| 911368-28-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• CAS: 911368-28-0
• 化学式: C₆₇H₉₃N₃O₂₀
• 分子量: 1260.48
• InChiKey: QEWZENSJZCWZLA-SHLATLBXSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.39
• 重原子数：
  90.0
• 可旋转键数：
  12.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.55
• 拓扑面积：
  373.05
• 氢给体数：
  14.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  在 哌啶 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 生成
  参考文献：
  名称：

  Large Molecular Assembly of Amphotericin B Formed in Ergosterol-Containing Membrane Evidenced by Solid-State NMR of Intramolecular Bridged Derivative

  摘要：

  Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-C-13, N-15] glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of AmB aggregation by ergosterol.

  DOI：

  10.1021/ja063433w
• 作为产物：
  描述：

  9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 吡啶 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium cyanoborohydride 、 1-羟基苯并三唑 、 戴斯-马丁氧化剂 、 N,N-二异丙基乙胺 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 22.0h， 生成
  参考文献：
  名称：

  Large Molecular Assembly of Amphotericin B Formed in Ergosterol-Containing Membrane Evidenced by Solid-State NMR of Intramolecular Bridged Derivative

  摘要：

  Amphotericin B (AmB 1) is known to assemble and form an ion channel across biomembranes. We have recently reported that conformation-restricted derivatives of AmB 2-4 show different ergosterol preferences in ion-channel assays, which suggested that the orientation of the mycosamine strongly affects the sterol selectivity of AmB. The data allowed us to assume that compound 3 showing the highest selectivity would reflect the active conformation of AmB in the channel assembly. In this study, to gain further insight into the active conformation of AmB, we prepared a new intramolecular-bridged derivative 5, where the linker encompassed a hydrophilic glycine moiety. The derivative has almost equivalent ion-channel activity to those of AmB and 3. The antifungal activity of 5 compared with 3 improves significantly, possibly because the increasing hydrophilicity in the linker enhances the penetrability through the fungal cell wall. Conformation of 5 was well converged and very similar to that of 3, thus further supporting the notion that the conformations of these derivatives reproduce the active structure of AmB in the channel complex. Then we used the derivative to probe the mobility of AmB in the membrane by solid-state NMR. To measure dipolar couplings and chemical shift anisotropies, we incorporated [1-C-13, N-15] glycine into the linker. The results indicate that 5 is mostly immobilized in ergosterol-containing DMPC bilayers, implying formation of large aggregates of 5. Meanwhile some fraction of 5 remains mobile in sterol-free DMPC bilayers, suggesting promotion of AmB aggregation by ergosterol.

  DOI：

  10.1021/ja063433w