1-propyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole

• 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: 1-propyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• 英文别名: (1~{S})-1-propyl-2,3,4,9-tetrahydro-1~{H}-pyrido[3,4-b]indole；(1S)-1-propyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• 化学式: C₁₄H₁₈N₂
• 分子量: 214.31
• InChiKey: BBOAWHADGQBLBD-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  16
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  27.8
• 氢给体数：
  2
• 氢受体数：
  1

反应信息

• 作为产物：
  描述：

  色胺盐酸盐 在 ammonia borane 、 sodium hydroxide 作用下， 以 aq. phosphate buffer 为溶剂， 37.0 ℃ 、101.33 kPa 条件下， 反应 48.0h， 生成 1-propyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
  参考文献：
  名称：

  Monoamine Oxidase (MAO-N) Catalyzed Deracemization of Tetrahydro-β-carbolines: Substrate Dependent Switch in Enantioselectivity

  摘要：

  The tetrahydro-beta-carboline (THBC) ring system is an important structural motif found in a large number of bioactive alkaloid natural products. Herein we report a broadly applicable method for the synthesis of enantiomerically pure beta-carbolines via a deracemization procedure employing the D9 and D11 variants of monoamine oxidase from Aspergillus niger (MAO-N) in combination with a nonselective chemical reducing agent. Biotransformations were performed on a preparative scale, leading to the synthesis of optically enriched products in excellent enantiomeric excess (e.e.; up to 99%) and isolated yield (up to 93%). Interestingly, a switch in enantioselectivity associated with the MAO-N variants is observed as the nature of the C-1 substituent of the THBC is varied. Molecular modeling provided an explanation for this observation and highlighted key active site residues which were modified, resulting in an increase in (R)-selectivity associated with the enzyme. These results provide insight into the factors which influence the selectivity of the MAO-N variants, and may offer a platform for future directed evolution projects aimed toward the challenge of engineering (R)-selective amine oxidase biocatalysts.

  DOI：

  10.1021/cs400724g

文献信息

• Development of an<i>R</i>-Selective Amine Oxidase with Broad Substrate Specificity and High Enantioselectivity
  作者：Rachel S. Heath、Marta Pontini、Beatrice Bechi、Nicholas J. Turner

  DOI：10.1002/cctc.201301008

  日期：2014.4

  Amine oxidases are useful bio‐catalysts for the synthesis of enantiomerically pure 1°, 2° and 3° chiral amines. Enzymes in this class (e.g., MAO‐N from Aspergillus niger) reported previously have been shown to be highly S selective. Herein we report the development of an enantiocomplementary R‐selective amine oxidase based on 6‐hydroxy‐D‐nicotine oxidase (6‐HDNO) with broadened substrate scope and

  胺氧化酶是用于合成对映体纯的1°，2°和3°手性胺的有用生物催化剂。先前报道的此类酶（例如，来自黑曲霉的MAO-N ）已显示出高度的S选择性。在此，我们报道了基于6-羟基-D-烟碱氧化酶（6-HDNO）的对映体互补R-选择性胺氧化酶的开发，该酶具有扩大的底物范围和高对映选择性。工程化的6-HDNO酶已应用于一系列外消旋胺的制备脱硝反应，以产生具有S构型的产物，例如高ee的（S）-烟碱。
• Asymmetric Synthesis of ( <i>R</i> )‐1‐Alkyl‐Substituted Tetrahydro‐ß‐carbolines Catalyzed by Strictosidine Synthases
  作者：Desiree Pressnitz、Eva‐Maria Fischereder、Jakob Pletz、Christina Kofler、Lucas Hammerer、Katharina Hiebler、Horst Lechner、Nina Richter、Elisabeth Eger、Wolfgang Kroutil

  DOI：10.1002/anie.201803372

  日期：2018.8.13

  Stereoselective methods for the synthesis of tetrahydro-ß-carbolines are of significant interest due to the broad spectrum of biological activity of the target molecules. In the plant kingdom, strictosidine synthases catalyze the C-C coupling through a Pictet-Spengler reaction of tryptamine and secologanin to exclusively form the (S)-configured tetrahydro-ß-carboline (S)-strictosidine. Investigating

