(5S)-(1-ethyl-5-oxo-pyrrolidin-(3R)-yl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester | 864764-38-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (5S)-(1-ethyl-5-oxo-pyrrolidin-(3R)-yl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4S,5S)-5-[(3R)-1-ethyl-5-oxopyrrolidin-3-yl]-2,2-dimethyl-4-(2-methylpropyl)-1,3-oxazolidine-3-carboxylate
• CAS: 864764-38-5
• 化学式: C₂₀H₃₆N₂O₄
• 分子量: 368.517
• InChiKey: MFZRQROLJDTMBA-VYDXJSESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.9
• 拓扑面积：
  59.1
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (5S)-(1-ethyl-5-oxo-pyrrolidin-(3R)-yl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 4-二甲氨基吡啶 、 barium dihydroxide 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 水 为溶剂， 反应 4.17h， 生成 (5S)-((4S)-butylcarbamoyl-1-ethyl-5-oxo-pyrrolidin-(3R)-yl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereoselective Synthesis of Constrained Azacyclic Hydroxyethylene Isosteres as Aspartic Protease Inhibitors: Dipolar Cycloaddition and Related Methodologies toward Branched Pyrrolidine and Pyrrolidinone Carboxylic Acids

  摘要：

  [GRAPHICS]The synthesis of three vicinally substituted azacyclic carboxylic acids in enantiopure form was achieved from a common (x-amino aldehyde originating from (L)-leucine. Pyrrolidines and pyrrolidinones were elaborated from a,beta-unsaturated gamma-hydroxy-delta-amino acids via azomethine ylide 1,3dipolar addition and conjugate addition/cyclization strategies, respectively. The azacyclic amino acids were incorporated in a pseudopeptide now encompassing a hydroxyethylene isostere. Low nanomolar inhibition of BACE1, an enzyme implicated in the cascade of events leading to plaque formation in Alzheimer's disease, was found with a pyrrolidinone analogue.

  DOI：

  10.1021/jo050740w
• 作为产物：
  描述：

  (5S)-(1-formyl-2-methoxycarbonyl-ethyl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 、 二乙胺 在 sodium sulfate 、 三乙酰氧基硼氢化钠 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 84.0h， 以82%的产率得到(5S)-(1-ethyl-5-oxo-pyrrolidin-(3R)-yl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Stereoselective Synthesis of Constrained Azacyclic Hydroxyethylene Isosteres as Aspartic Protease Inhibitors: Dipolar Cycloaddition and Related Methodologies toward Branched Pyrrolidine and Pyrrolidinone Carboxylic Acids

  摘要：

  [GRAPHICS]The synthesis of three vicinally substituted azacyclic carboxylic acids in enantiopure form was achieved from a common (x-amino aldehyde originating from (L)-leucine. Pyrrolidines and pyrrolidinones were elaborated from a,beta-unsaturated gamma-hydroxy-delta-amino acids via azomethine ylide 1,3dipolar addition and conjugate addition/cyclization strategies, respectively. The azacyclic amino acids were incorporated in a pseudopeptide now encompassing a hydroxyethylene isostere. Low nanomolar inhibition of BACE1, an enzyme implicated in the cascade of events leading to plaque formation in Alzheimer's disease, was found with a pyrrolidinone analogue.

  DOI：

  10.1021/jo050740w

文献信息

• Stereoselective Synthesis of Constrained Azacyclic Hydroxyethylene Isosteres as Aspartic Protease Inhibitors: Dipolar Cycloaddition and Related Methodologies toward Branched Pyrrolidine and Pyrrolidinone Carboxylic Acids
  作者：Stephen Hanessian、Hongying Yun、Yihua Hou、Marina Tintelnot-Blomley

  DOI：10.1021/jo050740w

  日期：2005.8.1

  [GRAPHICS]The synthesis of three vicinally substituted azacyclic carboxylic acids in enantiopure form was achieved from a common (x-amino aldehyde originating from (L)-leucine. Pyrrolidines and pyrrolidinones were elaborated from a,beta-unsaturated gamma-hydroxy-delta-amino acids via azomethine ylide 1,3dipolar addition and conjugate addition/cyclization strategies, respectively. The azacyclic amino acids were incorporated in a pseudopeptide now encompassing a hydroxyethylene isostere. Low nanomolar inhibition of BACE1, an enzyme implicated in the cascade of events leading to plaque formation in Alzheimer's disease, was found with a pyrrolidinone analogue.