O-tert-butyldimethylsilyl-DL-homoserine methyl ester | 1002105-80-7

• 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: O-tert-butyldimethylsilyl-DL-homoserine methyl ester
• 英文别名: methyl 2-amino-4-[(tert-butyldimethylsilyl)oxy]butanoate；Methyl 2-amino-4-[tert-butyl(dimethyl)silyl]oxybutanoate
• CAS: 1002105-80-7
• 化学式: C₁₁H₂₅NO₃Si
• 分子量: 247.41
• InChiKey: IMBMUUZNQXKOBS-UHFFFAOYSA-N

物化性质

• 沸点：
  282.6±25.0 °C(Predicted)
• 密度：
  0.952±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  16
• 可旋转键数：
  7
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  61.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  O-tert-butyldimethylsilyl-DL-homoserine methyl ester 在 N-羟基-7-氮杂苯并三氮唑 、 N,N-二异丙基乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 、 N-[(dimethylamino)-3-oxo-1H-1,2,3-triazolo[4,5-b]pyridin-1-yl-methylene]-N-methylmethanaminium hexafluorophosphate 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 methyl 2-(5-fluoro-1H-indol-2-yl)-5,6-dihydro-4H-1,3-oxazine-4-carboxylate
  参考文献：
  名称：

  Potent, Novel in Vitro Inhibitors of the Pseudomonas aeruginosa Deacetylase LpxC

  摘要：

  Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 muM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.

  DOI：

  10.1021/jm010579r
• 作为产物：
  描述：

  叔丁基二甲基氯硅烷 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 、 甲醇 、 甲苯 、 乙腈 为溶剂， 反应 32.0h， 生成 O-tert-butyldimethylsilyl-DL-homoserine methyl ester
  参考文献：
  名称：

  WO2019173327A5

  摘要：

  公开号：

  WO2019173327A5

文献信息

• Enantioselective TADMAP-Catalyzed Carboxyl Migration Reactions for the Synthesis of Stereogenic Quaternary Carbon
  作者：Scott A. Shaw、Pedro Aleman、Justin Christy、Jeff W. Kampf、Porino Va、Edwin Vedejs

  DOI：10.1021/ja056150x

  日期：2006.1.1

  efficient and are used to prepare chiral lactams (23) and lactones (30) containing a quaternary asymmetric carbon. TADMAP-catalyzed carboxyl migrations in the indole series are relatively slow and proceed with inconsistent enantioselectivity. Modeling studies (B3LYP/6-31G*) have been used in qualitative correlations of catalyst conformation, reactivity, and enantioselectivity.

  手性亲核催化剂 TADMAP [1, 3-(2,2,2-三苯基-1-乙酰氧基乙基)-4-(二甲氨基)吡啶]已由 3-锂硫-4-(二甲氨基)吡啶 (5) 和三苯乙醛 (3)，然后进行酰化和拆分。TADMAP 催化恶唑基、呋喃基和苯并呋喃基烯醇碳酸酯的羧基迁移，具有良好到极好的对映选择水平。恶唑反应特别有效，用于制备含有季不对称碳的手性内酰胺 (23) 和内酯 (30)。吲哚系列中 TADMAP 催化的羧基迁移相对较慢，并且具有不一致的对映选择性。建模研究 (B3LYP/6-31G*) 已用于定性关联催化剂构象、反应性和对映选择性。
• Stereoselective synthesis of 2,4,5-trisubstituted piperidines by carbonyl ene and Prins cyclisations
  作者：Claire A. M. Cariou、Benson M. Kariuki、John S. Snaith

  DOI：10.1039/b808644c

  日期：——

  An approach to 2,4,5-trisubstituted piperidines is reported, in which the key step is the Prins or carbonyl ene cyclisation of aldehydes of the type 1. Prins cyclisation catalysed by concentrated hydrochloric acid in CH2Cl2 at −78 °C afforded good yields of two of the four possible diastereomeric piperidines, with the 4,5-cis product 7 predominating in a diastereomeric ratio of up to 94 : 6. The diastereoselectivity of the cyclisation decreased as the 2-substituent increased in size, becoming unselective for very bulky 2-substituents. In contrast, cyclisation catalysed by MeAlCl2 in CH2Cl2 or CHCl3 at temperatures of between 20–60 °C, favoured the 4,5-trans diastereomer 8, in a diastereomeric ratio of up to 99 : 1. The low-temperature cyclisations catalysed by HCl proceed under kinetic control via a mechanism involving the development of significant carbocationic character, in which the 4,5-cis cation is more stable than the 4,5-trans cation as a result of overlap with the neighbouring oxygen. The cyclisations catalysed by MeAlCl2 proceed under thermodynamic control, affording the product in which both the 4- and 5-substituents are equatorial.

