(1R,2S,3S,4S,5S,6RS,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-bis(methylene)-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.14,34.1^11,14.1^17,21.0^23,27] nonatriacontane-8,29-dione | 929121-23-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 呋喃吡喃类
• 英文名称: (1R,2S,3S,4S,5S,6RS,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-bis(methylene)-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.14,34.1^11,14.1^17,21.0^23,27] nonatriacontane-8,29-dione
• 英文别名: (2R,3R,3aS,7R,10S,11R,12S,13S,14S,15S,21S,24S,27S,29R,31R,32aS)-2-[(2S)-2,3-Dihydroxypropyl]octacosahydro-12,15-dihydroxy-3-methoxy-29-methyl-23,30-bis(methylene)-7,11:10,14:13,16:21,24:27,31-pentaepoxy-2H-cyclohentriaconta[b]furan-5,18(3H,6H)-dione；(1R,2S,3S,4S,5S,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-dimethylidene-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.13,6.14,34.111,14.117,21.023,27]nonatriacontane-8,29-dione
• CAS: 929121-23-3
• 化学式: C₄₀H₆₀O₁₃
• 分子量: 748.909
• InChiKey: DRIHUUFRFITXNV-CIOOILJMSA-N

物化性质

• 沸点：
  918.5±65.0 °C(Predicted)
• 密度：
  1.30±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  53
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  180
• 氢给体数：
  4
• 氢受体数：
  13

反应信息

• 作为反应物：
  描述：

  (1R,2S,3S,4S,5S,6RS,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-bis(methylene)-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.14,34.1^11,14.1^17,21.0^23,27] nonatriacontane-8,29-dione 在 吡啶 、 2,4,6-三甲基吡啶 、 ammonium hydroxide 、 4-甲基苯磺酸吡啶 作用下， 以 二氯甲烷 、 水 、 异丙醇 、 乙腈 为溶剂， 生成 甲磺酸艾日布林
  参考文献：
  名称：

  Commercial Manufacture of Halaven®: Chemoselective Transformations En Route to Structurally Complex Macrocyclic Ketones

  摘要：

  The evolution of the synthesis of Halaven (R) (E7389, INN eribulin mesylate) from a medicinal chemistry process to the execution of the final process on pilot scale is described. The completion of the synthesis of Halaven (R) from C1-C13 ester and C14-C35 sulfone alcohol involves a series of chemo-, regio-, and stereoselective transformations. Furthermore, a high-dilution macrocyclization presented a number of challenges for industrial-scale manufacture (throughput, processing time, and side reactions). This paper describes studies at Eisai leading to an understanding, optimization, and control of the chemistry that realized the reproducible commercial production of Halaven (R).

  DOI：

  10.1055/s-0032-1318026
• 作为产物：
  描述：

  ER-118046 在 四丁基氟化铵 、 咪唑盐酸盐 作用下， 反应 5.0h， 生成 (1R,2S,3S,4S,5S,6RS,11S,14S,17S,19R,21R,23S,25R,26R,27S,31R,34S)-25-[(2S)-2,3-dihydroxypropyl]-2,5-dihydroxy-26-methoxy-19-methyl-13,20-bis(methylene)-24,35,36,37,38,39-hexaoxaheptacyclo[29.3.1.1^3,6.14,34.1^11,14.1^17,21.0^23,27] nonatriacontane-8,29-dione
  参考文献：
  名称：

  [EN] PROCESS FOR THE PREPARATION OF ERIBULIN AND ITS INTERMEDIATES
  [FR] PROCÉDÉ DE PRÉPARATION D'ÉRIBULINE ET DE SES INTERMÉDIAIRES

  摘要：

  本发明涉及一种Eribulin中间体的制备方法。本发明采用成本较低的溶剂，而且工艺条件可以轻松地用于商业规模。

  公开号：

  WO2022101931A1

文献信息

• METHODS USEFUL IN THE SYNTHESIS OF HALICHONDRIN B ANALOGS
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US20150158881A1

  公开（公告）日：2015-06-11

  In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).

  总的来说，本发明涉及改进的方法，用于合成半龙脂素B的类似物，如厄立宾及其药用盐（例如，厄立宾甲磺酸盐）。
• Methods useful in the synthesis of halichondrin B analogs
  申请人：EISAI R&D MANAGEMENT CO., LTD.

  公开号：US10030032B2

  公开（公告）日：2018-07-24

  In general, the present invention features improved methods useful for the synthesis of analogs of halichondrin B, such as eribulin and pharmaceutically acceptable salts thereof (e.g., eribulin mesylate).

  总之，本发明的特点是改进了用于合成卤代菊酯 B 类似物的方法，如麦角林及其药学上可接受的盐（如麦角林甲磺酸盐）。
• US9303039B2
  申请人：——

  公开号：US9303039B2

  公开（公告）日：2016-04-05
• US9695188B2
  申请人：——

  公开号：US9695188B2

  公开（公告）日：2017-07-04