  由于目标分子具有广谱的生物活性，合成四氢-β-咔啉的立体选择性方法引起了人们的极大兴趣。在植物界，胡豆素合酶通过色胺和塞洛甘宁的 Pictet-Spengler 反应催化 CC 偶联，专门形成 (S)-构型的四氢-β-咔啉 (S)-胡豆素。研究色胺与小分子量脂肪醛的生物催化 Pictet-Spengler 反应表明，胡豆苷合酶意外地获得了 (R) 构型的产物。开发一种有效的酶表达方法，可以制备转化各种醛，使产物的 ee 高达 >98%。借助该工具，实现了 (R)-harmicine 的化学酶两步合成，得到光学纯形式的 (R)-harmicine，总产率为 67%。
• Candida antarctica lipase B catalysed kinetic resolution of 1,2,3,4-tetrahydro-ß-carbolines: Substrate specificity
  作者：Barbara Kovács、Enikő Forró、Ferenc Fülöp

  DOI：10.1016/j.tet.2018.10.034

  日期：2018.11

  In the frame of substrate specificity, CAL-B-catalysed asymmetric N-alkoxycarbonylations of 1-substituted tetrahydro-ß-carbolines (Me, Et, Pr, iPr) have been studied. High enantioselectivities (>200) were observed, when alkoxycarbonylation of racemic compounds (±)-1,3,5,7 were performed in DIPE in the presence of phenyl allyl carbonate and Et3N at 60 °C using ultrasound shaking method. The reaction

  在底物特异性的框架内，已研究了CAL-B催化的1-取代的四氢-ß-咔啉（Me，Et，Pr，iPr）的不对称N-烷氧基羰基化。当在60℃下使用超声摇动法在碳酸苯丙酯和Et 3 N存在下，在DIPE中进行外消旋化合物的烷氧基羰基化（±）-1,3,5,7时，观察到高对映选择性（> 200）。反应时间随着C1上取代基尺寸的增加而显着增加。然而，事实证明，异丙基取代的化合物对于CAL-B的最佳活性而言过大。使用Pd 2（dba）3 .CHCl 3水解（R）-氨基甲酸酯对映异构体。得到游离胺的对映体，其ee值极好（> 99％）。
• Enantiopure Tetrahydro-β-carbolines via Pictet−Spengler Reactions with <i>N</i>-Sulfinyl Tryptamines
  作者：Christiaan Gremmen、Bianca Willemse、Martin J. Wanner、Gerrit-Jan Koomen

  DOI：10.1021/ol006034t

  日期：2000.6.1

  The influence of N-sulfinyl chiral auxiliaries on the stereochemistry of the Pictet-Spengler reaction has been investigated. From enantiopure (R)-N-beta-toluenesulfinyltryptamine a new and efficient route to enantiopure tetrahydro-beta-carbolines has been established.
• Monoamine Oxidase (MAO-N) Catalyzed Deracemization of Tetrahydro-β-carbolines: Substrate Dependent Switch in Enantioselectivity
  作者：Diego Ghislieri、Deborah Houghton、Anthony P. Green、Simon C. Willies、Nicholas J. Turner

  DOI：10.1021/cs400724g

  日期：2013.12.6

  The tetrahydro-beta-carboline (THBC) ring system is an important structural motif found in a large number of bioactive alkaloid natural products. Herein we report a broadly applicable method for the synthesis of enantiomerically pure beta-carbolines via a deracemization procedure employing the D9 and D11 variants of monoamine oxidase from Aspergillus niger (MAO-N) in combination with a nonselective chemical reducing agent. Biotransformations were performed on a preparative scale, leading to the synthesis of optically enriched products in excellent enantiomeric excess (e.e.; up to 99%) and isolated yield (up to 93%). Interestingly, a switch in enantioselectivity associated with the MAO-N variants is observed as the nature of the C-1 substituent of the THBC is varied. Molecular modeling provided an explanation for this observation and highlighted key active site residues which were modified, resulting in an increase in (R)-selectivity associated with the enzyme. These results provide insight into the factors which influence the selectivity of the MAO-N variants, and may offer a platform for future directed evolution projects aimed toward the challenge of engineering (R)-selective amine oxidase biocatalysts.