4,4-dimethyl-tetrahydro-pyran-2-one | 22791-80-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 4,4-dimethyl-tetrahydro-pyran-2-one
• 英文别名: 4,4-dimethyltetrahydro-2H-pyran-2-one；5-hydroxy-3,3-dimethylpentanoic acid lactone；3,3-dimethyl-δ-valerolacton；2H-Pyran-2-one, tetrahydro-4,4-dimethyl-；4,4-dimethyloxan-2-one
• CAS: 22791-80-6
• 化学式: C₇H₁₂O₂
• 分子量: 128.171
• InChiKey: QBEOGDDXOQMTPC-UHFFFAOYSA-N

物化性质

• 熔点：
  29-30 °C
• 沸点：
  234-235 °C
• 密度：
  0.967±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

安全信息

• 海关编码：
  2932999099

反应信息

• 作为反应物：
  描述：

  4,4-dimethyl-tetrahydro-pyran-2-one 在 一水合肼 作用下， 以 甲醇 、 水 为溶剂， 反应 5.0h， 以82%的产率得到5-hydroxy-3,3-dimethylpentanoyl hydrazide
  参考文献：
  名称：

  Discovery of a Flexible Triazolylbutanoic Acid as a Highly Potent Uric Acid Transporter 1 (URAT1) Inhibitor

  摘要：

  为了系统地探索和理解基于lesinurad的命中化合物（1c）的结构-活性关系（SAR），该化合物是通过将lesinurad中的S原子替换为CH2得到的，设计并合成了18个化合物（1a–1r），并对其进行了体外URAT1抑制活性测试。SAR探索发现了一个高效的柔性URAT1抑制剂1q，其活性比母体lesinurad高31倍（对于人URAT1的IC50值，1q为0.23 μM，而lesinurad为7.18 μM）。本研究发现了一种柔性分子骨架，如1q所示，这可能作为进一步开发高效URAT1抑制剂的有前景的原型骨架，并且表明lesinurad中的S原子对其URAT1抑制活性并非必需。

  DOI：

  10.3390/molecules21111543
• 作为产物：
  描述：

  4,4-二甲基-2,6-二氧代哌啶-3,5-二甲腈 在 sodium tetrahydroborate 、 硫酸 、 水 、 乙酸酐 作用下， 以 四氢呋喃 为溶剂， 反应 90.0h， 生成 4,4-dimethyl-tetrahydro-pyran-2-one
  参考文献：
  名称：

  The development of a new class of inhibitors for betaine-homocysteine S-methyltransferase

  摘要：

  Betaine-homocysteine S-methyltransferase (BHMT) is an important zinc-dependent methyltransferase that uses betaine as the methyl donor for the remethylation of homocysteine to form methionine. In the liver, BHMT performs to half of the homocysteine remethylation. In this study, we systematically investigated the tolerance of the enzyme for modifications at the "homocysteine" part of the previously reported potent inhibitor (R,S)-5-(3-amino-3-carboxy-propylsulfanyl)-pentanoic acid (1). In the new compounds, which are S-alkylated homocysteine derivatives, we replaced the carboxylic group in the "homocysteine" part of inhibitor 1 with different isosteric moieties (tetrazole and oxadiazolone); we suppressed the carboxylic negative charge by amidations; we enhanced acidity by replacing the carboxylate with phosphonic or phosphinic acids; and we introduced pyrrolidine steric constraints. Some of these compounds display high affinity toward human BHMT and may be useful for further pharmacological studies of this enzyme. Although none of the new compounds were more potent inhibitors than the reference inhibitor 1, this study helped to completely define the structural requirements of the active site of BHMT and revealed the remarkable selectivity of the enzyme for homocysteine. (C) 2013 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2013.04.039

文献信息

• Transformation of 5-Hydroxy- to (5-Chloropentanoyl)amino Derivatives under ‘Direct Amide Cyclization’ Conditions
  作者：Boyan Iliev、Sanjiv Verma、Anthony Linden、Heinz Heimgartner

  DOI：10.1002/hlca.200690038

  日期：2006.2

  The application of the ‘direct amide cyclization’ conditions to the linear δ-hydroxy diamide 11 is described (Scheme 3). Instead of the cyclization to the expected nine-membered cyclodepsipeptide, only the chloro acid 12 was obtained. Its formation could be explained by consecutive formation of the 1,3-oxazol-5(4H)-one 16 and the six-membered imino lactone 17 as intermediates (Scheme 4). The spontaneous

