methyl tetrahydro-β-carboline-1-acetate | 61756-61-4

• 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: methyl tetrahydro-β-carboline-1-acetate
• 英文别名: (1RS)-1,2,3,4-tetrahydro-1-<(methoxycarbonyl)methyl>-β-carboline；1-methoxycarbonylmethyl-1,3,4,9-tetrahydro-β-carboline；(2,3,4,9-tetrahydro-1H-β-carbolin-1-yl)-acetic acid methyl ester；methyl 2-(2,3,4,9-tetrahydro-1H-pyrido[3,4-b]indol-1-yl)acetate
• CAS: 61756-61-4
• 化学式: C₁₄H₁₆N₂O₂
• 分子量: 244.293
• InChiKey: GOFDFHUHNZVYHW-UHFFFAOYSA-N

物化性质

• 沸点：
  421.8±35.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  18
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 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：

  methyl tetrahydro-β-carboline-1-acetate 在 水 、 potassium carbonate 、 lithium hydroxide 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 1-carboxymethyl-N-phenylacetyl-1,3,4,9-tetrahydro-β-carboline
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Novel Tetrahydro-β-carboline Derivatives as Antitumor Growth and Metastasis Agents through Inhibiting the Transforming Growth Factor-β Signaling Pathway

  摘要：

  The transforming growth factor beta (TGF beta) signaling cascade is considered as one of the pivotal oncogenic pathways in most advanced cancers. Inhibition of the TGF beta signaling pathway by specific antagonists, neutralizing antibodies, or small molecules is considered as an effective strategy for the treatment of tumor growth and metastasis. Here we demonstrated the identification of a series of tetrahydro-beta-carboline derivatives from virtual screening which potentially inhibit the TGF beta signaling pathway. Optimization of the initial hit compound 2-benzoyl-1,3,4,9-tetrahydro-beta-carboline (8a) through substitution at different positions to define the structure-activity relationship resulted in the discovery of potent inhibitors of the TGF beta signaling pathway. Among them, compound 8d, one of the tested compounds, not only showed potent inhibition of lung cancer cell proliferation and migration in vitro but also strongly suppressed growth of lung cancer and breast cancer in vivo.

  DOI：

  10.1021/jm401117t
• 作为产物：
  描述：

  N-亚苄基-2-(1H-吲哚-3-基)乙胺 在 sodium tetrahydroborate 、 palladium on activated charcoal 、 氢气 、 溶剂黄146 、 三氟乙酸 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 35.0h， 生成 methyl tetrahydro-β-carboline-1-acetate
  参考文献：
  名称：

  Design and synthesis of Pictet–Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death

  摘要：

  A series of Pictet-Spengler condensation derivatives (tetrahydro-beta-carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RAS(V12) tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2012.06.077

文献信息

• Synthesis of ajmalicine derivatives using Wittig-Horner and Knoevenagel reactions
  作者：Ahcène Boumendjel、Jean-Marc Nuzillard、Georges Massiot

  DOI：10.1016/s0040-4039(99)01921-8

  日期：1999.12

  2-(2,3,4,9-Tetrahydro-1H-β-carbolin-1-yl)acetaldehyde, synthesized from tryptamine in five steps, is easily homologated by Wittig-Horner or Knoevenagel reactions to substituted acrylates. These highly reactive compounds are key intermediates in the synthesis of analogs of the natural indol alkaloid ajmalicine.

  用五步步骤从色胺中合成的2-（2,3,4,9-四氢-1 H -β-咔啉-1-基）乙醛很容易通过Wittig-Horner或Knoevenagel反应同化为取代的丙烯酸酯。这些高反应性化合物是天然吲哚生物碱阿兹玛林类似物合成中的关键中间体。
• Trapping of iminiums by the indole nucleus during catalytic hydrogenation of nitriles: a rapid synthesis of tetrahydro-β-carbolines
  作者：Khalid Diker、Michèle Döé de Maindreville、Jean Lévy

