trans-1-phenyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acid ethyl ester | 1227610-59-4

• 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: trans-1-phenyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acid ethyl ester
• 英文别名: trans-ethyl 1-phenyl-2,3,4,9-tetrahydro-1H-β-carboline-3-carboxylate；ethyl (1R,3S)-1-phenyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole-3-carboxylate
• CAS: 1227610-59-4
• 化学式: C₂₀H₂₀N₂O₂
• 分子量: 320.391
• InChiKey: UTVKLYNVIXITRK-ZWKOTPCHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  54.1
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  trans-1-phenyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acid ethyl ester 在 potassium carbonate 作用下， 以 乙醇 为溶剂， 反应 48.0h， 生成 trans-2-benzyl-6-phenyl-3,4,6,7,12,12a-hexahydro-2H-pyrazino[1',2':1,6]pyrido[3,4-b]indol-1-one
  参考文献：
  名称：

  Synthesis of Functionalized Diketopiperazines as Cyclotryprostatin and Tryprostatin Analogues

  摘要：

  Various ketopiperazines were synthesized as (cyclo) tryprostatin analogues. Construction of the skeleton started with a Pictet-Spengler reaction followed by acylation or alkylation of the piperidine nitrogen and condensation with a primary amine. 2-Chloroacetyl tetrahydro-beta-carbolines rearranged towards the corresponding 2-chloro-N-[2-(1H-indol-3-yl)ethyl]acetamide derivatives upon treatment with NBS. These compounds were cyclized with primary amines towards the corresponding functionalized diketopiperazines.

  DOI：

  10.1055/s-0032-1316911
• 作为产物：
  描述：

  L-色氨酸乙酯盐酸盐 、 苯甲醛 在 三氟乙酸 作用下， 以 苯 为溶剂， 生成 trans-1-phenyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acid ethyl ester 、 cis-1-phenyl-1,2,3,4-tetrahydro-9H-β-carboline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  三取代1,2,3,4-四氢-β-咔啉顺反式差向异构化机理研究

  摘要：

  众所周知，Nb-苄基色氨酸烷基酯与醛发生Pictet-Spengler反应，生成顺式和反式-1,2,3,4-四氢-β-咔啉，其中反式异构体占主导地位。C-1 处的差向异构化在酸性条件下发生，通过内部不对称诱导专门产生热力学上更稳定的反式非对映异构体。最近的动力学实验深入了解了1,2,3-三取代四氢-β-咔啉的 Pictet−Spengler 反应中涉及的顺式到反式差向异构化机制。由于差向异构反应已被证明对 C-1 处的电子效应敏感，因此通过 Hammett 研究研究了一系列 1-苯基取代的 1,2,3,4-四氢-β-咔啉的速率数据。数据分析支持ρ值为-1.4的带正电中间体的存在，尽管仅从该数据无法确定亚胺离子中间体或碳阳离子中间体的存在。对差向异构化速率的分析证明了底物初始质子化后 TFA 的一级动力学。这一观察结果与双质子化中间体的形成一致，该中间体是碳阳离子介导的顺式到反式差向异构化过

  DOI：

  10.1021/jo1003778

文献信息

• The Discovery of Tadalafil:  A Novel and Highly Selective PDE5 Inhibitor. 1: 5,6,11,11a-Tetrahydro-1<i>H</i>-imidazo[1‘,5‘:1,6]pyrido[3,4-<i>b</i>]indole-1,3(2<i>H</i>)-dione Analogues
  作者：Alain Daugan、Pascal Grondin、Cécile Ruault、Anne-Charlotte Le Monnier de Gouville、Hervé Coste、Jorge Kirilovsky、François Hyafil、Richard Labaudinière

  DOI：10.1021/jm030056e

  日期：2003.10.1

  Starting from ethyl beta-carboline-3-carboxylate (beta-CCE), 1, a modest inhibitor of type 5 phosphodiesterase (PDE5), a series of functionalized tetrahydro-p-carboline derivatives has been identified as a novel chemical class of potent and selective PDE5 inhibitors. Optimization of the side chain on the hydantoin ring of initial lead compound 2 and of the aromatic ring on position 5 led to the identification of compound 6e, a highly potent and selective PDE5 inhibitor, with greater selectivity for PDE5 vs PDE1-4 than sildenafil. Compound 6e demonstrated a long-lasting and significant blood pressure lowering effect after iv administration in the spontaneously hypertensive rat model but showed only moderate oral in vivo efficacy.
• Mechanistic Studies on the <i>Cis</i> to <i>Trans</i> Epimerization of Trisubstituted 1,2,3,4-Tetrahydro-β-carbolines
  作者：Michael L. Van Linn、James M. Cook

  DOI：10.1021/jo1003778

  日期：2010.6.4

  reaction with aldehydes to furnish both cis- and trans-1,2,3,4-tetrahydro-β-carbolines, with the trans isomer predominating. Epimerization at C-1 took place under acidic conditions to produce, exclusively, the thermodynamically more stable trans diastereomer via internal asymmetric induction. Recent kinetic experiments provided insight into the cis to trans epimerization mechanism involved in the Pictet−Spengler

  众所周知，Nb-苄基色氨酸烷基酯与醛发生Pictet-Spengler反应，生成顺式和反式-1,2,3,4-四氢-β-咔啉，其中反式异构体占主导地位。C-1 处的差向异构化在酸性条件下发生，通过内部不对称诱导专门产生热力学上更稳定的反式非对映异构体。最近的动力学实验深入了解了1,2,3-三取代四氢-β-咔啉的 Pictet−Spengler 反应中涉及的顺式到反式差向异构化机制。由于差向异构反应已被证明对 C-1 处的电子效应敏感，因此通过 Hammett 研究研究了一系列 1-苯基取代的 1,2,3,4-四氢-β-咔啉的速率数据。数据分析支持ρ值为-1.4的带正电中间体的存在，尽管仅从该数据无法确定亚胺离子中间体或碳阳离子中间体的存在。对差向异构化速率的分析证明了底物初始质子化后 TFA 的一级动力学。这一观察结果与双质子化中间体的形成一致，该中间体是碳阳离子介导的顺式到反式差向异构化过
• Synthesis of Functionalized Diketopiperazines as Cyclotryprostatin and Tryprostatin Analogues
  作者：Norbert De Kimpe、Tuyen Nguyen Van、Pieter Claes

  DOI：10.1055/s-0032-1316911

  日期：——

  Various ketopiperazines were synthesized as (cyclo) tryprostatin analogues. Construction of the skeleton started with a Pictet-Spengler reaction followed by acylation or alkylation of the piperidine nitrogen and condensation with a primary amine. 2-Chloroacetyl tetrahydro-beta-carbolines rearranged towards the corresponding 2-chloro-N-[2-(1H-indol-3-yl)ethyl]acetamide derivatives upon treatment with NBS. These compounds were cyclized with primary amines towards the corresponding functionalized diketopiperazines.