[(4S)-benzyl-5-hydroxy-(1S)-isobutylpent-(2E)-enyl]carbamic acid tert-butyl ester | 866404-27-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: [(4S)-benzyl-5-hydroxy-(1S)-isobutylpent-(2E)-enyl]carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(E,4S,7S)-7-benzyl-8-hydroxy-2-methyloct-5-en-4-yl]carbamate
• CAS: 866404-27-5
• 化学式: C₂₁H₃₃NO₃
• 分子量: 347.498
• InChiKey: BBUKYXJYQCXOFN-MCBHFWOFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  25
• 可旋转键数：
  10
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  [(4S)-benzyl-5-hydroxy-(1S)-isobutylpent-(2E)-enyl]carbamic acid tert-butyl ester 在 4-二甲氨基吡啶 、 戴斯-马丁氧化剂 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 作用下， 以 二氯甲烷 为溶剂， 反应 29.0h， 生成 Boc-Leu-ψ[(E)-CH=CH]-D-Phe-TEMPO
  参考文献：
  名称：

  Mitochondrial Targeting of Selective Electron Scavengers:  Synthesis and Biological Analysis of Hemigramicidin−TEMPO Conjugates

  摘要：

  Synthetic hemigramicidin S-peptidyl TEMPO conjugates are effectively delivered into cells and mitochondria, where they act as electron scavengers and exert protection against apoptosis. Our delivery approach is based on the use of specific structural signaling features recognizable by cells as mitochondria targeting sequences and offers considerable therapeutic anti-apoptotic potential.

  DOI：

  10.1021/ja053679l
• 作为产物：
  描述：

  acetic acid (2S)-benzyl-(5S)-tert-butoxycarbonylamino-7-methyloct-(3E)-enyl ester 在 potassium carbonate 作用下， 以 甲醇 为溶剂， 反应 5.0h， 以100%的产率得到[(4S)-benzyl-5-hydroxy-(1S)-isobutylpent-(2E)-enyl]carbamic acid tert-butyl ester
  参考文献：
  名称：

  TARGETED NITROXIDE AGENTS

  摘要：

  本文提供了一种对自由基清除有用的组合物和相关方法，具有特定选择性作用于线粒体。这些化合物包括一个连接到线粒体靶向基团的亚硝基含有基团。这些化合物可以交联成二聚体而不丧失活性。本文还提供了一种用于预防、缓解和治疗辐射引起的损伤的方法。该方法包括向患者输送一种如本文所述的化合物，以有效地预防、缓解或治疗辐射引起的损伤。

  公开号：

  US20100035869A1

文献信息

• TARGETED NITROXIDE AGENTS
  申请人：Wipf Peter

  公开号：US20100035869A1

  公开（公告）日：2010-02-11

  Provided herein are compositions and related methods useful for free radical scavenging, with particular selectivity for mitochondria. The compounds comprise a nitroxide-containing group attached to a mitochondria-targeting group. The compounds can be cross-linked into dimers without loss of activity. Also provided herein are methods, for preventing, mitigating and treating damage caused by radiation. The method comprises delivering a compound, as described herein, to a patient in an amount and dosage regimen effective to prevent, mitigate or treat damage caused by radiation.

  本文提供了一种对自由基清除有用的组合物和相关方法，具有特定选择性作用于线粒体。这些化合物包括一个连接到线粒体靶向基团的亚硝基含有基团。这些化合物可以交联成二聚体而不丧失活性。本文还提供了一种用于预防、缓解和治疗辐射引起的损伤的方法。该方法包括向患者输送一种如本文所述的化合物，以有效地预防、缓解或治疗辐射引起的损伤。
• SELECTIVE TARGETING AGENTS FOR MITCOCHONDRIA
  申请人：Wipf Peter

  公开号：US20070161544A1

  公开（公告）日：2007-07-12

  The present invention relates to compositions and methods for providing mitochondria-selective targeting agents covalently linked to desired cargo such as radical scavenging agents. Compositions and methods are disclosed for treating an illness that is caused or associated with cellular damage or dysfunction which is caused by excessive mitochondrial production of reaction oxygen species (ROS). Compositions which act as mitochondria-selective targeting agents using specific structural signaling features recognizable by cells as mitochondrial targeting sequences are discussed. A method for delivering these agents effectively into cells and mitochondria where they act as electron scavengers by way of certain targeting sequences is also disclosed. Mitochondria and cell death by way of apoptosis is inhibited as a result of the ROS-scavenging activity, thereby increasing the survival rate of the patient. In a preferred embodiment, the compositions and methods may be administered therapeutically in the field to patients with profound hemorrhagic shock so that survival could be prolonged until it is feasible to obtain surgical control of the bleeding vessels. In further preferred embodiments, the composition for scavenging radicals in a mitochondrial membrane includes a radical scavenging agent and a membrane active compound having a high affinity with said mitochondrial membrane and associated methods. In another embodiment, the cargo transported by mitochondrial-selective targeting agents may include an inhibitor of nitrous oxide system (NOS) enzyme activity.

  本发明涉及将线粒体选择性靶向剂与所需的货物（如自由基清除剂）共价连接的组合物和方法。揭示了用于治疗由过度线粒体反应氧化物（ROS）产生引起或与细胞损伤或功能障碍相关的疾病的组合物和方法。讨论了作为线粒体选择性靶向剂的组合物，使用特定的结构信号特征，可被细胞识别为线粒体靶向序列。还揭示了一种将这些剂有效地输送到细胞和线粒体内，在那里它们通过某些靶向序列作为电子清除剂起作用的方法。由于ROS清除活性，抑制了线粒体和细胞凋亡，从而增加了患者的生存率。在首选实施例中，这些组合物和方法可以在深度失血性休克的患者中进行治疗，以延长生存时间，直到获得手术控制出血血管。在进一步的首选实施例中，用于清除线粒体膜中自由基的组合物包括具有与线粒体膜高亲和力的膜活性化合物和自由基清除剂，并提供了相关方法。在另一种实施例中，由线粒体选择性靶向剂运输的货物可以包括一种抑制一氧化氮系统（NOS）酶活性的抑制剂。
• US7718603B1
  申请人：——

  公开号：US7718603B1

  公开（公告）日：2010-05-18
• Mitochondrial Targeting of Selective Electron Scavengers:  Synthesis and Biological Analysis of Hemigramicidin−TEMPO Conjugates
  作者：Peter Wipf、Jingbo Xiao、Jianfei Jiang、Natalia A. Belikova、Vladimir A. Tyurin、Mitchell P. Fink、Valerian E. Kagan

  DOI：10.1021/ja053679l

  日期：2005.9.1

  Synthetic hemigramicidin S-peptidyl TEMPO conjugates are effectively delivered into cells and mitochondria, where they act as electron scavengers and exert protection against apoptosis. Our delivery approach is based on the use of specific structural signaling features recognizable by cells as mitochondria targeting sequences and offers considerable therapeutic anti-apoptotic potential.