(4S,5R)-4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one

• 分子结构分类: 有机化合物 - 苯类化合物 - 三苯基化合物
• 英文名称: (4S,5R)-4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one
• 英文别名: (4S,5R)-4-(trityloxymethyl)-3-oxa-1-azabicyclo[3.1.0]hexan-2-one
• 化学式: C₂₄H₂₁NO₃
• 分子量: 371.436
• InChiKey: RMJDTIFBZBCISS-QQMHWKEJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  28
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  38.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (4S,5R)-4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one 在 盐酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 18.0h， 生成 IMB-61
  参考文献：
  名称：

  Structure–activity studies of RNA-binding oxazolidinone derivatives

  摘要：

  The structure-activity relationship of a series of oxazolidinones binding to T-box riboswitch antiterminator RNA has been investigated. Oxazolidinones differentially substituted at C-5 were prepared and the ligand-induced fluorescence resonance energy transfer (FRET) changes in FRET-labeled antiterminator model RNA were assayed. Both qualitative and quantitative analysis of the structure-activity relationship indicate that hydrogen bonding and hydrophobic properties play a significant role in ligand binding. (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.05.130
• 作为产物：
  描述：

  (S)-1-(triphenylmethoxy)-3-buten-2-ol 在 吡啶 、 sodium azide 作用下， 以 二氯甲烷 、 水 、 丙酮 为溶剂， 反应 86.0h， 生成 (4S,5R)-4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one
  参考文献：
  名称：

  Synthesis and Stereospecificity of 4,5-Disubstituted Oxazolidinone Ligands Binding to T-box Riboswitch RNA

  摘要：

  The enantiomers and the cis isomers of two previously studied 4,5-disubstituted oxazolidinones have been synthesized, and their binding to the T-box riboswitch antiterminator model RNA has been investigated in detail. Characterization of ligand affinities and binding site localization indicates that there is little stereospecific discrimination for binding antiterminator RNA alone. This binding similarity between enantiomers is likely due to surface binding, which accommodates ligand conformations 1 that result in comparable ligand-antiterminator contacts. These results have significant implications for T-box antiterminator-targeted drug discovery and, in general, for targeting other medicinally relevant RNA that do not present deep binding pockets.

  DOI：

  10.1021/jm2006904

文献信息

• Routes to N-glycinamide oxazolidinone derivatives: The reaction of 4-trityloxymethyl-3-oxa-1-azabicyclo[3.1.0]hexan-2-one with active halides
  作者：Zilong Zheng、Stephen C. Bergmeier

  DOI：10.24820/ark.5550190.p010.812

  日期：——

  N-Glycinamide oxazolidinones are key intermediates for the synthesis of a new class of peptidomimetics. We report, herein, the synthesis of a series of 3,4,5-trisubstituted oxazolidinones with a glycine residue at N-3 of the oxazolidinone ring. Substituents at C-4 and C-5 contain substitution capabilities which are amenable for the introduction of additional peptide chains. The synthesis of the key

  N-甘氨酰胺恶唑烷酮是合成一类新型肽模拟物的关键中间体。我们在此报告了一系列 3,4,5-三取代的恶唑烷酮的合成，在恶唑烷酮环的 N-3 处具有甘氨酸残基。C-4 和 C-5 上的取代基含有取代能力，可用于引入额外的肽链。关键 N-甘氨酰胺恶唑烷酮的合成通过两个反应成为可能；串联氮丙啶开环/恶唑烷酮烷基化，随后通过胺进行稠合内酯开环，产生 N-甘氨酰胺恶唑烷酮。
• RNA drug discovery: Conformational restriction enhances specific modulation of the T-box riboswitch function
  作者：Ian Armstrong、Ali H. Aldhumani、Jia L. Schopis、Fang Fang、Eric Parsons、Chunxi Zeng、Md. Ismail Hossain、Stephen C. Bergmeier、Jennifer V. Hines

