[N-(trimethylsilyl)methyl]-L-phenylalanine methyl ester | 220438-32-4

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: [N-(trimethylsilyl)methyl]-L-phenylalanine methyl ester
• 英文别名: methyl ((trimethylsilyl)methyl)-L-phenylalaninate；methyl (2S)-3-phenyl-2-(trimethylsilylmethylamino)propanoate
• CAS: 220438-32-4
• 化学式: C₁₄H₂₃NO₂Si
• 分子量: 265.428
• InChiKey: CLLWXKQXUXSDFR-ZDUSSCGKSA-N

物化性质

• 沸点：
  329.6±32.0 °C(Predicted)
• 密度：
  0.984±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.24
• 重原子数：
  18.0
• 可旋转键数：
  6.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  [N-(trimethylsilyl)methyl]-L-phenylalanine methyl ester 在 2,4,6-三甲基吡啶 、 盐酸 、 N-羟基-7-氮杂苯并三氮唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 二氯甲烷 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 2-({2-[2-((2-benzyloxycarbonylaminoacetyl){[(2,4-dimethoxyphenyl)dimethylsilanyl]methyl}amino)-3-phenylpropionylamino]acetyl}trimethylsilanylmethylamino)-3-phenylpropionic acid methyl ester
  参考文献：
  名称：

  Building Functionalized Peptidomimetics:  Use of Electroauxiliaries for Introducing N-Acyliminium Ions into Peptides

  摘要：

  A series of silyl-substituted amino acids have been synthesized, inserted into peptides, and then employed as precursors for oxidatively generating reactive N-acyliminium ions. Both electrochemical and chemical oxidation procedures have been employed. N-Acyliminium ion generation in a solid-phase substrate as well as application to a small library of functionalized dipeptides has been demonstrated. Limitations in terms of how electron-rich the silyl groups can be as well as the compatibility of multiple silyl groups within a longer peptide are defined.

  DOI：

  10.1021/ja064737l
• 作为产物：
  描述：

  L-苯丙氨酸甲酯盐酸盐 、 氯甲基三甲基硅烷 在 potassium carbonate 、 potassium iodide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以69%的产率得到[N-(trimethylsilyl)methyl]-L-phenylalanine methyl ester
  参考文献：
  名称：

  建立功能化的拟肽药物：新型电助剂和使用化学氧化剂将N-酰基亚胺离子引入肽中。

  摘要：

  [反应：见正文]作为将N-酰基亚胺离子插入肽中的方法，已经研究了用化学氧化剂从肽底物上去除电助剂的方法。为此，发现使用硝酸铈铵可容易地裂解4-甲氧基苯基二甲基甲硅烷基和2，4-二甲氧基苯基二甲基甲硅烷基电助剂。在两组中，2,4-二甲氧基苯基二甲基甲硅烷基电助剂在氧化条件下最不稳定。氧化反应被证明与固相底物的使用相容。

  DOI：

  10.1021/ol034872s

文献信息

• Multifunctional Building Blocks Compatible with Photoredox-Mediated Alkylation for DNA-Encoded Library Synthesis
  作者：Shorouk O. Badir、Jaehoon Sim、Katelyn Billings、Adam Csakai、Xuange Zhang、Weizhe Dong、Gary A. Molander

  DOI：10.1021/acs.orglett.9b04568

  日期：2020.2.7

  DNA-encoded library (DEL) technology has emerged as a novel interrogation modality for ligand discovery in the pharmaceutical industry. Given the increasing demand for a higher proportion of C(sp3)-hybridized centers in DEL platforms, a photoredox-mediated cross-coupling and defluorinative alkylation process is introduced using commercially available alkyl bromides and structurally diverse α-silylamines

  DNA编码文库（DEL）技术已经成为制药业发现配体的一种新型询问方式。鉴于在DEL平台中对更高比例的C（sp3）杂化中心的需求不断增加，采用了可商购的烷基溴化物和结构多样的α-甲硅烷基胺，引入了光氧化还原介导的交叉偶联和脱氟烷基化工艺。值得注意的是，对于多种基于氨基酸的有机硅烷的掺入，不需要胺的保护基策略，从而为进一步衍生化提供了关键的支化点。
• Accessing Aliphatic Amines in C–C Cross-Couplings by Visible Light/Nickel Dual Catalysis
  作者：Weizhe Dong、Shorouk O. Badir、Xuange Zhang、Gary A. Molander

