{(1S)-1-[(4R)-4-(3-hydroxy-propyl)-5-oxo-tetrahydro-furan-(2S)-2-yl]-2-phenyl-ethyl} carbamic acid tert-butyl ester | 333405-32-6

• 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: {(1S)-1-[(4R)-4-(3-hydroxy-propyl)-5-oxo-tetrahydro-furan-(2S)-2-yl]-2-phenyl-ethyl} carbamic acid tert-butyl ester
• 英文别名: tert-butyl N-[(1S)-1-[(2S,4R)-4-(3-hydroxypropyl)-5-oxooxolan-2-yl]-2-phenylethyl]carbamate
• CAS: 333405-32-6
• 化学式: C₂₀H₂₉NO₅
• 分子量: 363.454
• InChiKey: BLOZZDRBZSMLAU-IKGGRYGDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  {(1S)-1-[(4R)-4-(3-hydroxy-propyl)-5-oxo-tetrahydro-furan-(2S)-2-yl]-2-phenyl-ethyl} carbamic acid tert-butyl ester 在 N-甲基吗啉 、 咪唑 、 盐酸 、 sodium hydroxide 、 乙二胺四乙酸 、 1-羟基苯并三唑 作用下， 以 1,4-二氧六环 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 反应 52.83h， 生成 (S)-N-((1S,2S,4R)-1-Benzyl-2,7-dihydroxy-4-isobutylcarbamoyl-heptyl)-2-tert-butoxycarbonylamino-succinamic acid benzyl ester
  参考文献：
  名称：

  Rational design and synthesis of selective BACE-1 inhibitors

  摘要：

  An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2003.11.061
• 作为产物：
  描述：

  tert-butyl (1S)-1-[(2S)-5-oxotetrahydrofuran-2-yl]-2-phenylethylcarbamate 在 Wilkinson's catalyst 、 lithium diisopropyl amide 、 儿萘酚硼烷 作用下， 以 四氢呋喃 为溶剂， 反应 2.92h， 生成 {(1S)-1-[(4R)-4-(3-hydroxy-propyl)-5-oxo-tetrahydro-furan-(2S)-2-yl]-2-phenyl-ethyl} carbamic acid tert-butyl ester
  参考文献：
  名称：

  合成包含Phe-Arg羟乙烯二肽等排物的三肽衍生物。

  摘要：

  合成了被保护的Phe-Arg的羟乙烯二肽等排体和三肽衍生物1作为潜在的肽酶抑制剂的成分。这些合成成功的关键是在容易还原的内酯存在下的选择性铑催化的硼氢化反应。在施陶丁格反应的基础上，将叠氮化物方便地一锅转化为双保护的胍。

  DOI：

  10.1021/ol015612i

文献信息

• Synthesis of a Tripeptide Derivative Containing the Phe-Arg Hydroxyethylene Dipeptide Isostere
  作者：Matthias Brewer、Daniel H. Rich

  DOI：10.1021/ol015612i

  日期：2001.3.1

  The protected hydroxyethylene dipeptide isostere of Phe-Arg and the tripeptide derivative 1 were synthesized as components of potential peptidase inhibitors. Key to the success of these syntheses is selective rhodium-catalyzed hydroboration in the presence of a readily reduced lactone. A convenient one-pot conversion of azides to diprotected guanidines was developed on the basis of the Staudinger reaction

  合成了被保护的Phe-Arg的羟乙烯二肽等排体和三肽衍生物1作为潜在的肽酶抑制剂的成分。这些合成成功的关键是在容易还原的内酯存在下的选择性铑催化的硼氢化反应。在施陶丁格反应的基础上，将叠氮化物方便地一锅转化为双保护的胍。
• Rational design and synthesis of selective BACE-1 inhibitors
  作者：Stephen F. Brady、Satendra Singh、Ming-Chih Crouthamel、M.Katharine Holloway、Craig A. Coburn、Victor M. Garsky、Michael Bogusky、Michael W. Pennington、Joseph P. Vacca、Daria Hazuda、Ming-Tain Lai

  DOI：10.1016/j.bmcl.2003.11.061

  日期：2004.2

  An effective approach for enhancing the selectivity of beta-site amyloid precursor protein cleaving enzyme (BACE 1) inhibitors is developed based on the unique features of the S1' pocket of the enzyme. A series of low molecular weight ( < 600) compounds were synthesized with different moieties at the P1' position. The selectivity of BACE 1 inhibitors versus cathepsin D and renin was enhanced 120-fold by replacing the hydrophobic propyl group with a hydrophilic propionic acid group. (C) 2003 Elsevier Ltd. All rights reserved.