3-{2-[N-({[2-(Trimethylsilyl)ethyl]oxy}carbonyl)-N-hydroxylamino]ethyl}indole | 125109-08-2

• 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: 3-{2-[N-({[2-(Trimethylsilyl)ethyl]oxy}carbonyl)-N-hydroxylamino]ethyl}indole
• 英文别名: 2-trimethylsilylethyl N-hydroxy-N-[2-(1H-indol-3-yl)ethyl]carbamate
• CAS: 125109-08-2
• 化学式: C₁₆H₂₄N₂O₃Si
• 分子量: 320.464
• InChiKey: VUYCJSXNIWKSJX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  65.56
• 氢给体数：
  2.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  3-{2-[N-({[2-(Trimethylsilyl)ethyl]oxy}carbonyl)-N-hydroxylamino]ethyl}indole 在 palladium diacetate 、 potassium fluoride 、 氢氧化钾 、 四丁基氯化铵 、 sodium hydride 、 二异丁基氢化铝 、 甲酸:三乙胺 1:1 、 三苯基膦 、 sodium iodide 作用下， 以 乙二醇二甲醚 、 正己烷 、 二氯甲烷 、 二甲基亚砜 、 乙腈 为溶剂， 反应 16.75h， 生成 tert-butyl N-[(2R,3S)-18-methyl-7-oxa-5-thia-8,18-diazatetracyclo[9.7.0.02,8.012,17]octadeca-1(11),12,14,16-tetraen-3-yl]carbamate
  参考文献：
  名称：

  Antiviral and antitumor structure-activity relationship studies on tetracyclic eudistomines

  摘要：

  The in vitro antiviral and antitumor activities of (-)-debromoeudistomin K (1a) and 10 structural analogues (1b-1j and 11) were evaluated. The synthesis was accomplished with an intramolecular Pictet-Spengler condensation reaction as the key step. This examination revealed some structural and stereochemical features that are important for both the antiviral and antitumor activities. The most striking points for activity are the necessity to have the correct natural stereochemistry at both C(1) and C(13b) and the presence of the C(1)-NH2 substituent. As was revealed before with naturally isolated eudistomins a substituent in the indole ring greatly influences the biological activity. The 5-OMe derivative Ih shows high potency in both antiviral and antitumor models.

  DOI：

  10.1021/jm00095a019
• 作为产物：
  描述：

  芦竹碱 在 aluminum amalgam 、 水 、 sodium methylate 、 硫酸二甲酯 作用下， 以 1,4-二氧六环 、 甲醇 、 二氯甲烷 、 乙酸乙酯 为溶剂， 反应 26.0h， 生成 3-{2-[N-({[2-(Trimethylsilyl)ethyl]oxy}carbonyl)-N-hydroxylamino]ethyl}indole
  参考文献：
  名称：

  N-羟色胺衍生物对5-羟色胺和色胺受体的合成及受体亲和力 分子模型研究

  摘要：

  报道了一系列色胺的N-氧基衍生物（6-8、13-14）的血清素和色胺受体的合成及其亲和力。发现N-羟基色胺（6）是5-HT 1C受体的相对选择性的配体。受体结合数据通过分子建模研究解释，其中比较了5-HT 1A和5-HT 1C受体的结合位点。在5-HT 1A的螺旋7中存在但在5-HT 1C中不存在的天冬酰胺残基起关键作用。基于5-HT 1A七个跨膜区域的三维模型受体在这种天冬酰胺残基和螺旋3上的天冬氨酸残基的氧之一之间预计存在氢键相互作用，仅留下一个氧原子用于配体相互作用。在5-HT 1C中，螺旋3上天冬氨酸残基的两个氧自由地通过双氢键结合的配合物与6的N-羟基相互作用。N-甲氧基衍生物13缺乏这种额外的氢键可能性并且缺乏结合亲和力，大概是由于静电排斥的结果。

