3-hydroxy-N-[(1R,4S,7R,11S,14R,17S,20R,24S)-20-[(3-hydroxyquinoline-2-carbonyl)amino]-2,4,12,15,17,25-hexamethyl-3,6,10,13,16,19,23,26-octaoxo-11,24-di(propan-2-yl)-9,22-dioxa-28,29-dithia-2,5,12,15,18,25-hexazabicyclo[12.12.4]triacontan-7-yl]quinoline-2-carboxamide | 1444301-76-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 3-hydroxy-N-[(1R,4S,7R,11S,14R,17S,20R,24S)-20-[(3-hydroxyquinoline-2-carbonyl)amino]-2,4,12,15,17,25-hexamethyl-3,6,10,13,16,19,23,26-octaoxo-11,24-di(propan-2-yl)-9,22-dioxa-28,29-dithia-2,5,12,15,18,25-hexazabicyclo[12.12.4]triacontan-7-yl]quinoline-2-carboxamide
• CAS: 1444301-76-1
• 化学式: C₅₂H₆₄N₁₀O₁₄S₂
• 分子量: 1117.27
• InChiKey: CCWNJHFUQLIZBG-KOPQPNPPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  78
• 可旋转键数：
  6
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  367
• 氢给体数：
  6
• 氢受体数：
  18

反应信息

• 作为产物：
  描述：

  (2S,5R,9S,12R,17R,20S,24R,27S)-5,24-bis(3-hydroxyquinoline-2-carboxamido)-9,20-diisopropyl-2,10,19,27-tetramethyl-12,17-bis(methylamino)-4,8,11,18,21,25-hexaoxo-7,22-dioxa-14,15-dithia-3,10,19,26-tetraazaoctacosanedioic acid 在 N-羟基-7-氮杂苯并三氮唑 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.5h， 生成 3-hydroxy-N-[(1R,4S,7R,11S,14R,17S,20R,24S)-20-[(3-hydroxyquinoline-2-carbonyl)amino]-2,4,12,15,17,25-hexamethyl-3,6,10,13,16,19,23,26-octaoxo-11,24-di(propan-2-yl)-9,22-dioxa-28,29-dithia-2,5,12,15,18,25-hexazabicyclo[12.12.4]triacontan-7-yl]quinoline-2-carboxamide
  参考文献：
  名称：

  Orthogonal Chemistry for the Synthesis of Thiocoraline–Triostin Hybrids. Exploring their Structure–Activity Relationship

  摘要：

  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.

  DOI：

  10.1021/jm4006093

文献信息

• 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.