  DOI：10.1021/acs.orglett.1c01207

  日期：2021.6.4

  desilylation of α-silylamines upon single-electron transfer (SET) facilitated by carbonate, α-amino radicals are generated regioselectively, which then engage in nickel-mediated C–C coupling. The reaction displays high chemoselectivity for C–C over C–N bond formation. Highly functionalized pharmacophores and peptides are also amenable.

  开发了芳基卤化物的一般氨基烷基化，克服了镍介导的 C-C 偶联中游离胺的不耐受性。这种转化具有广泛的官能团耐受性和高效率。利用碳酸盐促进的单电子转移（SET）时α-甲硅烷胺的快速脱甲硅烷基化，区域选择性地产生α-氨基自由基，然后参与镍介导的C-C偶联。该反应对 C-C 的化学选择性高于 C-N 键的形成。高度功能化的药效团和肽也是适用的。
• Silyl-Substituted Amino Acids:  New Routes to the Construction of Selectively Functionalized Peptidomimetics
  作者：Haizhou Sun、Kevin D. Moeller

  DOI：10.1021/ol025776e

  日期：2002.5.1

  [reaction: see text]. Silylated amino acids have been incorporated into peptides and then converted into N-acyliminium ions with the use of an anodic oxidation reaction. The result is a method for selectively incorporating conformational constraints or external nucleophiles within the peptide.

  [反应：请参见文字]。甲硅烷基化的氨基酸已被掺入肽中，然后利用阳极氧化反应转化为N-酰基亚胺离子。结果是一种在肽内选择性掺入构象限制或外部亲核试剂的方法。
• Building Addressable Libraries: Site-Selective Formation of an <i>N</i>-Acyliminium Ion Intermediate
  作者：David Kesselring、Karl Maurer、Kevin D. Moeller

  DOI：10.1021/ol8007827

  日期：2008.6.1

  reactive N-acyliminium ion intermediates on a microelectrode array has been developed. The route capitalizes on the use of an electroauxiliary for building a methoxylated amino acid substrate, and then the electrochemical generation and solution phase confinement of acid in order to form the N-acyliminium ion. Keys to this strategy were the stability of an N-alpha-methoxyalkyl amide to basic reaction conditions

  已经开发了在微电极阵列上选择性地产生反应性N-酰基亚胺离子中间体的策略。该路线利用了使用电助剂来构建甲氧基化的氨基酸底物，然后电化学生成酸并限制溶液的酸相以形成N-酰亚胺离子。该策略的关键是N-α-甲氧基烷基酰胺对碱性反应条件的稳定性以及以位点选择方式进行微电极阵列反应的电酸条件的一般性。
• Novel Isomerization Reaction of <i>N</i>,<i>N</i>-Dimethyl-α-(methoxycarbonyl)-4-substituted- benzylammonium <i>N</i>-Methylides
  作者：Chen Zhang、Hiroto Ito、Yasuhiro Maeda、Naohiro Shirai、Shin-ichi Ikeda、Yoshiro Sato

  DOI：10.1021/jo981729h

  日期：1999.1.1

  Fluoride ion-induced desilylation of N,N-dimethyl-N-[(trimethylsilyl)methyl]-alpha-(methoxycarbonyl)- 4-substituted benzylammonium salts (7) gave two Stevens rearrangement products: methyl 3-(dimethylamino)-2-(4-substituted phenyl)propionates (13) from N-methylides 8, and methyl 3-(dimethylamino)-3-(4-substituted phenyl)propionates (15) from N-benzylides 10. Additional Stevens rearrangement products, methyl 2-(dimethylamino)-3-(4-substituted phenyl)propionates (16), were competitively formed from ylides 12 when the cesium fluoride used was not predried. The mechanism of the isomerization from methylides 8, which was initially generated, to 10 and 12 is discussed.