两性霉素B甲酯 | 36148-89-7

• 物质功能分类: 化学试剂 - 有机试剂 - 酯类
• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 两性霉素B甲酯
• 中文别名: 两性霉素B甲酯90
• 英文名称: amphotericin B methyl ester
• 英文别名: AME；methyl (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-amino-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-carboxylate
• CAS: 36148-89-7
• 化学式: C₄₈H₇₅NO₁₇
• 分子量: 938.12
• InChiKey: UAZIZEMIKKIBCA-TYVGYKFWSA-N

物化性质

• 熔点：
  >118°C (dec.)
• 沸点：
  1102.6±65.0 °C(Predicted)
• 密度：
  1.31±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于DMSO（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  66
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  309
• 氢给体数：
  11
• 氢受体数：
  18

制备方法与用途

生物活性

Amphotericin B methyl ester 是多烯类抗生素 Amphotericin B (A634250) 的甲酯衍生物。这种化合物是胆固醇的结合物，具有显著的抗真菌活性。此外，Amphotericin B methyl ester 还能够干扰 HIV-1 颗粒的产生，并抑制 HIV-1 的复制。

体外研究

Amphotericin B methyl ester 能有效抑制 HIV-1 病毒颗粒的生产，但对其 Gag 蛋白与质膜结合、Gag 与脂筏的关联以及 Gag 多聚化过程没有显著影响。

反应信息

• 作为反应物：
  描述：

  两性霉素B甲酯 在 lithium hydroxide 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 以80%的产率得到两性霉素B
  参考文献：
  名称：

  Total synthesis of amphotericin B

  摘要：

  DOI：

  10.1021/ja00243a043
• 作为产物：
  描述：

  两性霉素B 在 哌啶 、 吡啶 作用下， 反应 4.5h， 生成 两性霉素B甲酯
  参考文献：
  名称：

  Synthesis and biological evaluation of non-polyene analogs of amphotericin B

  摘要：

  Synthesis of the first analog of a polyene macrolide antibiotic containing a rigid, non-polyene backbone has been accomplished. The sterol recognition surface of amphotericin B has been modified in an effort to better understand the role of the polyene backbone. Its antifungal activity is reduced significantly compared with amphotericin B. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)10180-9

文献信息

• Amphotericin B methyl ester salts
  申请人：E. R. Squibb & Sons, Inc.

  公开号：US04041232A1

  公开（公告）日：1977-08-09

  Amphotericin B methyl ester salts, such as salts formed by reaction with mono and dicarboxylic amino acids (such as aspartic acid, or glutamic acid or pyroglutamic acid), hydroxy carboxylic acids (such as lactic acid) and mono and dicarboxylic acids (such as acetic acid) are provided and have been found to be readily water-soluble and at least as stable and active as the parent ester compound.

  提供了甲基酯盐的两性霉素B，例如与单和二羧基氨基酸（如天冬氨酸、谷氨酸或吡烯酰谷氨酸）、羟基羧酸（如乳酸）和单和二羧基酸（如乙酸）反应形成的盐，并发现它们容易水溶并且至少和母酯化合物一样稳定和活性。
• Polyene macrolide schiff bases, their alkyl esters and processes for
  申请人：Karykion Corporation

  公开号：US05981721A1

  公开（公告）日：1999-11-09

  Processes for the preparation of high purity alkyl esters of polyene macrolide antibiotics are disclosed. The processes involve treating an amphoteric polyene macrolide antibiotic with an aldehyde to yield the corresponding Schiff base which is soluble in the reaction medium. The solution is then treated with an alkylating agent in the presence of a hindered tertiary amine as acid acceptor to yield the alkyl ester of the polyene macrolide antibiotic in the form of its Schiff base derivative. Contacting this derivative with water converts the Schiff base derivative to the desired alkyl ester of the polyene macrolide antibiotic which is recovered from the reaction medium.

  本发明公开了制备高纯度多烯大环内酯抗生素烷基酯的方法。该方法涉及将两性多烯大环内酯抗生素与醛处理，以产生相应的席夫碱，其在反应介质中可溶。然后在有阻碍的三级胺作为酸受体的存在下，将该溶液与烷基化试剂处理，以产生多烯大环内酯抗生素的烷基酯，其以其席夫碱衍生物的形式存在。将该衍生物与水接触可将席夫碱衍生物转化为所需的多烯大环内酯抗生素烷基酯，该酯从反应介质中回收。
• Polyene macrolide derivative
  申请人：Shionogi & Co., Ltd.

  公开号：US10696707B2

  公开（公告）日：2020-06-30

  The present invention is the following Amphotericin B derivative: wherein each symbol is defined in description. The compound of the present invention has 16th position (X) is urea structure, cyclic structure, hydroxyalkyl or substituted monoalkylcarbamoyl. The compound of the present invention has antifungal activity.

  本发明是以下两性霉素 B 衍生物： 其中各符号在说明中定义。本发明化合物的第 16 位（X）是脲结构、环状结构、羟烷基或取代的单烷基氨基甲酰基。本发明化合物具有抗真菌活性。
• Amphotericin B covalent dimers with carbonyl-amino linkage: a new probe for investigating ion channel assemblies
  作者：Yuichi Umegawa、Nobuaki Matsumori、Tohru Oishi、Michio Murata

  DOI：10.1016/j.tetlet.2007.03.058

  日期：2007.5

  Based on an amphotericin B (AmB) ion-channel model where the close proximity of neighboring molecules is effected by interaction between carboxyl and amino groups, we prepared covalent dimers of AmB connected between these functionalities. While directly connected and short-tethered derivatives (2 and 3) lacked the activities, dimer 4 with a longer linker revealed K+ ion flux activity, suggesting that some distance and/or flexibility between the carboxyl and amino groups in adjacent molecules is required for the formation of ion-permeable complex in biomembranes. (c) 2007 Elsevier Ltd. All rights reserved.
• POLYENE MACROLIDE DERIVATIVE
  申请人：Shionogi & Co., Ltd.

  公开号：US20190135847A1

  公开（公告）日：2019-05-09

  The present invention is the following Amphotericin B derivative: wherein each symbol is defined in description. The compound of the present invention has 16th position (X) is urea structure, cyclic structure, hydroxyalkyl or substituted monoalkylcarbamoyl. The compound of the present invention has antifungal activity.