(1S,3R)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride | 1609374-53-9

• 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)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride
• 英文别名: Tadalafil-016-1S3R-HCl；methyl (1S,3R)-1-(1,3-benzodioxol-5-yl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate;hydrochloride
• CAS: 1609374-53-9
• 化学式: C₂₀H₁₈N₂O₄*ClH
• 分子量: 386.835
• InChiKey: ROYJOKDTCKPQHK-CFILVAQYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  27.0
• 可旋转键数：
  2.0
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  72.58
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  (1S,3R)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride 生成 methyl (1R,3R)-1-(3,4-methylenedioxyphenyl)-2-chloroacetyl-2,3,4,9-tetrahydro-9H-pyrido[3,4-b]indol-3-carboxylate
  参考文献：
  名称：

  Tetrahedron: Asymmetry 2009, 20, 2090-2096

  摘要：

  DOI：
• 作为产物：
  描述：

  (S)-1-benzo[1,3]dioxol-5-yl-2-benzyl-2,3,4,9-tetrahydro-1H-β-carboline-(R)-3-carboxylic acid methyl ester 在 盐酸 、 palladium 10% on activated carbon 、 氢气 作用下， 以 水 、 乙腈 为溶剂， 60.0 ℃ 、111.47 kPa 条件下， 反应 8.0h， 生成 (1S,3R)-1-(3,4-methylenedioxyphenyl)-1,2,3,4-tetrahydro-pyrido[3,4-b]indole-3-carboxylic acid methyl ester hydrochloride
  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 Pictet–Spengler reaction of d-tryptophan methyl ester with piperonal: convenient syntheses of Cialis (Tadalafil), 12a-epi-Cialis, and their deuterated analogues
  作者：Xiao-Xin Shi、Shi-Ling Liu、Wei Xu、Yu-Lan Xu

  DOI：10.1016/j.tetasy.2007.12.017

  日期：2008.3

  The acid-catalyzed Pictet-Spengler reaction Of D-tryptophan methyl ester with piperonal in acetic acid has been reported, the best stereo selectivity (cis/trans = 92:8) was obtained with benzoic acid as the catalyst. The Pictet-Spengler reaction Of D-tryptophan methyl ester hydrochloride with piperonal in various solvents has been extensively studied, the solvent-dependence of stereoselectivities could be principally attributed to the solubility-difference between cis and trans products 5-HCl in the used solvent, the best stereoselectivity (cis/trans = 99: 1) was obtained using nitromethane or acetonitrile as the solvent. A base-catalyzed epimerization at 12a-position of Cialis 1 (tadalafil) in a DMSO-containing solvent was also exploited. Cialis, 12a-epi-Cialis 2, deuterium-labeled 3,3,12a-d(3)-Cialis 3, and 3,3,12a-d(3)-12a-epi-Cialis 4 were efficiently synthesized from D-tryptophan methyl ester hydrochloride. (C) 2008 Elsevier Ltd. All rights reserved.
• Tetrahedron: Asymmetry 2013, 24, 883-893
  作者：

  DOI：——

  日期：——