(S)-1-(tert-butyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole | 252638-17-8

• 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: (S)-1-(tert-butyl)-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• 英文别名: 1-tert-butyl-1,2,3,4-tetrahydro-1H-pyrido[3,4-b]indole；(1S)-1-tert-butyl-2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indole
• CAS: 252638-17-8
• 化学式: C₁₅H₂₀N₂
• 分子量: 228.337
• InChiKey: JQQSVGOVEHJNQF-CQSZACIVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  17
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 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：

  特戊醛 在 硼烷铵络合物 、 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 (S)-1-(tert-butyl)-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

• Asymmetric Synthesis of Sterically Hindered 1-Substituted Tetrahydro-β-carbolines Enabled by Imine Reductase: Enzyme Discovery, Protein Engineering, and Reaction Development
  作者：Yitong Li、Xiaoping Yue、Zhining Li、Zedu Huang、Fener Chen

  DOI：10.1021/acs.orglett.3c00147

  日期：2023.3.3

  We report the discovery of a new imine reductase (IRED), named AtIRED, by genome mining. Site-saturation mutagenesis on AtIRED generated two single mutants M118′L and P120′G and the double mutant M118′L/P120′G with improved specific activity toward sterically hindered 1-substituted dihydro-β-carbolines. The synthetic potential of these engineered IREDs was showcased by the preparative-scale synthesis

  我们报告了通过基因组挖掘发现了一种名为At IRED 的新亚胺还原酶 (IRED)。At IRED上的定点饱和诱变产生了两个单突变体 M118'L 和 P120'G 以及双突变体 M118'L/P120'G，它们对位阻 1-取代的二氢-β-咔啉具有更高的比活性。九种手性 1-取代四氢-β-咔啉 (THβC) 的制备规模合成展示了这些工程 IRED 的合成潜力，包括 (S)-1-t-丁基-THβC和( S )-1- t -戊基-THβC，分离产率为 30–87%，具有出色的光学纯度 (98–99% ee)。
• Asymmetric Hydrogenation of Cyclic Imines with an Ionic Cp*Rh(III) Catalyst
  作者：Chaoqun Li、Jianliang Xiao

  DOI：10.1021/ja8050958

  日期：2008.10.8

  When associated with a noncoordinating bulky conunteranion, a cationic Cp*Rh(III)-diamine catalyst displayed excellent enantioselectivities in asymmetric hydrogenation of cyclic imines, affording bioactive tetrahydroisoquinolines and tetrahydro-beta-carbolines frequently with 99% ee's.