(2S)-2-acetoxy-3,3-dimethylbutanoic acid | 84621-74-9

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 英文名称: (2S)-2-acetoxy-3,3-dimethylbutanoic acid
• 英文别名: (2S)-2-acetyloxy-3,3-dimethylbutanoic acid
• CAS: 84621-74-9
• 化学式: C₈H₁₄O₄
• 分子量: 174.197
• InChiKey: PCYORGQXWYECJK-ZCFIWIBFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (2S)-2-acetoxy-3,3-dimethylbutanoic acid 在 titanium(IV) tetrabutoxide 、 氯化亚砜 、 一水合肼 、 N,N-二甲基甲酰胺 作用下， 以 乙醚 、 乙醇 、 二氯甲烷 为溶剂， 反应 17.36h， 生成
  参考文献：
  名称：

  Atkinson, Robert S.; Ayscough, Andrew P.; Gattrell, Journal of the Chemical Society. Perkin transactions I, 1998, # 17, p. 2783 - 2793

  摘要：

  DOI：
• 作为产物：
  描述：

  特戊醛 在 盐酸 、 硫酸 作用下， 以 水 为溶剂， 反应 14.5h， 生成 (2S)-2-acetoxy-3,3-dimethylbutanoic acid
  参考文献：
  名称：

  通过杂环中间体，XVI进行不对称合成。通过烷基化C-6手性取代的3,6-二氢-3-苯基-2 H -1,4-恶嗪-2-酮对映体合成α-烷基-α-苯基甘氨酸

  摘要：

  从DL-苯基甘氨酸和（S）-2-羟基链烷酸4开始，构建了3,6-二氢-3-苯基-2 H -1,4-恶嗪-2-酮3，它们的内环中心为C-6的手性。阴离子10的3与烷基卤化物反应，在C-3具有良好的化学产率，并用50至95％以上的德（不对称诱导）。在加合物11的水解过程中，释放出2-羟基链烷酸4和旋光的（S）-α-烷基-α-苯基甘氨酸14。

  DOI：

  10.1002/jlac.198219821105

文献信息

• Electrogenerated chiral building blocks for diastereoselective amidoalkylation reactions
  作者：P Brungs、K Danielmeier、J Jakobi、C Nothhelfer、A Stahl、A Zietlow、E Steckhan

  DOI：10.1051/jcp/1996930575

  日期：——

  Three different electrochemical methods have been applied for the synthesis of chiral building blocks for diastereoselective amidoalkylation reactions. These are A. the direct anodic α-methoxylation of amides and carbamates; B. anodic methoxylative decarboxylation of α-amino acid derivatives (Hofer-Moest reaction) C. indirect NaCl mediated anodic α-methoxylation of α-amino acid derivatives. The application of these building blocks for the synthesis of enantiomerically pure α-amino acids, dichiral 1,2-amino alcohols and chiral 1,3-diamines is described.

  已经应用了三种不同的电化学方法来合成用于二分立体选择性氨基烷基化反应的手性构建块。这些方法包括：A. 酰胺和碳酸酯的直接阳极α-甲氧基化；B. α-氨基酸衍生物的阳极甲氧基化脱羧（Hofer-Moest反应）C. 间接NaCl介导的α-氨基酸衍生物的阳极α-甲氧基化。描述了这些构建块在合成手性纯α-氨基酸、二分手性1,2-氨基醇和手性1,3-二胺中的应用。
• Synthesis of 4,4′-biquinazoline alcohols as chiral catalysts in enantioselective alkynylation of aldehydes with phenyl acetylene
  作者：Mustafa Catir、Murat Cakici、Semistan Karabuga、Sabri Ulukanli、Ertan Şahin、Hamdullah Kilic

  DOI：10.1016/j.tetasy.2009.12.002

  日期：2009.12

  propargylic alcohols are important chiral-building blocks in asymmetric synthesis, while the asymmetric addition of a terminal alkyne to an aldehyde is one of the most important procedures to prepare these chiral-building blocks. In this work, a family of chiral 4,4′-biquinazoline alcohols has been conveniently prepared from the easily accessible (S)-2-acetoxycarboxylic acid chlorides by reaction sequences

  光学活性的炔丙醇是不对称合成中的重要手性结构单元，而末端炔烃不对称加成到醛中是制备这些手性结构单元的最重要方法之一。在这项工作中，通过反应顺序，从缩合反应开始，然后进行关键的合成步骤，包括氯化，镍（0），这是很容易从易于获得的（S）-2-乙酰氧基羧酸氯化物制备的手性4,4'-联喹唑啉醇家族介导的均偶联和脱保护作用，此外还考虑了将苯基乙炔对醛进行对映选择性加成时可能的配体。这些手性配体可以与Ti（O i Pr）4结合然后用于催化由乙炔与二乙基锌反应原位生成的乙炔锌不对称加成到醛中。在这项研究中获得的最佳对映体过量为75％。
• Reagent- and chelation-controlled diastereoselective aziridination of electron-rich alkenes by 3-acetoxyamino-2-(1-hydroxy-2,2-dimethylprop-1-yl)-quinazolin-4(3H)-one
  作者：Robert S. Atkinson、William T. Gattrell、Andrew P. Ayscough、Tony M. Raynham

