Alloc-NMe-Cys(Acm)-OH | 1001851-99-5

• 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: Alloc-NMe-Cys(Acm)-OH
• 英文别名: (2R)-3-(acetamidomethylsulfanyl)-2-[methyl(prop-2-enoxycarbonyl)amino]propanoic acid
• CAS: 1001851-99-5
• 化学式: C₁₁H₁₈N₂O₅S
• 分子量: 290.34
• InChiKey: IDPOZWKVDIUWQP-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  121
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Alloc-NMe-Cys(Acm)-OH 、 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 Methanaminium,N-[(dimethylamino)(3H-1,2,3-triazolo[4,5-b]pyridin-3-yloxy)methylene]-N-methyl-, hexafluorophosphate(1-) 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.58h， 生成
  参考文献：
  名称：

  NMe Amide as a Synthetic Surrogate for the Thioester Moiety in Thiocoraline

  摘要：

  Bridged N-methyl amides are used as isosteres for depsi and thiodepsi bonds in thiocoraline. The introduction of NMe-amides in bridges mimics the thioester bonds without imposing steric hindrance and allows conservation of the hydrogen bonding map of the natural product. NMe-azathiocoraline was constructed by solid-phase N-methylation of the side chain of diaminopropionic acid (Dap). The three consecutive N-methyl amino acids could be coupled in good yields by using HATU/HOAt/DIEA in DMF, and the final octapeptide was also obtained on solid phase following a 4 + 4 fragment coupling approach. NMe-azathiocoraline (NMA) displayed nanomolar activity in the same order as the natural product and the same mode of action. In fact, modeling of NMe-azathiocoraline bonded to a TCGA sequence showed how the methyl groups remained further away from the DNA strand without changing the recognition pattern of thiocoraline. Moreover, NMe-azathiocoraline displayed an increased stability in human serum as compared to the parent natural product. This approach could be used in other depsipeptides and side chain to side chain cyclic peptides.

  DOI：

  10.1021/jm800784k

文献信息

• Oxathiocoraline: Lessons to be Learned from the Synthesis of Complex<i>N</i>-Methylated Depsipeptides
  作者：Núria Bayó-Puxan、Judit Tulla-Puche、Fernando Albericio

  DOI：10.1002/ejoc.200900259

  日期：2009.6

  Investigations into the synthesis of oxathiocoraline, a bicyclic depsipeptide with C2 symmetry, revealed a number of unexpected side-reactions that could not be circumvented by classical or standard means. This cyclodepsipeptide has a large number of N-methyl amino acids coexisting with two ester bonds and also shows a branched structure; these features hinder its synthesis. In addition, complexity

  对 oxathiocoraline（一种具有 C2 对称性的双环缩酚肽）合成的研究揭示了许多传统或标准方法无法避免的意外副反应。这种环缩肽含有大量的N-甲基氨基酸并以两个酯键共存，也呈现支链结构；这些特征阻碍了它的合成。此外，由于存在大量非市售半胱氨酸和杂环部分，复杂性进一步增加。在这里，我们描述了在尝试合成环缩肽时应解决的一般问题，例如防止或最小化二酮哌嗪形成、β-消除和氧化副产物的策略。最佳设计包括合适的固体支持物，
• Orthogonal Chemistry for the Synthesis of Thiocoraline–Triostin Hybrids. Exploring their Structure–Activity Relationship
  作者：Judit Tulla-Puche、Sara Auriemma、Chiara Falciani、Fernando Albericio

  DOI：10.1021/jm4006093

  日期：2013.7.11

  The natural compounds triostin and thiocoraline are potent antitumor agents that act as DNA bisintercalators. From a pharmaceutical point of view, these compounds are highly attractive although they present a low pharmacokinetic profile, in part due to their low solubility. Synthetically, they represent a tour de force because no robust strategies have been developed to access a broad range of these bicyclic (depsi)peptides in a straightforward manner. Here we describe solid-phase strategies to synthesize new bisintercalators, such as thiocoraline triostin hybrids, as well is analogues bearing soluble tags. Orthogonal protection schemes (up to, five from: Fmoc, Boc Alloc, pNZ, o-NBS, and Troc), together with the right concourse of the coupling reagents (HOSu, HOBt, HOAt, Oxyma, EDC, DIPCDI, PyAOP, PyBOP, HATU, COMU), were crucial to establish the synthetic plan. In vitro studies and structure activity relationships have been shown trends in the structure activity relationship that Will facilitate the design of new bisintercalators.
• <i>N</i>Me Amide as a Synthetic Surrogate for the Thioester Moiety in Thiocoraline
  作者：Judit Tulla-Puche、Eleonora Marcucci、Elisabet Prats-Alfonso、Núria Bayó-Puxan、Fernando Albericio

  DOI：10.1021/jm800784k

  日期：2009.2.12

  Bridged N-methyl amides are used as isosteres for depsi and thiodepsi bonds in thiocoraline. The introduction of NMe-amides in bridges mimics the thioester bonds without imposing steric hindrance and allows conservation of the hydrogen bonding map of the natural product. NMe-azathiocoraline was constructed by solid-phase N-methylation of the side chain of diaminopropionic acid (Dap). The three consecutive N-methyl amino acids could be coupled in good yields by using HATU/HOAt/DIEA in DMF, and the final octapeptide was also obtained on solid phase following a 4 + 4 fragment coupling approach. NMe-azathiocoraline (NMA) displayed nanomolar activity in the same order as the natural product and the same mode of action. In fact, modeling of NMe-azathiocoraline bonded to a TCGA sequence showed how the methyl groups remained further away from the DNA strand without changing the recognition pattern of thiocoraline. Moreover, NMe-azathiocoraline displayed an increased stability in human serum as compared to the parent natural product. This approach could be used in other depsipeptides and side chain to side chain cyclic peptides.