  报告了一种合成2,4,5-三取代哌啶的方法，其中关键步骤是醛类化合物1的Prins或羰基烯环化反应。在-78°C下，采用浓盐酸催化的CH2Cl2中进行的Prins环化反应，获得了四种可能的立体异构体中的两种良好产率，其中4,5-顺式产物7的产率在立体异构体比率上高达94:6。随着2-取代基体积的增大，环化反应的立体选择性降低，对于体积非常大的2-取代基体则变得无选择性。相比之下，在20–60°C的CH2Cl2或CHCl3中，MeAlCl2催化的环化反应则偏向于4,5-反式立体异构体8，其立体异构体比率高达99:1。由HCl催化的低温环化反应在动力学控制下进行，机制涉及显著的碳正离子特性，其中，4,5-顺式阳离子由于与相邻氧的重叠而比4,5-反式阳离子更稳定。而由MeAlCl2催化的环化反应则在热力学控制下进行，生成的产物中4-和5-取代基均为赤面配置。
• Synthesis of Natural Product-Inspired Inhibitors of <i>Mycobacterium tuberculosis</i> Mycothiol-Associated Enzymes: The First Inhibitors of GlcNAc-Ins Deacetylase
  作者：Belhu B. Metaferia、Brandon J. Fetterolf、Syed Shazad-ul-Hussan、Matthew Moravec、Jeremy A. Smith、Satyajit Ray、Maria-Teresa Gutierrez-Lugo、Carole A. Bewley

  DOI：10.1021/jm070669h

  日期：2007.12.13

  Synthesis and evaluation of a chemical library of inhibitors of the mycothiol biosynthesis enzyme GlcNAc-Ins deacetylase (MshB) and the mycothiol-dependent detoxification enzyme mycothiol-S-conjugate amidase (MCA) from Mycobacterium tuberculosis are reported. The library was biased to include structural features of a group of natural products previously shown to competitively inhibit MCA. Molecular docking studies that reproducibly placed the inhibitors in the active site of the enzyme MshB reveal the mode of binding and are consistent with observed biological activity.
• WO2019173327A5
  申请人：——

  公开号：WO2019173327A5

  公开（公告）日：2022-03-14
• Potent, Novel in Vitro Inhibitors of the <i>Pseudomonas </i><i>a</i><i>eruginosa</i> Deacetylase LpxC
  作者：Toni Kline、Niels H. Andersen、Eric A. Harwood、Jason Bowman、Andre Malanda、Stephanie Endsley、Alice L. Erwin、Michael Doyle、Susan Fong、Alex L. Harris、Brian Mendelsohn、Khisimuzi Mdluli、Christian R. H. Raetz、C. Kendall Stover、Pamela R. Witte、Asha Yabannavar、Shuguang Zhu

  DOI：10.1021/jm010579r

  日期：2002.7.1

  Deacetylation of uridyldiphospho-3-O-(R-hydroxydecanoyl)-N-acetylglucosamine by LpxC is the first committed step in the Pseudomonas aeruginosa biosynthetic pathway to lipid A; homologous enzymes are found widely among Gram-negative bacteria. As an essential enzyme for which no inhibitors have yet been reported, the P. aeruginosa LpxC represents a highly attractive target for a novel antibacterial drug. We synthesized several focused small-molecule libraries, each composed of a variable aromatic ring, one of four heterocyclic/spacer moieties, and a hydroxamic acid and evaluated the LpxC inhibition of these compounds against purified P. aeruginosa enzyme. To ensure that the in vitro assay would be as physiologically relevant as possible, we synthesized a tritiated form of the specific P. aeruginosa glycolipid substrate and measured directly the enzymatically released acetate. Several of our novel compounds, predominantly those having fluorinated substituents on the aromatic ring and an oxazoline as the heterocyclic moiety, demonstrated in vitro IC50 values less than 1 muM. We now report the synthesis and in vitro evaluation of these P. aeruginosa LpxC inhibitors.