methyl (3R)-3-hydroxy-4-(triisopropysilyloxy)butanoate | 867266-61-3

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羟基酸及其衍生物
• 英文名称: methyl (3R)-3-hydroxy-4-(triisopropysilyloxy)butanoate
• 英文别名: (R)-3-hydroxy-4-triisopropylsilanyloxybutyric acid methyl ester；Methyl (3R)-3-hydroxy-4-[[tris(1-methylethyl)silyl]oxy]butanoate；methyl (3R)-3-hydroxy-4-tri(propan-2-yl)silyloxybutanoate
• CAS: 867266-61-3
• 化学式: C₁₄H₃₀O₄Si
• 分子量: 290.475
• InChiKey: MUGZYPGPRSTYQO-CYBMUJFWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  19
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.93
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  methyl (3R)-3-hydroxy-4-(triisopropysilyloxy)butanoate 在 lithium aluminium tetrahydride 、 D(+)-10-樟脑磺酸 、 三氧化硫吡啶 、 二异丁基氢化铝 、 三乙胺 作用下， 以 乙醚 、 正己烷 、 二氯甲烷 、 二甲基亚砜 为溶剂， 反应 2.33h， 生成 (R)-3-(3,4-dimethoxybenzyloxy)-4-(triisopropylsilyloxy)butanal
  参考文献：
  名称：

  对青霉素a的对映选择性合成，第一部分：C1-C12和C13-C28亚基的合成。

  摘要：

  DOI：

  10.1002/anie.200603653
• 作为产物：
  描述：

  methyl 4-triisopropysilyloxy-3-oxobutanoate 在 (S)-BinapRuBr₂ 氢气 作用下， 以 甲醇 为溶剂， 40.0 ℃ 、1.0 MPa 条件下， 反应 16.0h， 以92%的产率得到methyl (3R)-3-hydroxy-4-(triisopropysilyloxy)butanoate
  参考文献：
  名称：

  Synthetic route towards (5R,2′S,5′S,6′S)-ribosyl-diazepanone, an analogue core of the liposidomycins

  摘要：

  The synthesis of (5R,2'S,5'S,6'S)-ribosyl-diazepanone, an analogue core of liposidomycins is described. The core ribosyl seven-membered heterocycle of nucleoside antibiotic liposidomycins was formed by reductive amination of an alpha-ribosylamino ester derived from D-ribose, and an amino aldehyde derived from methyl 4-triisopropylsilyloxy-3-oxobutanoate, followed by a peptidic coupling reaction. (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetasy.2007.07.023

文献信息

• 4-((<i>R</i>)-2-{[6-((<i>S</i>)-3-Methoxypyrrolidin-1-yl)-2-phenylpyrimidine-4-carbonyl]amino}-3-phosphonopropionyl)piperazine-1-carboxylic Acid Butyl Ester (ACT-246475) and Its Prodrug (ACT-281959), a Novel P2Y₁₂ Receptor Antagonist with a Wider Therapeutic Window in the Rat Than Clopidogrel
  作者：Eva Caroff、Francis Hubler、Emmanuel Meyer、Dorte Renneberg、Carmela Gnerre、Alexander Treiber、Markus Rey、Patrick Hess、Beat Steiner、Kurt Hilpert、Markus A. Riederer

  DOI：10.1021/acs.jmedchem.5b00933

  日期：2015.12.10

  Recent post hoc analyses of several clinical trials with P2Y(12) antagonists showed the need for new molecules being fully efficacious as antiplatelet agents and having a reduced propensity to cause major bleeding. We have previously reported the discovery of the 2-phenylpyrimidine-4-carboxamide analogs as P2Y(12) antagonists with nanomolar potency in the disease-relevant platelet aggregation assay in human plasma. Herein we present the optimization steps that led to the discovery of clinical candidate ACT-246475 (30d). The key step was the replacement of the carboxylic acid functionality by a phosphonic acid group which delivered the most potent molecules of the program. In addition, low in vivo clearance in rat and dog was achieved for the first time. Since the bioavailability of 30d was low in rat and dog, we developed the bis((isopropoxycarbonyl)oxy)methyl ester prodrug (ACT-281959, 45). Compound 30d showed efficacy in the rat ferric chloride thrombosis model when administered intravenously as parent or orally as its prodrug 45. Moreover, 30d displays a wider therapeutic window as compared to clopidogrel in the rat surgical blood loss model.
• Enantioselective Synthesis of Oasomycin A, Part I: Synthesis of the C1–C12 and C13–C28 Subunits
  作者：David A. Evans、Pavel Nagorny、Kenneth J. McRae、Dominic J. Reynolds、Louis-Sebastian Sonntag、Filisaty Vounatsos、Risheng Xu

  DOI：10.1002/anie.200603653

  日期：2007.1.15
• Synthetic route towards (5R,2′S,5′S,6′S)-ribosyl-diazepanone, an analogue core of the liposidomycins
  作者：Bruno Drouillat、Yann Bourdreux、Delphine Perdon、Christine Greck

  DOI：10.1016/j.tetasy.2007.07.023

  日期：2007.8

  The synthesis of (5R,2'S,5'S,6'S)-ribosyl-diazepanone, an analogue core of liposidomycins is described. The core ribosyl seven-membered heterocycle of nucleoside antibiotic liposidomycins was formed by reductive amination of an alpha-ribosylamino ester derived from D-ribose, and an amino aldehyde derived from methyl 4-triisopropylsilyloxy-3-oxobutanoate, followed by a peptidic coupling reaction. (c) 2007 Elsevier Ltd. All rights reserved.