2-hydroxymethyl-5-methoxyindole-O-acetate | 65746-97-6

• 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
• 英文名称: 2-hydroxymethyl-5-methoxyindole-O-acetate
• 英文别名: (5-methoxy-1H-indol-2-yl)methyl acetate；2-acetoxymethyl-5-methoxy-indole
• CAS: 65746-97-6
• 化学式: C₁₂H₁₃NO₃
• 分子量: 219.24
• InChiKey: BMVCPNZGVZZRBU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-hydroxymethyl-5-methoxyindole-O-acetate 在 哌啶 、 三氯氧磷 作用下， 以 甲醇 为溶剂， 反应 2.83h， 生成 3-(2-hydroxymethyl-5-methoxy-1H-indol-3-yl)-1-(4-pyridinyl)-2-propen-1-one
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

  摘要：

  Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents.

  DOI：

  10.1021/jm501997q
• 作为产物：
  描述：

  5-甲氧基吲哚-2-羧酸 在 盐酸 、 lithium aluminium tetrahydride 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 28.0h， 生成 2-hydroxymethyl-5-methoxyindole-O-acetate
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Indolyl-Pyridinyl-Propenones Having Either Methuosis or Microtubule Disruption Activity

  摘要：

  Methuosis is a form of nonapoptotic cell death characterized by an accumulation of macropinosome-derived vacuoles with eventual loss of membrane integrity. Small molecules inducing methuosis could offer significant advantages compared to more traditional anticancer drug therapies that typically rely on apoptosis. Herein we further define the effects of chemical substitutions at the 2- and 5-indolyl positions on our lead compound 3-(5-methoxy-2-methyl-1H-indol-3-yl)-1-(4-pyridinyl)-2-propene-1-one (MOMIPP). We have identified a number of compounds that induce methuosis at similar potencies, including an interesting analogue having a hydroxypropyl substituent at the 2-position. In addition, we have discovered that certain substitutions on the 2-indolyl position redirect the mode of cytotoxicity from methuosis to microtubule disruption. This switch in activity is associated with an increase in potency as large as 2 orders of magnitude. These compounds appear to represent a new class of potent microtubule-active anticancer agents.

  DOI：

  10.1021/jm501997q

文献信息

• Synthesis of Indole/Benzofuran-Containing Diarylmethanes through Palladium-Catalyzed Reaction of Indolylmethyl or Benzofuranylmethyl Acetates with Boronic Acids
  作者：Antonella Goggiamani、Antonia Iazzetti、Antonio Arcadi、Andrea Calcaterra、Marco Chiarini、Giancarlo Fabrizi、Andrea Fochetti、Federico Marrone、Vincenzo Marsicano、Andrea Serraiocco

  DOI：10.1055/s-0041-1737275

  日期：2022.2

  The palladium-catalyzed synthesis of indole/benzofuran-containing diarylmethanes starting from indolylmethyl or benzofuranylmethyl acetates with boronic acids has been investigated. The success of the reaction is influenced by the choice of precatalyst: with indolylmethyl acetates the reaction works well with [Pd(η3-C3H5)Cl]2/XPhos while with benzofuranylmethyl acetates Pd2(dba)3/XPhos is more efficient

  已经研究了从吲哚甲基或苯并呋喃甲基乙酸酯与硼酸开始钯催化合成含有吲哚/苯并呋喃的二芳基甲烷。反应的成功受预催化剂选择的影响：对于吲哚基乙酸甲酯，该反应与 [Pd(η 3 -C 3 H 5 )Cl] 2 /XPhos反应良好，而对于苯并呋喃基乙酸甲酯 Pd 2 (dba) 3 /XPhos 则反应良好更高效。良好的高产率和实验程序的简单性使该方案成为制备 2-和 3-取代吲哚和 2-苯并[ b]的通用合成工具]呋喃。该方法可以有利地扩展到扎鲁司特的关键前体的制备。
• Method for the production of indolyl lactones
  申请人：——

