3-(2-羟基乙基)-5-甲氧基-1H-吲哚-1-羧酸叔丁酯 | 898746-70-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 中文名称: 3-(2-羟基乙基)-5-甲氧基-1H-吲哚-1-羧酸叔丁酯
• 英文名称: tert-butyl 3-(2-hydroxyethyl)-5-methoxy-1H-indole-1-carboxylate
• 英文别名: N-Boc-5-methoxytryptophol；tert-butyl 3-(2-hydroxyethyl)-5-methoxyindole-1-carboxylate
• CAS: 898746-70-8
• 化学式: C₁₆H₂₁NO₄
• 分子量: 291.347
• InChiKey: LOYCSWSQMLVADI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  60.7
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-(2-羟基乙基)-5-甲氧基-1H-吲哚-1-羧酸叔丁酯 在 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 2-碘酰基苯甲酸 作用下， 以 二氯甲烷 、 水 、 二甲基亚砜 为溶剂， 反应 8.5h， 生成 6,5′-dimethyl hyrtiosulawesine
  参考文献：
  名称：

  Synthesis of 1-indolyl substituted β-carboline natural products and discovery of antimalarial and cytotoxic activities

  摘要：

  A series of 1-indolyl substituted beta-carbolines including the natural products hyrtiosulawesine, pityriacitrin and pityriacitrin B were prepared via Pictet-Spengler condensation oxidation strategy from the corresponding indolyl-acetaldehydes and substituted tryptamines. Efforts to prepare the C-1 methylene-linked beta-carboline analogues for structure activity relationship studies were unsuccessful. Biological evaluation revealed two analogues (5 and 41) to exhibit weak inhibition of phospholipase A(2) (IC50 171 and 131 mu M, respectively), two to act as antioxidants (3 and 43), and 12 analogues with activity towards a chloroquine-resistant strain (FcB1) of Plasmodium falciparum (IC50 1.0-23 mu M). Testing against a panel of 60 human tumour cell lines revealed a general lack of cytotoxic effect for most of the compounds with the exception of beta-carboline 42 exhibiting modest antileukaemic activity towards the HL-60(TB) cell line (LC50 4.2 mu M). In addition, two novel structures (30 and 32) resulting from aldol condensation followed by Pictet-Spengler cyclisation displayed cytotoxicity with pronounced subpanel specificities towards colon cancer (COLO 205 and HCC-2998) cell lines. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2014.05.068
• 作为产物：
  描述：

  5-甲氧基吲哚-3-乙醇 在 咪唑 、 四丁基氟化铵 、 sodium hydride 作用下， 以 四氢呋喃 、 乙酸乙酯 、 N,N-dimethyl-d₆-formamide 为溶剂， 反应 28.25h， 生成 3-(2-羟基乙基)-5-甲氧基-1H-吲哚-1-羧酸叔丁酯
  参考文献：
  名称：

  亚硝酸盐催化色胺/色酚的经济且可持续的溴环化反应以批量和流动方式获得六氢吡咯并[2,3-b]吲哚/四氢呋喃吲哚啉

  摘要：

  成功实现了高效、简洁的溴环化反应，将色胺/色酚衍生物以经济、绿色的方式转化为有价值的HPI/TFI支架。此外，溴环化和芳香溴化的可控级联转化也顺利实现，形成二溴化HPI和TFI。批量生产和连续流生产均可成功扩大生产规模。与以前的所有方法相比，我们的工艺最显着的特点是产生的水是主要废物。值得注意的是，这种新方案的成功应用已被药物和天然产物合成所证明。

  DOI：

  10.1016/j.cclet.2023.109280

文献信息

• Au(I)-Catalyzed Domino Cyclization of 1,6-Diynes Incorporated with Indole
  作者：Guzhou Chen、Peng-Yu Liu、Huanhuan Zou、Jiadong Hu、Xiaowu Fang、Dongyang Xu、Yu-Peng He、Hongbo Wei、Weiqing Xie

  DOI：10.1021/acs.orglett.1c00411

  日期：2021.3.19

  We disclose herein a Au(I)-catalyzed domino cyclization of 1,6-diynes incorporated with indole. This protocol enabled the diastereoselective buildup of indole-fused azabicyclo[3.3.1]nonanes from linear precursors. Density functional theory calculations showed that the reaction proceeded via an unprecedented cascade dearomatization/rearomatization/dearomatization process. Independent gradient model

  我们在本文中公开了与吲哚结合的1，6-二炔的Au（I）催化的多米诺环化。该协议使线性前体的吲哚稠合的氮杂双环[3.3.1]壬烷非对映选择性地形成。密度泛函理论计算表明，反应是通过空前的级联脱芳香化/再芳香化/脱芳香化过程进行的。独立的梯度模型分析表明，远端炔烃与Au /近端复合物之间的非共价吸引相互作用是第一步螺环化步骤的化学选择性的原因。
• Highly Enantioselective Copper- and Iron-Catalyzed Intramolecular Cyclopropanation of Indoles
  作者：Huan Xu、Yi-Pan Li、Yan Cai、Guo-Peng Wang、Shou-Fei Zhu、Qi-Lin Zhou

