(4S)-isobutyl-(5S)-(2-methoxycarbonyl-(1S)-nitro-methyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester | 864764-42-1

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: (4S)-isobutyl-(5S)-(2-methoxycarbonyl-(1S)-nitro-methyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4S,5S)-5-[(2S)-4-methoxy-1-nitro-4-oxobutan-2-yl]-2,2-dimethyl-4-(2-methylpropyl)-1,3-oxazolidine-3-carboxylate
• CAS: 864764-42-1
• 化学式: C₁₉H₃₄N₂O₇
• 分子量: 402.488
• InChiKey: UOIJNUFHUDFPRP-DZKIICNBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  28
• 可旋转键数：
  9
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.89
• 拓扑面积：
  111
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (4S)-isobutyl-(5S)-(2-methoxycarbonyl-(1S)-nitro-methyl-ethyl)-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 dihydrogen hexachloroplatinate 、 sodium hydroxide 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 镍 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， -78.0~65.0 ℃ 、413.68 kPa 条件下， 反应 8.67h， 生成 tert-butyl N-[(2S)-1-[[(1S,2S)-1-[(3S,4R)-4-[[(2S)-1-(butylamino)-3-methyl-1-oxobutan-2-yl]carbamoyl]-1-ethyl-5-oxopyrrolidin-3-yl]-1-hydroxy-4-methylpentan-2-yl]amino]-4-methylsulfanyl-1-oxobutan-2-yl]carbamate
  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：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 在 Lindlar's catalyst 喹啉 、 cerium(III) chloride 、 1,5,7-三氮杂双环[4.4.0]癸-5-烯 、 氢气 作用下， 以 四氢呋喃 、 丙酮 、 苯 为溶剂， -78.0~20.0 ℃ 、101.33 kPa 条件下， 反应 53.08h， 生成 (4S)-isobutyl-(5S)-(2-methoxycarbonyl-(1S)-nitro-methyl-ethyl)-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.