N-Acetyl Amphotericin B (~75%) | 902457-23-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯类和类似物
• 英文名称: N-Acetyl Amphotericin B (~75%)
• 英文别名: (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-acetamido-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxylic acid
• CAS: 902457-23-2
• 化学式: C₄₉H₇₅NO₁₈
• 分子量: 966.13
• InChiKey: DIGUUNRLVBJXKB-WUYRWYIMSA-N

物化性质

• 熔点：
  >140°C (dec.)
• 溶解度：
  DMSO（非常轻微），甲醇（非常轻微，加热）

计算性质

• 辛醇/水分配系数(LogP)：
  2.5
• 重原子数：
  68
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  323
• 氢给体数：
  12
• 氢受体数：
  18

反应信息

• 作为反应物：
  描述：

  1,6-己二胺 、 N-Acetyl Amphotericin B (~75%) 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 1-羟基苯并三唑 、 N,N-二异丙基乙胺 作用下， 以 二甲基亚砜 为溶剂， 反应 15.0h， 生成 (1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-acetamido-3,5-dihydroxy-6-methyloxan-2-yl]oxy-N-[6-[[(1R,3S,5R,6R,9R,11R,15S,16R,17R,18S,19E,21E,23E,25E,27E,29E,31E,33R,35S,36R,37S)-33-[(2R,3S,4S,5S,6R)-4-acetamido-3,5-dihydroxy-6-methyloxan-2-yl]oxy-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carbonyl]amino]hexyl]-1,3,5,6,9,11,17,37-octahydroxy-15,16,18-trimethyl-13-oxo-14,39-dioxabicyclo[33.3.1]nonatriaconta-19,21,23,25,27,29,31-heptaene-36-carboxamide
  参考文献：
  名称：

  Amphotericin B Dimers with Bisamide Linkage Bearing Powerful Membrane-Permeabilizing Activity

  摘要：

  [GRAPHIC]Covalently linked dimers of amphotericin B were prepared by cross-linking its carboxylic acid, Among these, a dimer with a linkage of 1,6-hexanediamine revealed potent hemolytic activity (EC50, 0.25 muM) while its N-acetyl derivative gave rise to large K+ ion flux in phosphatidylcholine liposomes, regardless of the presence or absence of sterols, suggesting that the dimers may serve as a tool for elucidating the structure of the ion channel assemblage formed by amphotericin B.

  DOI：

  10.1021/ol025982m
• 作为产物：
  描述：

  乙酸-N-琥珀酰亚胺酯 、 两性霉素B 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 0.5h， 生成 N-Acetyl Amphotericin B (~75%)
  参考文献：
  名称：

  Amphotericin B Dimers with Bisamide Linkage Bearing Powerful Membrane-Permeabilizing Activity

  摘要：

  [GRAPHIC]Covalently linked dimers of amphotericin B were prepared by cross-linking its carboxylic acid, Among these, a dimer with a linkage of 1,6-hexanediamine revealed potent hemolytic activity (EC50, 0.25 muM) while its N-acetyl derivative gave rise to large K+ ion flux in phosphatidylcholine liposomes, regardless of the presence or absence of sterols, suggesting that the dimers may serve as a tool for elucidating the structure of the ion channel assemblage formed by amphotericin B.

  DOI：

  10.1021/ol025982m

文献信息

• Retrosynthetic and synthetic chemistry on amphotericin B. Synthesis of C(1)–C(20) and C(21)–C(38) fragments and construction of the 38-membered macrocycle
  作者：K. C. Nicolaou、T. K. Chakraborty、R. A. Daines、N. S. Simpkins

  DOI：10.1039/c39860000413

  日期：——

  For the first time, amphotericin B (I) has been successfully derivatized and degraded to intermediates that have been converted into compounds (II)[C(1)–C(20) fragment] and (III)[C(21)–C(38) fragment], projected as major key intermediates for a total synthesis; methods have been developed for the coupling of fragments (II) and (III) to give the ketophosphonate–aldehyde (28) and for the cyclization

  首次将两性霉素B（I）成功衍生并降解为中间体，这些中间体已转化为化合物（II）[C（1）–C（20）片段]​​和（III）[C（21）–C （38）片段]，预计将作为总合成的主要关键中间体；已经开发出了一些方法来偶联片段（II）和（III），得到酮膦酸酯-醛（28），并将该前体环化成38元大环庚烯酮（29），产率为70-80％。