benzyl N-[(3R,4R,7S,20S,27R,28R,31S,44S)-4,15,28,39-tetramethyl-2,6,13,16,19,26,30,37,40,43-decaoxo-27-(phenylmethoxycarbonylamino)-1,5,12,15,18,25,29,36,39,42-decazapentacyclo[42.4.0.07,12.020,25.031,36]octatetracontan-3-yl]carbamate | 1499188-19-0

• 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: benzyl N-[(3R,4R,7S,20S,27R,28R,31S,44S)-4,15,28,39-tetramethyl-2,6,13,16,19,26,30,37,40,43-decaoxo-27-(phenylmethoxycarbonylamino)-1,5,12,15,18,25,29,36,39,42-decazapentacyclo[42.4.0.07,12.020,25.031,36]octatetracontan-3-yl]carbamate
• CAS: 1499188-19-0
• 化学式: C₅₈H₈₀N₁₂O₁₄
• 分子量: 1169.35
• InChiKey: JBAYLDJYRHWATM-INVHTFHPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  84
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  315
• 氢给体数：
  6
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  benzyl N-[(3R,4R,7S,20S,27R,28R,31S,44S)-4,15,28,39-tetramethyl-2,6,13,16,19,26,30,37,40,43-decaoxo-27-(phenylmethoxycarbonylamino)-1,5,12,15,18,25,29,36,39,42-decazapentacyclo[42.4.0.07,12.020,25.031,36]octatetracontan-3-yl]carbamate 在 盐酸 、 水 作用下， 反应 24.0h， 生成 L-哌啶-2-甲酸
  参考文献：
  名称：

  Total Synthesis of Quinaldopeptin and Its Analogues

  摘要：

  The first total synthesis of quinaldopeptin (1) was accomplished. Our approach to the synthesis of 1 includes the solid-phase peptide synthesis of the linear decapeptide 4 followed by macrocyclization and introduction of the quinoline chromophores 2 at a late stage of the synthesis. As for the preparation of 4, a fragment coupling approach was applied considering the C2 symmetrical structure of 1. Chromophore analogues 22 and 23 and desmethyl analogue 27 were also prepared in a manner similar to the synthesis of 1. Synthetic 1 exhibits a strong cytotoxicity with the IC50 value of 3.2 nM. On the other hand, the activity of 23 and 27 was largely reduced.

  DOI：

  10.1021/jo402267r
• 作为产物：
  描述：

  在 碳酸氢钠 、 3-(二乙氧基邻酰氧基)-1,2,3-苯并三嗪-4-酮 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 96.0h， 以12 mg的产率得到benzyl N-[(3R,4R,7S,20S,27R,28R,31S,44S)-4,15,28,39-tetramethyl-2,6,13,16,19,26,30,37,40,43-decaoxo-27-(phenylmethoxycarbonylamino)-1,5,12,15,18,25,29,36,39,42-decazapentacyclo[42.4.0.07,12.020,25.031,36]octatetracontan-3-yl]carbamate
  参考文献：
  名称：

  喹诺肽肽的合成及生物学评价

  摘要：

  通过Staudinger / aza-Wittig / diastereoselective Ugi三组分反应序列以及无消旋化[5 + 5]偶联和大内酰胺化作用，建立了第二代奎纳肽肽（1）的总合成。发色团类似物26的单晶X射线结构证实了大环的结构和立体化学分配。合成1成功解开超螺旋DNA，形成剂量依赖性的松弛DNA，1至4个dsODN的结合亲和力在相似范围内（K b = 1.45–2.53×10 7 M –1），并且具有序列选择性很微妙。有人建议1就针对人类癌细胞系的细胞毒性活性（IC 50 = 3.2–12 nM）和HIF-1抑制活性而言，其生物学行为与沙雷霉素（2）相似。

  DOI：

  10.1021/jo500039d

文献信息

• Synthesis and Biological Evaluation of Quinaldopeptin
  作者：Katsushi Katayama、Takuya Okamura、Takuya Sunadome、Koji Nakagawa、Hiroshi Takeda、Motoo Shiro、Akira Matsuda、Satoshi Ichikawa

  DOI：10.1021/jo500039d

  日期：2014.3.21

  The second-generation total synthesis of quinaldopeptin (1) was established via a Staudinger/aza-Wittig/diastereoselective Ugi three-component reaction sequence and a racemization-free [5 + 5] coupling and macrolactamization. A single-crystal X-ray structure of the chromophore analogue 26 confirmed the structural and stereochemical assignments of the macrocycle. Synthetic 1 successfully unwound supercoiled

  通过Staudinger / aza-Wittig / diastereoselective Ugi三组分反应序列以及无消旋化[5 + 5]偶联和大内酰胺化作用，建立了第二代奎纳肽肽（1）的总合成。发色团类似物26的单晶X射线结构证实了大环的结构和立体化学分配。合成1成功解开超螺旋DNA，形成剂量依赖性的松弛DNA，1至4个dsODN的结合亲和力在相似范围内（K b = 1.45–2.53×10 7 M –1），并且具有序列选择性很微妙。有人建议1就针对人类癌细胞系的细胞毒性活性（IC 50 = 3.2–12 nM）和HIF-1抑制活性而言，其生物学行为与沙雷霉素（2）相似。
• Total Synthesis of Quinaldopeptin and Its Analogues
  作者：Satoshi Ichikawa、Takuya Okamura、Akira Matsuda

  DOI：10.1021/jo402267r

  日期：2013.12.20

  The first total synthesis of quinaldopeptin (1) was accomplished. Our approach to the synthesis of 1 includes the solid-phase peptide synthesis of the linear decapeptide 4 followed by macrocyclization and introduction of the quinoline chromophores 2 at a late stage of the synthesis. As for the preparation of 4, a fragment coupling approach was applied considering the C2 symmetrical structure of 1. Chromophore analogues 22 and 23 and desmethyl analogue 27 were also prepared in a manner similar to the synthesis of 1. Synthetic 1 exhibits a strong cytotoxicity with the IC50 value of 3.2 nM. On the other hand, the activity of 23 and 27 was largely reduced.