methyl ((S)-2-((S)-N-methyl-2-(((2,2,2-trichloroethoxy)carbonyl)amino)propanamido)pent-4-ynoyl)glycinate | 1332641-12-9

• 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: methyl ((S)-2-((S)-N-methyl-2-(((2,2,2-trichloroethoxy)carbonyl)amino)propanamido)pent-4-ynoyl)glycinate
• CAS: 1332641-12-9
• 化学式: C₁₅H₂₀Cl₃N₃O₆
• 分子量: 444.699
• InChiKey: ZVYMWRSLQYTJDG-UWVGGRQHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.61
• 重原子数：
  27.0
• 可旋转键数：
  8.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  114.04
• 氢给体数：
  2.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  methyl ((S)-2-((S)-N-methyl-2-(((2,2,2-trichloroethoxy)carbonyl)amino)propanamido)pent-4-ynoyl)glycinate 在 4-二甲氨基吡啶 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 生成
  参考文献：
  名称：

  Synthesis and biological evaluation of triazole analogues of antillatoxin

  摘要：

  Antillatoxin 1, a cyclic lipopeptide, is known as an activator of voltage-gated sodium channels and exhibits potent neurotoxicity toward Neuro 2a mouse neuroblastoma cells. To investigate the biological effects of the side-chain structures at C5 and C5' in detail, we planned SAR studies of C5- and C5'-modified antillatoxin analogues. To diversify the structures at the last step of the synthesis, two key intermediates 4 and 6 possessing terminal alkynes at the C5- and C5'-positions were designed and synthesized using two distinct strategies. Sixteen side-chain derivatives were then prepared from 4 and 6 by coupling with a wide variety of azides via click chemistry, and subjected to the cytotoxicity assay. Although almost all of the C5-substituted analogues exhibited no cytotoxicity, the C5'-substituted analogues showed modest cytotoxicity. These results showed that C5' is more tolerant than C5 to structural modifications. The present SAR study will provide valuable information for designing new antillatoxin-based molecular probes for neuroscience research. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.012
• 作为产物：
  描述：

  在 potassium carbonate 、 苯硫酚 、 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-) 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 18.0h， 生成 methyl ((S)-2-((S)-N-methyl-2-(((2,2,2-trichloroethoxy)carbonyl)amino)propanamido)pent-4-ynoyl)glycinate
  参考文献：
  名称：

  Synthesis and biological evaluation of triazole analogues of antillatoxin

  摘要：

  Antillatoxin 1, a cyclic lipopeptide, is known as an activator of voltage-gated sodium channels and exhibits potent neurotoxicity toward Neuro 2a mouse neuroblastoma cells. To investigate the biological effects of the side-chain structures at C5 and C5' in detail, we planned SAR studies of C5- and C5'-modified antillatoxin analogues. To diversify the structures at the last step of the synthesis, two key intermediates 4 and 6 possessing terminal alkynes at the C5- and C5'-positions were designed and synthesized using two distinct strategies. Sixteen side-chain derivatives were then prepared from 4 and 6 by coupling with a wide variety of azides via click chemistry, and subjected to the cytotoxicity assay. Although almost all of the C5-substituted analogues exhibited no cytotoxicity, the C5'-substituted analogues showed modest cytotoxicity. These results showed that C5' is more tolerant than C5 to structural modifications. The present SAR study will provide valuable information for designing new antillatoxin-based molecular probes for neuroscience research. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2011.05.012