2,6-Bis-[(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-hexanoic acid | 824393-83-1

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 类固醇和类固醇衍生物
• 英文名称: 2,6-Bis-[(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-hexanoic acid
• 英文别名: 2,6-bis[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]hexanoic acid
• CAS: 824393-83-1
• 化学式: C₅₄H₉₀N₂O₁₀
• 分子量: 927.316
• InChiKey: IXQWQEUBYPLYKR-LUNOCBQZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.1
• 重原子数：
  66
• 可旋转键数：
  15
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.94
• 拓扑面积：
  217
• 氢给体数：
  9
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  四亚甲基二胺 、 2,6-Bis-[(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-hexanoic acid 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 生成 N-[4-[2,6-bis[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]hexanoylamino]butyl]-2,6-bis[[(4R)-4-[(3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-2,3,4,5,6,7,8,9,11,12,14,15,16,17-tetradecahydro-1H-cyclopenta[a]phenanthren-17-yl]pentanoyl]amino]hexanamide
  参考文献：
  名称：

  过硫酸化分子伞作为抗 HIV 和抗 HSV 药物

  摘要：

  已经从腐胺、亚精胺、精胺、赖氨酸和胆酸（1a、2a、3a、4a 和 5a）合成了一系列过硫酸化分子伞，并确定了它们的抗 HIV 和抗 HSV 活性。尽管大小，这些缀合物中最活跃的 (5a) 能够穿过由 1-棕榈酰-2-油酰-sn-甘油-3-磷酸胆碱 (POPC) 和 1-棕榈酰-2-油酰-sn-制成的磷脂双层甘油-3-磷脂酰甘油 (POPG)。抗病毒活性、跨越疏水屏障的能力、缺乏细胞毒性以及从生物起始材料的简单三步合成的独特组合表明 5a 和相关缀合物可用作一类新型抗病毒剂用于全身和局部应用。

  DOI：

  10.1021/ja044400o
• 作为产物：
  描述：

  胆酸 在 三乙胺 、 N,N'-二环己基碳二亚胺 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 生成 2,6-Bis-[(R)-4-((3R,5S,7R,8R,9S,10S,12S,13R,14S,17R)-3,7,12-trihydroxy-10,13-dimethyl-hexadecahydro-cyclopenta[a]phenanthren-17-yl)-pentanoylamino]-hexanoic acid
  参考文献：
  名称：

  Molecular Umbrella-Assisted Transport of an Oligonucleotide across Cholesterol-Rich Phospholipid Bilayers

  摘要：

  A series of molecular umbrella conjugates, derived from cholic acid, deoxycholic acid, spermidine, lysine, and 5-mercapto-2-nitrobenzoic acid, have been synthesized and found capable of transporting an attached 16-mer oligonucleotide (S-dT(16)) across liposomal membranes made from 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC), 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphatidyldglycerol (POPG), and cholesterol [POPC/POPG/cholesterol (65/5/30; mol/mol/mol, v/v/v)] at 37 degrees C. Those molecular umbrellas containing four choloyl (or deoxycholoyl) groups resulted in significantly faster rates of transport as compared to those containing only two such moieties. A model that accounts for these membrane transport processes is proposed.

  DOI：

  10.1021/ja053930x

文献信息

• Taming Amphotericin B
  作者：Vaclav Janout、Wiley A. Schell、Damien Thévenin、Yuming Yu、John R. Perfect、Steven L. Regen

  DOI：10.1021/acs.bioconjchem.5b00463

  日期：2015.10.21

  A strategy is introduced for enhancing the cellular selectivity of Amphotericin B (AmB) and other classes of membrane-disrupting agents. This strategy involves attaching the agent to a molecular umbrella to minimize the disruptive power of aggregated forms. Based on this approach, AmB has been coupled to a molecular umbrella derived from one spermidine and two cholic acid molecules and found to have antifungal activities approaching that of the native drug. However, in sharp contrast to AmB, the hemolytic activity and the cytotoxcity of this conjugate toward HEK293 T cells have been dramatically reduced.

  引入了一种增强两性霉素 B (AmB) 和其他类型的膜破坏剂的细胞选择性的策略。该策略涉及将药剂附着在分子伞上，以最大限度地减少聚集形式的破坏力。基于这种方法，AmB 与由一个亚精胺和两个胆酸分子衍生的分子伞偶联，并发现其具有接近天然药物的抗真菌活性。然而，与 AmB 形成鲜明对比的是，该缀合物对 HEK293 T 细胞的溶血活性和细胞毒性已显着降低。