  DOI：10.1039/cc9960001935

  日期：——

  In the presence of titanium (IV)tert-butoxide, the title 3-acetoxyaminoquinazolinone aziridinates styrene, butadiene and indene completely diastereoselectively; the absolute configuration of the styrene-derived aziridine 6a is proven by X-ray crystallography and is consistent with a transition state model involving chelation control by titanium.

  在四氟化钛(IV)叔丁醇的存在下，标题中的3-乙氧基氨基喹唑啉酮能够完全的二氟选择性地对苯乙烯、丁二烯和茚进行腈化反应；通过X射线晶体学证明了苯乙烯衍生的腈化物6a的绝对构型，并且与涉及钛的配位控制的过渡态模型一致。
• Discovery of <i>N</i>-(3-Carbamoyl-5,5,7,7-tetramethyl-5,7-dihydro-4<i>H</i>-thieno[2,3-<i>c</i>]pyran-2-yl)-l<i>H</i>-pyrazole-5-carboxamide (GLPG1837), a Novel Potentiator Which Can Open Class III Mutant Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) Channels to a High Extent
  作者：Steven E. Van der Plas、Hans Kelgtermans、Tom De Munck、Sébastien L. X. Martina、Sébastien Dropsit、Evelyne Quinton、Ann De Blieck、Caroline Joannesse、Linda Tomaskovic、Mia Jans、Thierry Christophe、Ellen van der Aar、Monica Borgonovi、Luc Nelles、Maarten Gees、Pieter Stouten、Jan Van Der Schueren、Oscar Mammoliti、Katja Conrath、Martin Andrews

  DOI：10.1021/acs.jmedchem.7b01288

  日期：2018.2.22

  Cystic fibrosis (CF) is caused by mutations in the gene for the cystic fibrosis transmembrane conductance regulator (CFTR). With the discovery of Ivacaftor and Orkambi, it has been shown that CFTR function can be partially restored by administering one or more small molecules. These molecules aim at either enhancing the amount of CFTR on the cell surface (correctors) or at improving the gating function of the CFTR channel (potentiators). Here we describe the discovery of a novel potentiator GLPG1837, which shows enhanced efficacy on CFTR mutants harboring class III mutations compared to Ivacaftor, the first marketed potentiator. The optimization of potency, efficacy, and pharmacokinetic profile will be described.
• Peptidomimetic Inhibitors of the Human Cytomegalovirus Protease
  作者：William Ogilvie、Murray Bailey、Marc-André Poupart、Abraham、Amit Bhavsar、Pierre Bonneau、Josée Bordeleau、Yves Bousquet、Catherine Chabot、Jean-Simon Duceppe、Gulrez Fazal、Sylvie Goulet、Chantal Grand-Maître、Ingrid Guse、Ted Halmos、Pierre Lavallée、Michael Leach、Eric Malenfant、Jeff O'Meara、Raymond Plante、Céline Plouffe、Martin Poirier、François Soucy、Christiane Yoakim、Robert Déziel

  DOI：10.1021/jm970104t

  日期：1997.12.1

  The development of peptidomimetic inhibitors of the human cytomegalovirus (HCMV) :protease showing sub-micromolar potency in an enzymatic assay is described. Selective substitution of the amino acid residues of these inhibitors led to the identification of tripeptide inhibitors showing improvements in inhibitor potency cf 27-fold relative to inhibitor 39 based upon the natural tetrapeptide sequence. Small side chains at P-1 were well tolerated by this enzyme, a fact consistent with previous observations. The S-2 binding pocket of HCMV protease was very permissive, tolerating lipophilic and basic residues. The substitutions tried at P-3 indicated that a small increase in inhibitor potency could be realized by the substitution of a tert-leucine residue for valine. Substitutions of the N-terminal capping group did not significantly affect inhibitor potency. Pentafluoroethyl ketones, alpha,alpha-difluoro-beta-keto amides, phosphonates and a-keto amides were all effective substitutions for the activated carbonyl component and gave inhibitors which were selective for HCMV protease. A slight increase in potency was observed by lengthening the P-1' residue of the alpha-keto amide series of inhibitors. This position also tolerated a variety of groups making this a potential site for future modifications which could modulate the physicochemical properties of these molecules.