33-(tert-butyldimethylsilyl)-24-deoxy-ascomycin | 134226-79-2

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酯内酰胺
• 英文名称: 33-(tert-butyldimethylsilyl)-24-deoxy-ascomycin
• 英文别名: (1R,9S,12S,13R,17R,18E,21S,23S,24R,25S,27R)-17-ethyl-1-hydroxy-12-[(E)-1-[(1R,3R,4R)-4-hydroxy-3-methoxycyclohexyl]prop-1-en-2-yl]-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-azatricyclo[22.3.1.04,9]octacos-18-ene-2,3,10,16-tetrone
• CAS: 134226-79-2
• 化学式: C₄₃H₆₉NO₁₁
• 分子量: 776.021
• InChiKey: IGZKWIHLQSVVDX-NCAZQSQBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  55
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.81
• 拓扑面积：
  158
• 氢给体数：
  2
• 氢受体数：
  11

反应信息

• 作为反应物：
  描述：

  33-(tert-butyldimethylsilyl)-24-deoxy-ascomycin 在 4-二甲氨基吡啶 、 sodium azide 、 三乙胺 、 三苯基膦 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 (E)-(1R,9S,12S,13R,17R,21S,23S,24R,25S,27R)-12-[(E)-2-((1R,3R,4S)-4-Amino-3-methoxy-cyclohexyl)-1-methyl-vinyl]-17-ethyl-1-hydroxy-23,25-dimethoxy-13,19,21,27-tetramethyl-11,28-dioxa-4-aza-tricyclo[22.3.1.0^4,9]octacos-18-ene-2,3,10,16-tetraone
  参考文献：
  名称：

  C32-amino derivatives of the immunosuppressant ascomycin

  摘要：

  Various C32-amino derivatives were investigated as replacements for the C32-hydroxyl group of ascomycin and its C24-deoxy analog. The syntheses of these amino derivatives and their biological evaluation are reported herein. (C) 1997 Elsevier Science Ltd.

  DOI：

  10.1016/s0960-894x(97)00409-5
• 作为产物：
  描述：

  长川霉素 在 palladium 10% on activated carbon 、 氢气 、 对甲苯磺酸 作用下， 以 甲醇 、 甲苯 为溶剂， 反应 1.3h， 生成 33-(tert-butyldimethylsilyl)-24-deoxy-ascomycin
  参考文献：
  名称：

  [EN] ANTIFUNGAL COMPOUNDS
  [FR] COMPOSÉS ANTIFONGIQUES

  摘要：

  该发明涉及制药化合物、组合物和方法的技术领域。在一个方面，该公开提供了大环内酯化合物和与第二活性剂的组合，适用于用作抗真菌疗法，以及其使用方法和含有相同化合物的组合物。大环内酯化合物包括FK506的环异构体和相关类似物。

  公开号：

  WO2015106283A1

文献信息

• Regioselective Carbon–Carbon Bond Formation in the Effector Domain of Ascomycin
  作者：Amarylla Horvath、Maximilian A Grassberger、Gerhard Schulz、Ewald Haidl、Hildegard Sperner、Andrea Steck

  DOI：10.1016/s0040-4020(00)00669-4

  日期：2000.9

  Starting from 33-O-silyl-protected ascomycin or its 23,24-dehydration product, regio- and stereo-selective formal aldol reactions under carbon–carbon bond formation at C-22, C-23, or C-24 are demonstrated. Additionally, with the 22-silyl enol ether ascomycin derivative a rhodium(I)-catalysed shift of the 19,20 double bond into the 19,38 exocyclic position is observed at elevated temperature.

  从33 - O-甲硅烷基保护的子囊霉素或其23,24-脱水产物开始，证明了在C-22，C-23或C-24处碳-碳键形成下的区域和立体选择性形式的羟醛反应。另外，使用22-甲硅烷基烯醇醚子囊霉素衍生物，在升高的温度下观察到了铑（I）催化的19,20双键向19,38环外位置的移位。
• Antifungal compounds
  申请人：Duke University

  公开号：US10568872B2

  公开（公告）日：2020-02-25

  The technical field of the invention is in pharmaceutical compounds and methods. In an aspect, the disclosure provides macrolide compounds suitable for use as antifungal agents, as well as methods for their use and compositions containing the same.

  本发明的技术领域是药物化合物和方法。在一个方面，本发明提供了适合用作抗真菌剂的大环内酯类化合物，以及它们的使用方法和含有这些化合物的组合物。
• Retention of Immunosuppressant Activity in an Ascomycin Analogue Lacking a Hydrogen-Bonding Interaction with FKBP12
  作者：Paul E. Wiedeman、Stephen W. Fesik、Andrew M. Petros、David G. Nettesheim、Karl W. Mollison、Benjamin C. Lane、Yat Sun Or、Jay R. Luly

  DOI：10.1021/jm980252z

  日期：1999.10.1

  C24-Deoxyascomycin was prepared in a two-step process from ascomycin and evaluated for its immunosuppressant activity relative to ascomycin and FK506. An intermediate in the synthetic pathway, Delta(23,24)-dehydroascomycin, was likewise evaluated. Despite lacking the hydrogen-bonding interactions associated with the C24-hydroxyl moiety of ascomycin, C24-deoxyascomycin was found to be equipotent to the parent compound both in its immunosuppressive potency and in its interaction with the immunophilin, FKBP12. Conversely, Delta(23,24)-dehydroascomycin which also lacks the same hydrogen-bonding interactions did not exhibit this potency. NMR studies were conducted on the FKBP12/C24-deoxyascomycin complex in an attempt to understand this phenomenon at the molecular level. The NMR structures of the complexes formed between FKBP12 and ascomcyin or C24-deoxyascomcyin were very similar, suggesting that hydrogen-bonding interactions with the C24 hydroxyl moiety are not important; for complex formation.
• Antifungal Compounds
  申请人：Amplyx Pharmaceuticals, Inc.

  公开号：US20160331730A1

  公开（公告）日：2016-11-17

  The technical field of the invention is in pharmaceutical compounds and methods. In an aspect, the disclosure provides macrolide compounds suitable for use as antifungal agents, as well as methods for their use and compositions containing the same.
• ANTIFUNGAL COMPOUNDS
  申请人：Duke University

  公开号：US20200188364A1

  公开（公告）日：2020-06-18

  The technical field of the invention is in pharmaceutical compounds and methods. In an aspect, the disclosure provides macrolide compounds suitable for use as antifungal agents, as well as methods for their use and compositions containing the same.