  DOI：

  10.1002/recl.19931120210

文献信息

• Intramolecular Pictet-Spengler reaction of Nb-Alkoxytryptamines. 4. A study towards diastereocontrol in the synthesis of tetracyclic eudistomins
  作者：Jan H. van Maarseveen、Hans W. Scheeren、Chris G. Kruse

  DOI：10.1016/s0040-4020(01)80376-8

  日期：1993.3

  methylated derivative was also synthesized giving the interesting cis/trans pentacyclic spiro compounds 19 and 20. These results are interpreted in terms of a kinetically favoured electrophilic attack at the indole-3 position, whereas β-carboline formation is the result of a slower route via electrophilic attack at the indole-2 position.

  描述了在合成四环大黄连素中分子内Pictet-Spengler缩合的非对映选择性。N b-烷氧基色胺15a–m与不同大小的基团R 2合成。7成员草硫氮杂ze环的闭合以66–98％的产率完成。使用分子内方法，可以实现非天然反式异构体的非对映选择性。还合成了吲哚甲基化衍生物，得到了有趣的顺式/反式五环螺化合物19和20。这些结果被解释为在吲哚3位置的动力学上有利于亲电子的攻击，而β-咔啉的形成是在吲哚2位置上通过亲电子攻击的较慢途径的结果。
• Antiviral and tumor cell antiproliferative SAR studies on tetracyclic eudistomins—II
  作者：Jan H. van Maarseveen、Hans W. Scheeren、Erik De Clercq、Jan Balzarini、Chris G. Kruse

  DOI：10.1016/s0968-0896(97)00034-5

  日期：1997.5

  In a search for the minimum pharmacophore of the naturally occurring tetracyclic eudistomins, five structural analogues (4-8) were evaluated for their in vitro antiviral and tumor cell antiproliferative activities. For the synthesis of these derivatives both intra- and intermolecular Pictet-Spengler reactions have been used. Opening of the beta-carboline annulated 7-membered D-ring in 6 and 7 resulted in a complete loss of activity. On the other rand, replacement of either the oxygen atom or the sulfur atom in the 7-membered ring by a methylene group in 5 and 8, respectively, is allowed. These results combined with previous SAR data underline the crucial importance of the D-ring in eudistomins as a scaffold for the correct positioning of both basic nitrogen atoms. Also bioisosteric replacement of the bicyclic indole system with a dimethoxyphenyl group, to give the isoquinoline skeleton, is allowed. The tricyclic isoquinoline derivative 4 is, so far, the most promising antiviral analogue; it combines a high potency (MIG at 100 ng/mL (340 nM)) with high MCC/MIC ratios (ranging from 1000 to 5000 against HSV-1, HSV-2, vaccinia virus, and vesicular stomatitis virus). (C) 1997 Elsevier Science Ltd.
• Intramolecular Pictet-Spengler reaction of N-alkoxytryptophans and tryptamines. 2. Synthesis of Corynanthe alkaloid derivatives containing a tetrahydro-1,2-oxazine as the D ring
  作者：Pedro H. H. Hermkens、Jan H. Van Maarseveen、Harry W. Berens、Jan M. M. Smits、Chris G. Kruse、Hans W. Scheeren

  DOI：10.1021/jo00294a041

  日期：1990.3
• Intramolecular Pictet-Spengler reaction of N-alkoxy tryptamines I. Synthesis of (±)-Deamino-debromo-Eudistomin L
  作者：Pedro H.H. Hermkens、Jan H. v.Maarseveen、Chris G. Kruse、Hans W. Scheeren

  DOI：10.1016/s0040-4039(01)80568-2

  日期：1989.1
• HERMKENS, PERDO H. H.;MAARSEVEEN, JAN H. V.;KRUSE, CHRIS G.;SCHEEREN, HAN+, TETRAHEDRON LETT., 30,(1989) N7, C. 5009-5012
  作者：HERMKENS, PERDO H. H.、MAARSEVEEN, JAN H. V.、KRUSE, CHRIS G.、SCHEEREN, HAN+

  DOI：——

  日期：——