4(R)-methyl-3-(1-oxo-3-methylbutyl)-5(S)-phenyl-2-oxazolidinone | 107599-99-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑烷类
• 英文名称: 4(R)-methyl-3-(1-oxo-3-methylbutyl)-5(S)-phenyl-2-oxazolidinone
• 英文别名: (4R)-3-(3-Methylbutanoyl)-4alpha-methyl-5alpha-phenyloxazolidin-2-one；(4R,5S)-4-methyl-3-(3-methylbutanoyl)-5-phenyl-1,3-oxazolidin-2-one
• CAS: 107599-99-5
• 化学式: C₁₅H₁₉NO₃
• 分子量: 261.321
• InChiKey: DRVYMRBXCGWILR-BXUZGUMPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  19
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  4(R)-methyl-3-(1-oxo-3-methylbutyl)-5(S)-phenyl-2-oxazolidinone 在 ethandithiol 、 ruthenium trichloride 、 diethylphosphoryl cyanide 、 (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate 、 过碘酸 、 N,N-二异丙基乙胺 、 乙酰氯 、 三氟乙酸 作用下， 以 甲醇 、 四氯化碳 、 二氯甲烷 、 水 、 乙腈 为溶剂， 反应 35.25h， 生成 (2R,3R,4R,5S)-6-Cyclohexyl-3,4-dihydroxy-5-{(S)-3-(1H-imidazol-4-yl)-2-[2-(naphthalen-1-yloxy)-acetylamino]-propionylamino}-2-isopropyl-hexanoic acid {(1S,2S)-2-methyl-1-[(pyridin-2-ylmethyl)-carbamoyl]-butyl}-amide
  参考文献：
  名称：

  Inhibitors of the protease from human immunodeficiency virus: design and modeling of a compound containing a dihydroxyethylene isostere insert with high binding affinity and effective antiviral activity

  摘要：

  The peptidomimetic template and the dihydroxyethylene isostere insert that were applied successfully to the design of renin inhibitors have been extended to the related protease from human immunodeficiency virus (HIV). The present report describes the structure-activity study leading to the identification of an inhibitor with a K(i) of < 1 nM for the HIV type-1 protease (compound II). This compound, containing a diol insert, is highly effective in blocking polyprotein processing in in vitro cell culture assays. Results obtained from kinetic analysis, studies of the stereochemistry of the insert, and modeling have led to insights as to the requisites involved in the active site-inhibitor interaction.

  DOI：

  10.1021/jm00112a005
• 作为产物：
  描述：

  (4R,5S)-(+)-3-[(2R)-2-isopropyl-5-methyl-1-oxohex-5-en-1-yl]-4-methyl-5-phenyl-2-oxazolidinone 在 lithium hydroxide 、 双氧水 作用下， 以 四氢呋喃 、 正己烷 、 水 为溶剂， 反应 19.0h， 生成 4(R)-methyl-3-(1-oxo-3-methylbutyl)-5(S)-phenyl-2-oxazolidinone
  参考文献：
  名称：

  Asymmetric synthesis and Lewis acid mediated type II carbonyl ene cyclisations of (R)-2-isopropyl-5-methylhex-5-enal

  摘要：

  The asymmetric synthesis of (R)-2-isopropyl-5-methylhex-5-enal in 98% ee is described. It was discovered that the key alkylation step employing an Evans chiral auxiliary and 3-methylbut-3-en-1-yl trifluoromethanesulphonate as the alkylating agent led to significant competing O-alkylation, a phenomenon not previously reported. Type II carbonyl ene cyclisation of the aldehyde with a range of Lewis acids led to either the (R,R)- or (R,S)-5-methylidenecyclohexanols without concurrent racemisation of the alpha stereogenic centre of the aldehyde. Conditions for effecting the easy racemisation of a model enantiomerically pure aldehyde, (S)-2-methylbutanal, were developed. In an effort to secure a dynamic kinetic resolution procedure, these conditions were applied to (R)-2-isopropyl-5-methylhex-5-enal. However, a competing and dominant Prins cyclisation occurred instead leading to a mixture of all possible cycloadducts, all of which were obtained in 98% ee. Any unreacted aldehyde was found to be enantiomerically pure. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00316-5

文献信息

• Sensing Remote Chirality: Stereochemical Determination of β-, γ-, and δ-Chiral Carboxylic Acids
  作者：Marina Tanasova、Mercy Anyika、Babak Borhan

  DOI：10.1002/anie.201410371

  日期：2015.3.27

  nonfunctionalizable stereocenters is a challenging task. Presented is a solution in which appropriately substituted bis(porphyrin) tweezers are used. Complexation of a suitably derivatized β‐, γ‐, or δ‐chiral carboxylic acid to the tweezer induces a predictable helicity of the bis(porphyrin), which is detected as a bisignate Cotton Effect (ECCD). The sign of the ECCD curve is correlated with the absolute

