(1S,3R)-ethyl 1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate | 1453864-21-5

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 哈马拉生物碱
• 英文名称: (1S,3R)-ethyl 1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
• 英文别名: ethyl (1S,3R)-1-(3,4,5-trimethoxyphenyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1453864-21-5
• 化学式: C₂₃H₂₆N₂O₅
• 分子量: 410.47
• InChiKey: IGKVEIRSPYCJNV-XLIONFOSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  81.8
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  (1S,3R)-ethyl 2-(naphthalen-1-ylmethyl)-1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙腈 为溶剂， 60.0 ℃ 、111.46 kPa 条件下， 反应 8.0h， 以96%的产率得到(1S,3R)-ethyl 1-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydro-9H-pyrido[3,4-b]indole-3-carboxylate
  参考文献：
  名称：

  Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from l-tryptophan

  摘要：

  An efficient and general method for the highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs) into (15,3R)-trans-1,3-disubstituted THBCs is described. The method contains the following three steps: the enantiomerically pure (1S,3S)-cis-1,3-disubstituted THBCs 1 were first converted into (1S,3S)-cis-1,2,3-trisubstituted THBCs 2 by N-1-naphthylmethylation/benzylation; (15,3S)-cis-1,2,3-trisubstituted THBCs 2 were then converted into (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 in high yields and with high stereoselectivities via a base-catalyzed epimerization at C-3; (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 were subsequently converted into (15,3R)-trans-1,3-disubstituted THBCs 4 after reductive removal of the 1-naphthylmethyl/benzyl group. In addition, as an application of this method, an improved and highly stereoselective synthesis of the PDE5 inhibitor tadalafil (Cialis (R)) starting from natural and less expensive L-tryptophan was developed. (C) 2013 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2013.06.006

文献信息

• Highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted tetrahydro-β-carbolines into (1S,3R)-trans-1,3-disubstituted tetrahydro-β-carbolines: an improved asymmetric synthesis of tadalafil from l-tryptophan
  作者：Jing Dong、Tian-Zhuo Meng、Xiao-Xin Shi、Wen-Hui Zou、Xia Lu

  DOI：10.1016/j.tetasy.2013.06.006

  日期：2013.8

  An efficient and general method for the highly stereoselective transformation of (1S,3S)-cis-1,3-disubstituted 1,2,3,4-tetrahydro-beta-carbolines (THBCs) into (15,3R)-trans-1,3-disubstituted THBCs is described. The method contains the following three steps: the enantiomerically pure (1S,3S)-cis-1,3-disubstituted THBCs 1 were first converted into (1S,3S)-cis-1,2,3-trisubstituted THBCs 2 by N-1-naphthylmethylation/benzylation; (15,3S)-cis-1,2,3-trisubstituted THBCs 2 were then converted into (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 in high yields and with high stereoselectivities via a base-catalyzed epimerization at C-3; (1S,3R)-trans-1,2,3-trisubstituted THBCs 3 were subsequently converted into (15,3R)-trans-1,3-disubstituted THBCs 4 after reductive removal of the 1-naphthylmethyl/benzyl group. In addition, as an application of this method, an improved and highly stereoselective synthesis of the PDE5 inhibitor tadalafil (Cialis (R)) starting from natural and less expensive L-tryptophan was developed. (C) 2013 Elsevier Ltd. All rights reserved.