  公开号：US04118395A1

  公开（公告）日：1978-10-03

  A method for the production of indolyl lactones of the formula ##STR1## wherein R.sub.1 is hydrogen, halogen, or an alkoxy group having 1 to 4 C atoms and R.sub.3 is hydrogen, characterized in the manner that one reacts a 2-hydroxymethylindole of the formula ##STR2## wherein R.sub.1 has the above named meaning and R.sub.2 is an alkanoyl group or a phenyl alkanoyl group, with an .alpha.-diazoester of the formula ##STR3## wherein R.sub.3 has the above named meaning and R.sub.4 is an alkyl group having 1 to 4 C atoms and a, benzyl group, to a 3-indolyl acetic acid ester of the formula ##STR4## wherein R.sub.1, R.sub.2, R.sub.3 and R.sub.4 have the above named meanings, saponifies the thus obtained 3-indolyl acetic acid ester of the formula (IV) to the 3-indolyl acetic acid of the formula ##STR5## wherein R.sub.1 and R.sub.3 have the above named meaning, and the latter is dehydrated to indolyl lactone with the formula (I).

  一种制备式为##STR1##的吲哚内酯的方法，其中R.sub.1为氢、卤素或具有1至4个碳原子的烷氧基，R.sub.3为氢，其特征在于将式为##STR2##的2-羟甲基吲哚（其中R.sub.1具有上述命名的含义，R.sub.2为烷酰基或苯基烷酰基）与式为##STR3##的.alpha.-重氮乙酸酯（其中R.sub.3具有上述命名的含义，R.sub.4为具有1至4个碳原子的烷基和苄基）反应，得到式为##STR4##的3-吲哚乙酸酯，将所得的式（IV）的3-吲哚乙酸酯皂化为式为##STR5##的3-吲哚乙酸（其中R.sub.1和R.sub.3具有上述命名的含义），并将后者脱水为式（I）的吲哚内酯。
• Reactivity of Indolylmethylacetates with N, O, and S Soft Nucleophiles: Evidence of 2‐Alkylideneindolenines and 3‐Alkylideneindoleninium Generation by ESI‐MS and IRMPD Spectroscopy
  作者：Antonio Arcadi、Giel Berden、Alessia Ciogli、Davide Corinti、Maria Elisa Crestoni、Martina De Angelis、Giancarlo Fabrizi、Antonella Goggiamani、Antonia Iazzetti、Federico Marrone、Vincenzo Marsicano、Jos Oomens、Andrea Serraiocco

  DOI：10.1002/ejoc.202201166

  日期：2022.11.18

  The synthesis of (aminomethyl), (tosylmethyl), and (aryloxymethyl) indoles starting from indolylmethylacetates with various nucleophiles has been developed. The experimental evidence of the in situ generation of 2-alkylideneindolenines and 3-alkylideneindoleninium as reaction intermediates has been provided through ESI-MS and IRMPD spectroscopy analysis.

  从吲哚甲基乙酸酯和各种亲核试剂开始，合成了（氨基甲基）、（甲苯磺酰甲基）和（芳氧基甲基）吲哚。通过 ESI-MS 和 IRMPD 光谱分析提供了原位生成 2-亚烷基吲哚和 3-亚烷基吲哚作为反应中间体的实验证据。
• Synthesis of 3-substituted 2,3-dihydropyrazino[1,2-<i>a</i>]indol-4(1<i>H</i>)-ones by sequential reactions of 2-indolylmethyl acetates with α-amino acids
  作者：Antonella Goggiamani、Antonio Arcadi、Alessia Ciogli、Martina De Angelis、Stefano Dessalvi、Giancarlo Fabrizi、Federica Iavarone、Antonia Iazzetti、Alessio Sferrazza、Roberta Zoppoli

  DOI：10.1039/d3ra01335a

  日期：——

  The synthesis of 2,3-dihydropyrazino[1,2-a]indol-4(1H)-ones from the sequential reaction of amino acid methyl esters with readily available indole-2-ylmethyl acetates is described. The reaction proceeds in situ under basic conditions of highly unstable and reactive 2-alkylideneindolenines followed by Michael-type addition of α-amino acid methyl esters/intramolecular cyclization.

  描述了通过氨基酸甲酯与容易获得的吲哚-2-基甲基乙酸酯的连续反应合成2,3-二氢吡嗪基[1,2- a ]吲哚-4( 1H )-酮。该反应在高度不稳定和反应性 2-亚烷基假吲哚的碱性条件下原位进行，然后进行 α-氨基酸甲酯的迈克尔型加成/分子内环化。
• US4118395A
  申请人：——

  公开号：US4118395A

  公开（公告）日：1978-10-03