
  1.125±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.92
• 重原子数：
  20.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  83.47
• 氢给体数：
  2.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]-L-valine 在 palladium on activated charcoal 氢气 、 N,N'-二异丙基碳二亚胺 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 54.17h， 生成 N-(9H-fluoren-9-ylmethoxycarbonyl)-O-{N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]-L-valyl}-D-serine
  参考文献：
  名称：

  Efficient Solid-Phase-Based Total Synthesis of the Bisintercalator TANDEM

  摘要：

  In this article, the first solid-phase-based total synthesis of TANDEM, a synthetic analogue of triostin A, is described. In initial studies, the synthesis incorporated depsipeptide formation, introduction of chromophores, and disulfide bond formation on the solid phase, prior to a final solution-phase macrolactamization, to give the target molecule. Although pure TANDEM was obtained in an overall yield comparable to those for all syntheses to date, the yield of the final cyclization was low (11%). A more efficient approach involved removal from the solid phase prior to disulfide bond formation. The resulting linear peptide underwent macrolactamization under mild conditions and high dilution. Final disulfide bond formation was essentially quantitative and gave the target molecule, TANDEM, in an overall yield of 18%. The final compound was assessed for its ability to bind to 5'-TpA sequences on DNA by DNase I footprinting. This efficient synthesis sets the stage for a study of the structure-activity relationship of TANDEM and the natural product triostin A, with analogues containing "point mutations" at every site within the cyclic compounds.

  DOI：

  10.1021/jo050959a
• 作为产物：
  描述：

  5,5-二甲基-1,3-环己二酮 在 4-二甲氨基吡啶 、 三乙胺 、 N,N-二异丙基乙胺 作用下， 以 乙醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 N-[1-(4,4-dimethyl-2,6-dioxocyclohexylidene)ethyl]-L-valine
  参考文献：
  名称：

  针对EphA2的一珠两化合物硫醚桥连大环γ-AA肽筛选库

  摘要：

  识别可识别肽或蛋白质的分子配体的识别很重要，但在化学生物学和生物医学领域提出了根本性的挑战。环状拟肽文库的开发是稀缺的，因此很少有针对蛋白质靶标的环状拟肽配体的发现。在本文中，我们报告了基于一类新型的大环拟肽γ-AA肽的前所未有的一珠两化合物（OBTC）组合文库。在该文库中，我们利用了由Dde保护的α-氨基酸合成的编码肽标签，这些标签与γ-AA肽的固相合成正交。利用硫醚键，发现所需的大环γ-AA肽对于配体鉴定是有效的。K d = 81 nM）和有效拮抗的EphA2介导的信号转导。大环拟肽文库的这种新方法可能会导致生物大分子表面识别和功能调节的新型平台。

  DOI：

  10.1021/acs.jmedchem.7b01280

文献信息

• One-bead-two-compound macrocyclic library and methods of preparation and use
  申请人：University of South Florida

  公开号：US10738082B2

  公开（公告）日：2020-08-11

  A one-bead-two-compound combinatorial synthesis technique provides libraries of macrocyclic peptidomimetic compounds and compositions with use as ligands for the Ephrin type-A receptor 2 (EphA2). The one-bead-two-compound technique and libraries of macrocyclic compounds are useful as research tools in drug discovery and/or to treat or prevent a range of diseases or disorders.

  一珠二化合物组合合成技术提供了可用作Ephrin-A型受体2（EphA2）配体的大环拟肽化合物库和组合物。单珠双化合物技术和大环化合物文库可作为药物发现的研究工具和/或用于治疗或预防一系列疾病或失调。
• ONE-BEAD-TWO-COMPOUND MACROCYCLIC LIBRARY AND METHODS OF PREPARATION AND USE
  申请人：University of South Florida

  公开号：US20200377552A1

  公开（公告）日：2020-12-03

  A one-bead-two-compound combinatorial synthesis technique provides libraries of macrocyclic peptidomimetic compounds and compositions with use as ligands for the Ephrin type-A receptor 2 (EphA2). The one-bead-two-compound technique and libraries of macrocyclic compounds are useful as research tools in drug discovery and/or to treat or prevent a range of diseases or disorders.
• One-Bead–Two-Compound Thioether Bridged Macrocyclic γ-AApeptide Screening Library against EphA2
  作者：Yan Shi、Sridevi Challa、Peng Sang、Fengyu She、Chunpu Li、Geoffrey M. Gray、Alekhya Nimmagadda、Peng Teng、Timothy Odom、Yan Wang、Arjan van der Vaart、Qi Li、Jianfeng Cai

  DOI：10.1021/acs.jmedchem.7b01280

  日期：2017.11.22

  library, we utilized the coding peptide tags synthesized with Dde-protected α-amino acids, which were orthogonal to solid phase synthesis of γ-AApeptides. Employing the thioether linkage, the desired macrocyclic γ-AApeptides were found to be effective for ligand identification. Screening the library against the receptor tyrosine kinase EphA2 led to the discovery of one lead compound that tightly bound

  识别可识别肽或蛋白质的分子配体的识别很重要，但在化学生物学和生物医学领域提出了根本性的挑战。环状拟肽文库的开发是稀缺的，因此很少有针对蛋白质靶标的环状拟肽配体的发现。在本文中，我们报告了基于一类新型的大环拟肽γ-AA肽的前所未有的一珠两化合物（OBTC）组合文库。在该文库中，我们利用了由Dde保护的α-氨基酸合成的编码肽标签，这些标签与γ-AA肽的固相合成正交。利用硫醚键，发现所需的大环γ-AA肽对于配体鉴定是有效的。K d = 81 nM）和有效拮抗的EphA2介导的信号转导。大环拟肽文库的这种新方法可能会导致生物大分子表面识别和功能调节的新型平台。
• Efficient Solid-Phase-Based Total Synthesis of the Bisintercalator TANDEM
  作者：John P. Malkinson、Michael K. Anim、Mire Zloh、Mark Searcey、Andrew J. Hampshire、Keith R. Fox

  DOI：10.1021/jo050959a

  日期：2005.9.1

  In this article, the first solid-phase-based total synthesis of TANDEM, a synthetic analogue of triostin A, is described. In initial studies, the synthesis incorporated depsipeptide formation, introduction of chromophores, and disulfide bond formation on the solid phase, prior to a final solution-phase macrolactamization, to give the target molecule. Although pure TANDEM was obtained in an overall yield comparable to those for all syntheses to date, the yield of the final cyclization was low (11%). A more efficient approach involved removal from the solid phase prior to disulfide bond formation. The resulting linear peptide underwent macrolactamization under mild conditions and high dilution. Final disulfide bond formation was essentially quantitative and gave the target molecule, TANDEM, in an overall yield of 18%. The final compound was assessed for its ability to bind to 5'-TpA sequences on DNA by DNase I footprinting. This efficient synthesis sets the stage for a study of the structure-activity relationship of TANDEM and the natural product triostin A, with analogues containing "point mutations" at every site within the cyclic compounds.