(1'S,2'S,5'S)-ethyl 2-[(2'-trimethylsiloxypinylidene)amino]acetate

• 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: (1'S,2'S,5'S)-ethyl 2-[(2'-trimethylsiloxypinylidene)amino]acetate
• 英文别名: ethyl 2-[[(1S,2S,5S)-2,6,6-trimethyl-2-trimethylsilyloxy-3-bicyclo[3.1.1]heptanylidene]amino]acetate
• 化学式: C₁₇H₃₁NO₃Si
• 分子量: 325.524
• InChiKey: POJHMQKYWLBQHA-DCGLDWPTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.67
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  47.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1'S,2'S,5'S)-ethyl 2-[(2'-trimethylsiloxypinylidene)amino]acetate 在 偶氮二异丁腈 、 三正丁基氢锡 、 lithium hexamethyldisilazane 作用下， 以 四氢呋喃 、 甲苯 为溶剂， 反应 6.5h， 生成 (1'S,2'S,5'S,2S)-ethyl 2-[(2'-trimethylsiloxypinylidene)amino]-3,3-difluoropropano-1-ate
  参考文献：
  名称：

  Efficient synthesis of an optically pure β-bromo-β,β-difluoroalanine derivative, a general precursor for β,β-difluoroamino acids

  摘要：

  A highly efficient enantioselective preparation of a beta -bromo-beta,beta -difluoroalanine derivative, a promising general precursor for optically active beta,beta -difluoroamino acids, is described. Alkylation of the hydroxypinanone glycinate Schiff base 2a with CF2Br2 resulted in the production of undesired dehydrobrominated product 4a promoted by the lithium alkoxide moiety on the hydroxypinanone chiral auxiliary. Dehydrobromination was prevented by protection of the hydroxyl group on the chiral auxiliary. Utilization of TMSOTf resulted in production of (S,S,S,S)-3b as the sole diastereomer without dehydrobromination. Further transformations of (S,S,S,S)-3b to other optically active beta,beta -difluoroamino acids were demonstrated. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00237-3
• 作为产物：
  描述：

  三甲基氯硅烷 、 (1S,2S,5S)-乙基[(2-羟基蒎烷-3-基烯)氨基]乙酸酯 在 咪唑 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 以92%的产率得到(1'S,2'S,5'S)-ethyl 2-[(2'-trimethylsiloxypinylidene)amino]acetate
  参考文献：
  名称：

  Efficient synthesis of an optically pure β-bromo-β,β-difluoroalanine derivative, a general precursor for β,β-difluoroamino acids

  摘要：

  A highly efficient enantioselective preparation of a beta -bromo-beta,beta -difluoroalanine derivative, a promising general precursor for optically active beta,beta -difluoroamino acids, is described. Alkylation of the hydroxypinanone glycinate Schiff base 2a with CF2Br2 resulted in the production of undesired dehydrobrominated product 4a promoted by the lithium alkoxide moiety on the hydroxypinanone chiral auxiliary. Dehydrobromination was prevented by protection of the hydroxyl group on the chiral auxiliary. Utilization of TMSOTf resulted in production of (S,S,S,S)-3b as the sole diastereomer without dehydrobromination. Further transformations of (S,S,S,S)-3b to other optically active beta,beta -difluoroamino acids were demonstrated. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00237-3

文献信息

• 3-Fluoro- and 3,3-Difluoro-3,4-dideoxy-KRN7000 Analogues as New Potent Immunostimulator Agents: Total Synthesis and Biological Evaluation in Human Invariant Natural Killer T Cells and Mice
  作者：Julie Hunault、Mette Diswall、Jean-Cédric Frison、Virginie Blot、Jézabel Rocher、Séverine Marionneau-Lambot、Thibauld Oullier、Jean-Yves Douillard、Stéphane Guillarme、Christine Saluzzo、Gilles Dujardin、Denis Jacquemin、Jérôme Graton、Jean-Yves Le Questel、Michel Evain、Jacques Lebreton、Didier Dubreuil、Jacques Le Pendu、Muriel Pipelier

  DOI：10.1021/jm201368m

  日期：2012.2.9

  We propose here the synthesis and biological evaluation of 0 3,4-dideoxy-GalCer derivatives. The absence of the 3- and 4-hydroxyls on the sphingoid base is combined with the introduction of mono or difluoro substituent at C3 (analogues 8 and 9, respectively) to evaluate their effect on the stability of the ternary CD1d/GalCer/TCR complex which strongly modulate the immune responses. Biological evaluations were performed in vitro on human cells and in vivo in mice and results discussed with support of modeling studies. The fluoro 3,4-dideoxy-GalCer analogues appears as partial agonists compared to KRN7000 for iNKT cell activation, inducing T(H)1 or T(H)2 biases that strongly depend of the mode of antigen presentation, including human vs mouse differences. We evidenced that if a sole fluorine atom is not able to balance the loss of the 3-OH, the presence of a difluorine group at C3 of the sphingosine can significantly restore human iNKT activation.
• Efficient synthesis of an optically pure β-bromo-β,β-difluoroalanine derivative, a general precursor for β,β-difluoroamino acids
  作者：Toshimasa Katagiri、Michiharu Handa、Yasuhisa Matsukawa、J.S. Dileep Kumar、Kenji Uneyama

  DOI：10.1016/s0957-4166(01)00237-3

  日期：2001.6

  A highly efficient enantioselective preparation of a beta -bromo-beta,beta -difluoroalanine derivative, a promising general precursor for optically active beta,beta -difluoroamino acids, is described. Alkylation of the hydroxypinanone glycinate Schiff base 2a with CF2Br2 resulted in the production of undesired dehydrobrominated product 4a promoted by the lithium alkoxide moiety on the hydroxypinanone chiral auxiliary. Dehydrobromination was prevented by protection of the hydroxyl group on the chiral auxiliary. Utilization of TMSOTf resulted in production of (S,S,S,S)-3b as the sole diastereomer without dehydrobromination. Further transformations of (S,S,S,S)-3b to other optically active beta,beta -difluoroamino acids were demonstrated. (C) 2001 Elsevier Science Ltd. All rights reserved.