  确定带有远程不可官能化立体中心的小分子的绝对立体化学是一项艰巨的任务。提出了一种使用适当取代的双（卟啉）镊子的溶液。适当地衍生化的β-，γ-或δ-手性羧酸与镊子的络合可诱导双卟啉的可预测螺旋度，这被检测为二元棉花效应（ECCD）。ECCD曲线的符号基于派生的工作助记符以可预测的方式与基材的绝对立体化学相关。
• Novel gamma-lactams as beta-secretase inhibitors
  申请人：Thompson A. Lorin

  公开号：US20060046984A1

  公开（公告）日：2006-03-02

  There is provided a series of novel substituted gamma-lactams of Formula (I) or a stereoisomer; or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 4 , R 5 and R 6 as defined herein, their pharmaceutical compositions and methods of use. These novel compounds inhibit the processing of amyloid precursor protein (APP) by β-secretase and, more specifically, inhibit the production of Aβ-peptide. The present disclosure is directed to compounds useful in the treatment of neurological disorders related to β-amyloid production, such as Alzheimer's disease and other conditions affected by anti-amyloid activity.

  提供了一系列新型取代的γ-内酰胺，化学式为(I)或其立体异构体；或其药用盐，其中R1、R2、R4、R5和R6如本文所定义，它们的药用组合物和使用方法。这些新型化合物抑制β-分泌酶对淀粉样前体蛋白（APP）的加工，更具体地抑制Aβ肽的产生。本公开涉及对β-淀粉样蛋白产生相关的神经系统疾病的治疗有用的化合物，如阿尔茨海默病和其他受抗淀粉样活性影响的疾病。
• Conformational Preference in Bis(porphyrin) Tweezer Complexes: A Versatile Chirality Sensor for α-Chiral Carboxylic Acids
  作者：Marina Tanasova、Babak Borhan

  DOI：10.1002/ejoc.201200147

  日期：2012.6

  determinant of binding conformation. Experimental results indicate that a balance between linker flexibility and rigidity could yield an optimum porphyrin tweezer that stabilizes a common conformation for all bound chiral guests. This leads to a more simplified approach to absolute stereochemical determination of asymmetry for small organic molecules. This was demonstrated by the use of a C3-linked zincated

  金属化卟啉镊子已表现出非凡的能力，可以作为许多不同类别有机分子的绝对立体化学报告者。然而，结合的灵活性可能导致不同激子耦合圆二色性 (ECCD) 活性构象的集合，这可能导致可变的结果。发现接头灵活性是结合构象的关键决定因素。实验结果表明，接头柔韧性和刚性之间的平衡可以产生最佳的卟啉镊子，稳定所有结合手性客体的共同构象。这导致了一种更简单的方法来确定小有机分子的不对称性的绝对立体化学。
• Renin inhibitors. Design of angiotensinogen transition-state analogs containing novel (2R,3R,4R,5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid
  作者：Suvit Thaisrivongs、Donald T. Pals、Lisa T. Kroll、Steve R. Turner、Fu Son Han

  DOI：10.1021/jm00389a004

  日期：1987.6

  5S)-5-amino-3,4-dihydroxy-2-isopropyl-7-methyloctanoic acid residue at the scissile site are shown to be potent inhibitors of human plasma renin. The glycol moiety in this novel acid, dihydroxyethylene isostere, is suggested to act as a transition-state analogue and mimics the tetrahedral intermediate formed during the enzyme-catalyzed hydrolysis of the peptidic bond.

  2（R）-[5（R）-[1（S）-[（叔丁氧羰基氨基）氨基] -3-甲基丁基] -2,2-二甲基-4（R-二氧戊环）-的高立体选择性合成描述了3-甲基丁酸。这是一种适当保护的羧酸，可用作制备肾素抑制肽的中间体。血管紧张素原类似物如肽IX和X在易裂位点含有二肽等排物（2R，3R，4R，5S）-5-氨基-3,4-二羟基-2-异丙基-7-甲基辛酸残基人血浆肾素的有效抑制剂。该新型酸二羟基乙烯等排物中的二醇部分被建议充当过渡态类似物，并模仿在酶催化的肽键水解过程中形成的四面体中间体。
• Novel renin inhibiting peptides having a dihydroxyethylene isostere transition state insert
  申请人：THE UPJOHN COMPANY

  公开号：EP0237202A2

  公开（公告）日：1987-09-16

  The present invention provides novel renin-inhibiting peptides of the formula X-A6-B7-C8-D9-E10-F11-G12-H13-I14-Z, wherein the E10-F11 moiety is a dihydroxyethylene isostere, X and Z are terminal groups, and the remaining variables are absent or are amino acid residues. Such inhibitors are useful for the control of hypertension.

  本发明提供了式X-A6-B7-C8-D9-E10-F11-G12-H13-I14-Z的新型肾素抑制肽，其中E10-F11分子是二羟基乙烯异构体，X和Z是末端基团，其余变量不存在或为氨基酸残基。 这种抑制剂可用于控制高血压。