(1R,6S,8aR)-6-(N,N-dibenzylamino)-1-octahydroindolizinol | 159498-00-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚里西啶
• 英文名称: (1R,6S,8aR)-6-(N,N-dibenzylamino)-1-octahydroindolizinol
• 英文别名: (1R,6S,8aR)-6-(dibenzylamino)-1,2,3,5,6,7,8,8a-octahydroindolizin-1-ol
• CAS: 159498-00-7
• 化学式: C₂₂H₂₈N₂O
• 分子量: 336.477
• InChiKey: JXXIYVYDDPXBIP-BHDDXSALSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  26.7
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (1R,6S,8aR)-6-(N,N-dibenzylamino)-1-octahydroindolizinol 在 palladium dihydroxide 氢气 作用下， 以 四氢呋喃 、 甲醇 为溶剂， 反应 170.0h， 生成 (-)-1,8a-Diepislaframine
  参考文献：
  名称：

  Enantiomerically Pure Amino Alcohols and Diamino Alcohols from L-Aspartic Acid. Application to the Synthesis of Epi- and Diepislaframine

  摘要：

  Starting from natural aspartic acid (6) a practical method for the synthesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diamino derivatives is described. After perbenzylation of 6 and reduction of both carboxylates, position 4 of the resultant (dibenzylamino)butanediol (11) could be regioselectively blocked to afford the silyloxy-protected intermediate 12a. Functionalization of position 1 was accomplished by nucleophilic displacement reactions including a 2-fold migration of the dibenzylamino substituent or by reductive amination of the amino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, report on the application of this method to a chirospecific synthesis of epi- and diepislaframine (9a and 9b) as diastereomers of the highly bioactive indolizidine alkaloid slaframine (9c). Our first approach including reductive coupling of the chiral amino aldehyde 15 with 5-hydroxypyrrolidine failed when formation of a quaternary ammonium salt occurred, preventing the anticipated anionic cyclization. Therefore, we turned out attention to methodology developed by Wasserman. In fact, introduction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi- and diepislaframine.

  DOI：

  10.1021/jo00101a042
• 作为产物：
  描述：

  tert-butyl (6S)-6-(N,N-dibenzylamino)-2,3,5,6,7,8-hexahydro-1-oxo-8a(1H)-indolizinecarboxylate 在 sodium tetrahydroborate 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 (1R,6S,8aR)-6-(N,N-dibenzylamino)-1-octahydroindolizinol
  参考文献：
  名称：

  Enantiomerically Pure Amino Alcohols and Diamino Alcohols from L-Aspartic Acid. Application to the Synthesis of Epi- and Diepislaframine

  摘要：

  Starting from natural aspartic acid (6) a practical method for the synthesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diamino derivatives is described. After perbenzylation of 6 and reduction of both carboxylates, position 4 of the resultant (dibenzylamino)butanediol (11) could be regioselectively blocked to afford the silyloxy-protected intermediate 12a. Functionalization of position 1 was accomplished by nucleophilic displacement reactions including a 2-fold migration of the dibenzylamino substituent or by reductive amination of the amino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, report on the application of this method to a chirospecific synthesis of epi- and diepislaframine (9a and 9b) as diastereomers of the highly bioactive indolizidine alkaloid slaframine (9c). Our first approach including reductive coupling of the chiral amino aldehyde 15 with 5-hydroxypyrrolidine failed when formation of a quaternary ammonium salt occurred, preventing the anticipated anionic cyclization. Therefore, we turned out attention to methodology developed by Wasserman. In fact, introduction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi- and diepislaframine.

  DOI：

  10.1021/jo00101a042

文献信息

• Enantiomerically Pure Amino Alcohols and Diamino Alcohols from L-Aspartic Acid. Application to the Synthesis of Epi- and Diepislaframine
  作者：Peter Gmeiner、Dagmar Junge、Annerose Kaertner

  DOI：10.1021/jo00101a042

  日期：1994.11

  Starting from natural aspartic acid (6) a practical method for the synthesis of enantiomerically pure 3-amino alcohols 8 including 3,4-diamino derivatives is described. After perbenzylation of 6 and reduction of both carboxylates, position 4 of the resultant (dibenzylamino)butanediol (11) could be regioselectively blocked to afford the silyloxy-protected intermediate 12a. Functionalization of position 1 was accomplished by nucleophilic displacement reactions including a 2-fold migration of the dibenzylamino substituent or by reductive amination of the amino aldehyde 15. Both routes proceeded under complete preservation of the optical purity. For envisioned SAR studies, we, furthermore, report on the application of this method to a chirospecific synthesis of epi- and diepislaframine (9a and 9b) as diastereomers of the highly bioactive indolizidine alkaloid slaframine (9c). Our first approach including reductive coupling of the chiral amino aldehyde 15 with 5-hydroxypyrrolidine failed when formation of a quaternary ammonium salt occurred, preventing the anticipated anionic cyclization. Therefore, we turned out attention to methodology developed by Wasserman. In fact, introduction of a 3-hydroxypyrrole-2-carboxylate fragment gave a cyclization precursor (30b) which could be successfully transformed into epi- and diepislaframine.