  描述了将“直接酰胺环化”条件应用于线性δ-羟基二酰胺11（方案3）。代替环化成预期的九元环二肽，仅获得了氯酸12。它的形成可以通过作为中间体的1,3-恶唑-5（4 H）-one 16和六元亚氨基内酯17的连续形成来解释（方案4）。后者的自发异构化以良好的收率得到12。
• Catalytic Asymmetric Synthesis of Cyclohexanes by Hydrogen Borrowing Annulations
  作者：Roly J. Armstrong、Wasim M. Akhtar、Tom A. Young、Fernanda Duarte、Timothy J. Donohoe

  DOI：10.1002/anie.201907514

  日期：2019.9.2

  Hydrogen borrowing catalysis serves as a powerful alternative to enolate alkylation, enabling the direct coupling of ketones with unactivated alcohols. However, to date, methods that enable control over the absolute stereochemical outcome of such a process have remained elusive. Here we report a catalytic asymmetric method for the synthesis of enantioenriched cyclohexanes from 1,5‐diols via hydrogen

  氢借位催化是烯醇化烷基化的有力替代方法，可将酮与未活化的醇直接偶联。然而，迄今为止，仍无法控制这种方法的绝对立体化学结果的方法。在这里，我们报告了一种通过氢借位催化从1,5-二醇合成对映体富集的环己烷的催化不对称方法。该反应是通过添加手性铱（I）络合物来介导的，该络合物能够在该过程中赋予高水平的对映选择性。已经制备了一系列对映体富集的环己烷，并且通过结合实验和DFT研究探索了对映体诱导的模式。
• Copper-catalyzed enantioselective alkene carboetherification for the synthesis of saturated six-membered cyclic ethers
  作者：Ilyas A. Berhane、Ameya S. Burde、Jonathan J. Kennedy-Ellis、Eva Zurek、Sherry R. Chemler

  DOI：10.1039/d1cc03515k

  日期：——

  The enantioselective copper-catalyzed oxidative coupling of alkenols with styrenes for the construction of dihydropyrans, isochromans, pyrans and morpholines is reported. A concise formal synthesis of a σ1 receptor ligand using this alkene carboetherification methodology was demonstrated. Ligand, solvent and base all impact reaction efficiency. DFT transition state calculations are presented.

  报道了烯醇与苯乙烯的对映选择性铜催化氧化偶联，用于构建二氢吡喃、异色满、吡喃和吗啉。证明了使用这种烯烃碳醚化方法的 σ 1受体配体的简明形式合成。配体、溶剂和碱都会影响反应效率。给出了 DFT 过渡态计算。
• [EN] PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE COMPOUNDS AND THEIR USE IN THE TREATMENT OF MEDICAL DISORDERS<br/>[FR] COMPOSÉS DE PYRAZOLO[1,5-A]PYRIMIDINYL CARBOXAMIDE ET LEUR UTILISATION DANS LE TRAITEMENT DE TROUBLES MÉDICAUX
  申请人：LYSOSOMAL THERAPEUTICS INC

  公开号：WO2017176960A1

  公开（公告）日：2017-10-12

  The invention provides substituted pyrazolo[1,5-a]pyrimidinyl carboxamide and related organic compounds, compositions containing such compounds, medical kits, and methods for using such compounds and compositions to treat medical disorders, e.g., Gaucher disease, Parkinson's disease, Lewy body disease, dementia, or multiple system atrophy, in a patient. Exemplary substituted pyrazolo[1,5-a]pyrimidinyl carboxamide compounds described herein include 2-heterocyclyl-4-alkyl-pyrazolo[1,5-a]pyrirnidine-3-carboxarnide compounds and variants thereof.

  本发明提供了取代的吡唑[1,5-a]嘧啶基甲酰胺及其相关有机化合物，包含此类化合物的组合物，医疗包，以及使用此类化合物和组合物治疗医疗障碍的方法，例如，戈谢病，帕金森病，路易体病，痴呆症或多系统萎缩症。所述的代表性的取代吡唑[1,5-a]嘧啶基甲酰胺化合物包括2-杂环基-4-烷基-吡唑[1,5-a]嘧啶-3-甲酰胺化合物及其变体。
• INTEGRIN INHIBITORS
  申请人：Morphic Therapeutic, Inc.

  公开号：EP3617206A1

  公开（公告）日：2020-03-04

  Disclosed are small molecule inhibitors of αvβ6 integrin, and methods of using them to treat a number of diseases and conditions.

  揭示了αvβ6整合素的小分子抑制剂，以及使用它们治疗多种疾病和症状的方法。