  DOI：10.1021/jacs.7b03086

  日期：2017.6.14

  We report the first intramolecular enantioselective cyclopropanation of indoles, which was accomplished in good to high yield (up to 94%) with excellent enantioselectivity (up to >99.9% ee) by using copper or iron complexes of chiral spiro bisoxazolines as catalysts. This reaction is a straightforward, efficient method for constructing polycyclic compounds with an all-carbon quaternary stereogenic

  我们报告了首个吲哚分子内对映选择性环丙烷化反应，该反应是通过使用手性螺环双恶唑啉的铜或铁配合物，以良好至高收率（高达94％）和优异的对映选择性（高达> 99.9％ee）完成的。该反应是一种直接有效的方法，用于构建在吲哚骨架的3位具有全碳四级立体中心的多环化合物，该骨架是许多天然产物和生物活性化合物共有的核心结构。
• Enantioselective Halocyclization of Indole Derivatives: Using 1,3-Dihalohydantoins with Anionic Chiral Co(III) Complexes
  作者：Ting-Ting Sun、Kun Liu、Shun-Xin Zhang、Jie Yu、Chun-Ru Wang、Chuan-Zhi Yao

  DOI：10.1055/a-1310-5213

  日期：2021.4

  Highly enantioselective halocyclization reactions of indole derivatives, including tryptophols and tryptamines, have been accomplished by means of anionic chiral Co(III) complexes and 1,3-dihalohydantoins (as little as 0.50 equiv). 3-Halo-fused indolines were obtained in excellent yields (up to 98%) and enantioselectivities (up to 98% ee), employing the chiral anion phase-transfer-catalysis strategy.

  摘要：利用阴离子手性Co（III）配合物和1,3-二卤代海因杜因（仅需0.50当量）实现了吲哚衍生物的高度对映选择性卤环化反应，包括色氨酸醇和色氨酸胺。采用手性阴离子相转移催化策略，得到了3-卤代融合吲哚烷，收率高（高达98％）和对映选择性高（高达98％ee）。
• Highly Asymmetric Bromocyclization of Tryptophol: Unexpected Accelerating Effect of DABCO-Derived Bromine Complex
  作者：Huan Liu、Guangde Jiang、Xixian Pan、Xiaolong Wan、Yisheng Lai、Dawei Ma、Weiqing Xie

  DOI：10.1021/ol5004109

  日期：2014.4.4

  Highly asymmetric bromocyclization of tryptophol by using chiral anionic phase-transfer catalyst and DABCO-derived brominating reagent is described. Optimization of the reaction conditions revealed that the reaction rate was accelerated together with improvement of enantioselectivity by addition of catalytic DABCO-derived brominating reagent. From tryptophol, 3-bromofuroindoline could be directly obtained in excellent enantioselectivities by employing this novel methodology.
• Synthesis of 1-indolyl substituted β-carboline natural products and discovery of antimalarial and cytotoxic activities
  作者：Lydia P.P. Liew、Jessica M. Fleming、Arlette Longeon、Elisabeth Mouray、Isabelle Florent、Marie-Lise Bourguet-Kondracki、Brent R. Copp

  DOI：10.1016/j.tet.2014.05.068

  日期：2014.8

  A series of 1-indolyl substituted beta-carbolines including the natural products hyrtiosulawesine, pityriacitrin and pityriacitrin B were prepared via Pictet-Spengler condensation oxidation strategy from the corresponding indolyl-acetaldehydes and substituted tryptamines. Efforts to prepare the C-1 methylene-linked beta-carboline analogues for structure activity relationship studies were unsuccessful. Biological evaluation revealed two analogues (5 and 41) to exhibit weak inhibition of phospholipase A(2) (IC50 171 and 131 mu M, respectively), two to act as antioxidants (3 and 43), and 12 analogues with activity towards a chloroquine-resistant strain (FcB1) of Plasmodium falciparum (IC50 1.0-23 mu M). Testing against a panel of 60 human tumour cell lines revealed a general lack of cytotoxic effect for most of the compounds with the exception of beta-carboline 42 exhibiting modest antileukaemic activity towards the HL-60(TB) cell line (LC50 4.2 mu M). In addition, two novel structures (30 and 32) resulting from aldol condensation followed by Pictet-Spengler cyclisation displayed cytotoxicity with pronounced subpanel specificities towards colon cancer (COLO 205 and HCC-2998) cell lines. (C) 2014 Elsevier Ltd. All rights reserved.