  DOI：10.1016/0040-4039(95)00293-l

  日期：1995.4

  Reductive self-condensation of indole acetonitrile upon catalytic hydrogenation over Pd·C in acetic acid yielded 1-(3-indolylmethyl)-1,2,3,4-tetrahydro-β-carboline. Hydrogenating 3,4-dimethoxyphenylacetonitrile failed to give tetrahydropapaverine, but a cross reaction between indole acetonitrile and 3,4-dimethoxyphenylacetonitrile allowed isolation of 1-(3,4-dimethoxybenzyl)-1,2,3,4-tetrahydro-β-carboline

  在乙酸中Pd·C催化加氢后，吲哚乙腈的还原自缩合​​反应生成1-（3-吲哚基甲基）-1,2,3,4-四氢-β-咔啉。氢化3,4-二甲氧基苯基乙腈未能得到四氢罂粟碱，但吲哚乙腈与3,4-二甲氧基苯基乙腈之间的交叉反应可分离出1-（3,4-二甲氧基苄基）-1,2,3,4-四氢-β-咔啉，否则可通过将色胺和3,4-二甲氧基苯基乙腈的混合物催化加氢制得（76％）。除了易于接近育亨宾骨架外，该反应还为四氢-β-咔啉的有用的一般合成方法开辟了道路。
• Synthetic Study towards Strictamine: The Oxidative Coupling Approach
  作者：Jieping Zhu、Weiwu Ren、Nicholas Tappin、Qian Wang

  DOI：10.1055/s-0033-1339472

  日期：——

  A synthetic approach featuring a key intramolecular oxidative coupling of a dianion for the formation of the C7–C16 bond was exploited aiming at the synthesis of strictamine. Treatment of substituted tetrahydrocarboline with LHMDS at –78 °C followed by iodine at room temperature afforded a tetracyclic compound, a substructure of eburnane-type alkaloid, via the formation of the ­Na–C16 bond.

  为了合成严格胺，开发了一种合成方法，其特征在于形成 C7-C16 键的二价阴离子的关键分子内氧化偶联。在 –78 °C 下用 LHMDS 处理取代的四氢咔啉，然后在室温下用碘处理，通过形成 Na-C16 键，得到四环化合物，这是 eburnane 型生物碱的亚结构。
• Synthesis of 3-(indol-2-yl)-propenoate derivatives of tryptamine, valuable intermediates for the preparation of indole alkaloids
  作者：Patrick D Bailey、Sean P Hollinshead

  DOI：10.1016/s0040-4039(00)96233-6

  日期：1987.1

  A simple three step route to 3-(indol-2-yl)-propenoate derivatives of tryptamine has been developed, involving the base-induced ring-opening of protected tetrahydro-β-carbolines that result from a modified Pictet-Spengler reaction.

  已经开发了一种简单的三步合成色胺的3-（吲哚-2-基）-丙烯酸酯衍生物的方法，涉及碱诱导的由修饰的Pictet-Spengler反应产生的受保护的四氢-β-咔啉的开环。
• Azocinoindole Synthesis by a Gold(I)-Catalyzed Ring Expansion of 2-Propargyl-β-Tetrahydrocarboline
  作者：Lei Zhang、Lina Chang、Hongwen Hu、Huaqin Wang、Zhu-Jun Yao、Shaozhong Wang

  DOI：10.1002/chem.201304524

  日期：2014.3.3

  A new methodology taking advantage of gold(I)‐catalyzed ring expansion has been developed to assemble tricyclic 1H‐azocino[5,4‐b]indoles from 2‐propargyl‐β‐tetrahydrocarbolines. The azocinoindoles were obtained in moderate to excellent yields; the structure of which was established by X‐ray crystallographic analysis. A mechanism involving regioselective intramolecular hydroarylation, [1,2]‐alkenyl

  的新方法利用的金（I） -催化的环扩大已经发展到三环1组装ħ -azocino并[5,4- b〕吲哚由2-炔丙基-β-tetrahydrocarbolines。以中等至极高的收率获得了偶氮基吲哚。其结构通过X射线结晶分析确定。涉及区域选择性分子内hydroarylation所述的机构，提出了[1,2] -烯基迁移和碳-碳键的断裂。