1-tert-Butyl-2,3,4,9-tetrahydro-1H-β-carboline; hydrochloride | 6650-06-2

• 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-tert-Butyl-2,3,4,9-tetrahydro-1H-β-carboline; hydrochloride
• CAS: 6650-06-2
• 化学式: C₁₅H₂₀N₂*ClH
• 分子量: 264.798
• InChiKey: WZGGKBDFLOFSDV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.82
• 重原子数：
  18.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  27.82
• 氢给体数：
  2.0
• 氢受体数：
  1.0

反应信息

• 作为反应物：
  描述：

  1-tert-Butyl-2,3,4,9-tetrahydro-1H-β-carboline; hydrochloride 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， 以96%的产率得到
  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
• 作为产物：
  描述：

  色胺盐酸盐 、 特戊醛 生成 1-tert-Butyl-2,3,4,9-tetrahydro-1H-β-carboline; hydrochloride
  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