(1R,12bS)-1-(2',2'-diethoxycarbonylethyl)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine | 1007570-56-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: (1R,12bS)-1-(2',2'-diethoxycarbonylethyl)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine
• 英文别名: 2-(((1R,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinazine-1-yl)methyl)diethyl malonate；diethyl 2-[[(1R,12bS)-1-ethyl-3,4,6,7,12,12b-hexahydro-2H-indolo[2,3-a]quinolizin-1-yl]methyl]propanedioate
• CAS: 1007570-56-0
• 化学式: C₂₅H₃₄N₂O₄
• 分子量: 426.556
• InChiKey: SFKUSVLDCATJHU-RCZVLFRGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  9
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  71.6
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (1R,12bS)-1-(2',2'-diethoxycarbonylethyl)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine 在 氢氧化钾 、 溶剂黄146 、 sodium nitrite 作用下， 以 乙醇 为溶剂， 反应 4.0h， 生成 ethyl (1R,12bS)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a]quinolizine-1-(2'-hydroxyimino)propionate
  参考文献：
  名称：

  Synthesis and Evaluation of 2′-Hydroxyethyl trans-Apovincaminate Derivatives as Antioxidant and Cognitive Enhancer Agents

  摘要：

  A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b-f and 7b-f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a,b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3R,16S)-2'-hydroxyethyl apovincaminate (7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.

  DOI：

  10.1021/jm070618k
• 作为产物：
  描述：

  diethyl 15aR-ethyl-2,3,6,11,15,15a-hexahydro-1H,5H-indolo[2,3-a]pyrano[3,2-i]quinolizine-14,14-(13H)-dicarboxylate 在 溶剂黄146 、 sodium tetrahydroborate 、 氨 作用下， 以 乙醇 为溶剂， 反应 1.34h， 以61%的产率得到(1R,12bS)-1-(2',2'-diethoxycarbonylethyl)-1-ethyl-1,2,3,4,6,7,12,12b-octahydroindolo[2,3-a] quinolizine
  参考文献：
  名称：

  长春胺手性杂质的制备方法

  摘要：

  本发明涉及长春胺手性杂质的制备方法。本发明通过定向合成的方法，以及后期的柱层析分离，从而得到了七个手性杂质的高纯品，并将其用于长春胺生产中的杂质定性和定量的分析，实现了长春胺药物中七个手性杂质分离确认，并提高了长春胺的药品质量标准，从而能够获得高纯度的长春胺。与现有的长春胺的制备方法相比，本发明涉及到了七个手性异构体的制备，制备方法更加的全面，且操作简单。

  公开号：

  CN109384781B

文献信息

• Synthesis of vinca alkaloids and related compounds—XVI
  作者：Lajos Szabó、János Sápi、György Kalaus、Gyula Argay、Alajos Kálmán、Eszter Baitz-Gács、József Tamás、Csaba Szántay

  DOI：10.1016/s0040-4020(01)88614-2

  日期：1983.1

  A stereoselective method has been elaborated for the synthesis of oxime esters, (-)-4a, b, from which, as common intermediates, (+)-apovincaminic acid esters (3a,b), (+)-vincamine (1) and (-)-vincamone (2) can be prepared.

  为合成肟酯（-）- 4a和b，已拟定了一种立体选择方法，从该酯中，作为常见中间体，可以合成（+）-apovincaminic酸酯（3a，b），（+）-长春胺（1）和可以制备（-）-长春蔓酮（2）。
• Synthesis and Evaluation of 2′-Hydroxyethyl <i>trans-</i>Apovincaminate Derivatives as Antioxidant and Cognitive Enhancer Agents
  作者：András Nemes、László Czibula、Csaba Szántay, Jr.、Anikó Gere、Béla Kiss、Judit Laszy、István Gyertyán、Zsolt Szombathelyi、Csaba Szántay

  DOI：10.1021/jm070618k

  日期：2008.2.1

  A series of trans-2'-hydroxyethyl and 2'-acyloxyethyl apovincaminates 4b-f and 7b-f has been synthesized and evaluated for their antioxidant and antiamnesic effects. The new esters were prepared from 4a and 7a ethyl esters or from the corresponding carboxylic acid sodium salt. For starting materials 11a,b, a new stereoselective trans-reduction was elaborated. From the combined results of the data obtained from in vitro and in vivo tests and examination of the metabolism, (3R,16S)-2'-hydroxyethyl apovincaminate (7b, RGH-10885) was identified as the most promising compound, owing to its potent neuroprotective and antiamnesic activities. The in vivo effectiveness of selected compounds on the cognitive functions was studied in a one-trial passive avoidance task and a water-labyrinth test.
• 长春胺手性杂质的制备方法
  申请人：北京康派森医药科技有限公司

  公开号：CN109384781B

  公开（公告）日：2020-07-07

  本发明涉及长春胺手性杂质的制备方法。本发明通过定向合成的方法，以及后期的柱层析分离，从而得到了七个手性杂质的高纯品，并将其用于长春胺生产中的杂质定性和定量的分析，实现了长春胺药物中七个手性杂质分离确认，并提高了长春胺的药品质量标准，从而能够获得高纯度的长春胺。与现有的长春胺的制备方法相比，本发明涉及到了七个手性异构体的制备，制备方法更加的全面，且操作简单。