  DOI：10.1016/j.bmc.2020.115696

  日期：2020.10

  discovery. The T-box riboswitch is a regulatory RNA mechanism that controls gene expression in Gram-positive bacteria and is an exceptional, novel target for antibacterial drug design. We report the design, synthesis and activity of a series of conformationally restricted oxazolidinone-triazole compounds targeting the highly conserved antiterminator RNA element of the T-box riboswitch. Computational binding

  抗菌药物耐药性是一个全球性的健康问题，需要多种解决方法，包括开发针对新靶点的新抗菌化合物。靶向调控 RNA 是药物发现的一个新兴领域。T-box 核糖开关是一种控制革兰氏阳性菌基因表达的调节性 RNA 机制，是抗菌药物设计的一个特殊的新靶点。我们报告了一系列构象受限的恶唑烷酮-三唑化合物的设计、合成和活性，这些化合物靶向 T-box 核糖开关的高度保守的抗终止子 RNA 元件。与实验得出的 K d相关的计算结合能值表明该系列化合物中对接研究的预测能力。构象限制化合物专门抑制 T-box 核糖开关功能，而不是整体转录。复杂的破坏、计算对接和 RNA 结合特异性数据表明抑制可能是由配体与变构位点结合引起的。这些结果强调了配体亲和力和 RNA 构象结果对于靶向 RNA 药物设计的重要性。
• A Synthesis of Hexahydro-H-oxazolo[3,4-a]pyrazin-3-ones from Fused Aziridines
  作者：Stephen C. Bergmeier、Fang Fang、Iwona Maciagiewicz

  DOI：10.3987/com-15-s(t)24

  日期：——

  The piperazine ring is a common structural component of a large variety of biologically active small molecules. While a number of methods to prepare simple piperazine rings are known, the methods available for the synthesis of fused-ring piperazines are lacking. We report here a method for the synthesis of novel fused-ring piperazines through reaction with fused-ring aziridines followed by a ring closure to form the fused-ring piperazine system. The dependence of the reaction on the stereochemistry of the system has also been studied.
• 4,5-Disubstituted oxazolidinones: High affinity molecular effectors of RNA function
  作者：Rajaneesh Anupam、Abhijit Nayek、Nicholas J. Green、Frank J. Grundy、Tina M. Henkin、John A. Means、Stephen C. Bergmeier、Jennifer V. Hines

  DOI：10.1016/j.bmcl.2008.05.015

  日期：2008.6

  The T box transcription antitermination system is a riboswitch found primarily in Gram-positive bacteria which monitors the aminoacylation of the cognate tRNA and regulates a variety of amino acid-related genes. Novel 4,5-disubstituted oxazolidinones were identified as high affinity RNA molecular effectors that modulate the transcription antitermination function of the T box riboswitch. (C) 2008 Elsevier Ltd. All rights reserved.
• Studies on the ring opening reactions of 3-oxa-1-azabicyclo[3.1.0]hexan-2-ones. Synthesis of aminomethyl oxazolidinones and aziridinyl ureas
  作者：Greggory M. Wells、Travis Dudding、Lee Belding、Jeffery A. Frick、Abhijit Nayek、Junfeng Huang、Steven J. Katz、Stephen C. Bergmeier

  DOI：10.1016/j.tet.2012.03.071

  日期：2012.5

  The reaction of fused ring aziridines, 3-oxa-1-azabicyclo[3.1.0]hexan-2-ones, with amine nucleophiles can provide either an aminomethyl oxazolidinone or an aziridinyl urea. The amine, reaction solvent, and aziridine substitution have been examined with the aid of computational studies to identify reaction conditions that provide a single product. Polar solvents provided only the aminomethyl oxazolidinone products. Formation of aziridinyl ureas required control of aziridine substitution, solvent, and reactant stoichiometry. (C) 2012 Elsevier Ltd. All rights reserved.