(2S)-2-benzyloxy-3-ethoxy-2-methyl-3-oxo-propanoic acid | 2006-97-5

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: (2S)-2-benzyloxy-3-ethoxy-2-methyl-3-oxo-propanoic acid
• 英文别名: S-(-)-Benzyloxy-methylmalonsaeure-monoethylester-chlorid；(S)-2-(Benzyloxy)-3-ethoxy-2-methyl-3-oxopropanoic acid；(2S)-3-ethoxy-2-methyl-3-oxo-2-phenylmethoxypropanoic acid
• CAS: 2006-97-5
• 化学式: C₁₃H₁₆O₅
• 分子量: 252.267
• InChiKey: ZJAXMXGTROJZOK-ZDUSSCGKSA-N

物化性质

• 沸点：
  98-106 °C(Press: 0.002 Torr)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  18
• 可旋转键数：
  7
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S)-2-benzyloxy-3-ethoxy-2-methyl-3-oxo-propanoic acid 在 氯化亚砜 作用下， 生成 S-(+)-2-Benzoyloxy-2-methyl-butan-diol-(1.4)-bis-(4-nitro-benzoat)
  参考文献：
  名称：

  光学优化的甲基苄基氧基丙二酸酯和最佳免疫试剂。57.米特伊龙·尤伯·穆特尔恩·科纳洛德

  摘要：

  描述了（S）-和（R）-甲基苄氧基丙二酸的单乙酯氯化物的合成，它们是麦角胺合成的中间体。它们的绝对构型是通过将左旋对映体与S -（+）-柠檬酸连接而确定的。

  DOI：

  10.1002/hlca.19630460649
• 作为产物：
  描述：

  2-羟基-2-甲基丙二酸二乙酯 在 horse liver acetone 、 Tris buffer 、 sodium hydride 作用下， 以 正庚烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.0h， 生成 (2S)-2-benzyloxy-3-ethoxy-2-methyl-3-oxo-propanoic acid
  参考文献：
  名称：

  Asymmetric synthesis of (R)-(−)-chlozolinate through a chemoenzymatic procedure

  摘要：

  A new asymmetric synthesis of (R)-chlozolinate 1, an important antifungal agent, based on the enzymatic asymmetrization of diethyl 2-benzyloxy-2-methylmalonate, is reported. (C) 2001 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(01)00040-4

文献信息

• [EN] TARGETED NOTCH PATHWAY INHIBITORS<br/>[FR] INHIBITEURS DE LA VOIE DE NOTCH CIBLÉE
  申请人：HOFFMANN LA ROCHE

  公开号：WO2016198366A1

  公开（公告）日：2016-12-15

  The instant invention relates to novel conjugates of formula (I): S - L - A (I) or salts thereof, wherein A is a gamma-secretase inhibitor, L is a linker and S is a peptidase-specific substrate, as well as processes for their manufacture, pharmaceutical compositions comprising them, and their use as medicaments, especially for the treatment of renal diseases and tissue damage in the kidney.

  本发明涉及式(I)的新型共轭物：S - L - A (I)或其盐，其中A为γ-分泌酶抑制剂，L为连接子，S为肽酶特异性底物，以及它们的制备方法、包含它们的药物组合物及其作为药物，特别是用于治疗肾脏疾病和肾脏组织损伤的用途。
• Totalsynthese von nat�rlichem ?-Tocopherol. 4. Mitteilung. Aufbau des Chromanringsystems aus Trimethylhydrochinon und einem optisch aktiven C4- bzw. C5-Synthon
  作者：Richard Barner、Max Schmid

  DOI：10.1002/hlca.19790620735

  日期：1979.10.31

  Total Synthesis of Natural α-Tocopherol

  天然α-生育酚的全合成
• Targeted γ-Secretase Inhibition To Control the Notch Pathway in Renal Diseases
  作者：Lucienne Juillerat-Jeanneret、Alexander Flohr、Manfred Schneider、Isabelle Walter、Jean-Christophe Wyss、Rajesh Kumar、Dela Golshayan、Johannes D. Aebi

  DOI：10.1021/acs.jmedchem.5b00912

  日期：2015.10.22

  Notch is a membrane inserted protein activated by the membrane-inserted gamma-secretase proteolytic complex. The Notch pathway is a potential therapeutic target for the treatment of renal diseases but also controls the function of other cells, requiring cell-targeting of Notch antagonists. Toward selective targeting, we have developed the gamma-secretase inhibitor-based prodrugs 13a and 15a as substrates for gamma-glutamyltranspeptidase (gamma-CT) and/or gamma-glutamylcy-dotransferase (gamma-GCT) as well as aminopeptidase A (APA), which are overexpressed in renal diseases, and have evaluated them in experimental in vitro and in vivo models. In nondiseased mice, the cleavage product from Ac-gamma-Glu-gamma-secretase inhibitor prodrug 13a (gamma-GT-targeting and gamma-GCT-targeting) but not from Ac-alpha-Glu-gamma-secretase inhibitor prodrug 15a (APA-targeting) accumulated in kidneys when compared to blood and liver. Potential nephroprotective effects of the gamma-secretase inhibitor targeted prodrugs were investigated in vivo in a mouse model of acute kidney injury, demonstrating that the expression of Notch1 and cleaved Notchl could be selectively down-regulated upon treatment with the Ac-gamma-Glu-gamma-secretase-inhibitor 13a.
• TARGETED NOTCH PATHWAY INHIBITORS
  申请人：F. Hoffmann-La Roche AG

  公开号：EP3307721B1

  公开（公告）日：2020-06-17