(4S,5S)-5-[(2R,3R)-2-((S)-1-Butylcarbamoyl-2-methyl-propylcarbamoyl)-1-methyl-5-oxo-pyrrolidin-3-yl]-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester | 864239-15-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (4S,5S)-5-[(2R,3R)-2-((S)-1-Butylcarbamoyl-2-methyl-propylcarbamoyl)-1-methyl-5-oxo-pyrrolidin-3-yl]-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester
• 英文别名: tert-butyl (4S,5S)-5-[(2R,3R)-2-[[(2S)-1-(butylamino)-3-methyl-1-oxobutan-2-yl]carbamoyl]-1-methyl-5-oxopyrrolidin-3-yl]-2,2-dimethyl-4-(2-methylpropyl)-1,3-oxazolidine-3-carboxylate
• CAS: 864239-15-6
• 化学式: C₂₉H₅₂N₄O₆
• 分子量: 552.755
• InChiKey: NALNOJXUBOKXBG-BMRYZAIJSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  39
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  117
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,5S)-5-[(2R,3R)-2-((S)-1-Butylcarbamoyl-2-methyl-propylcarbamoyl)-1-methyl-5-oxo-pyrrolidin-3-yl]-4-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 生成 [(S)-1-((S)-1-{(S)-[(2R,3R)-2-((S)-1-Butylcarbamoyl-2-methyl-propylcarbamoyl)-1-methyl-5-oxo-pyrrolidin-3-yl]-hydroxy-methyl}-3-methyl-butylcarbamoyl)-3-methylsulfanyl-propyl]-carbamic acid tert-butyl ester
  参考文献：
  名称：

  基于结构的设计，合成和碳环和杂环拟肽的memapsin 2（BACE）抑制活性。

  摘要：

  基于BACE的Tang-Ghosh七肽抑制剂1（OM99-2）的X射线晶体结构的分子建模，导致设计和合成了一系列受约束的P（1）'类似物。1个环戊烷环结合在P（1）'Ala甲基和该链的相邻亚甲基碳原子上。在P（2）'-P（4）'位点的逐步截短导致有效的截短的类似物5，对组织蛋白酶D具有良好的选择性。使用相同的骨架替换概念，一系列环戊烷，环戊酮，四氢呋喃，吡咯烷和吡咯烷酮合成的类似物在P和P'位点有相当大的变化。环戊酮和2-吡咯烷酮类似物45和57显示出较低的nM BACE抑制作用。

  DOI：

  10.1021/jm050142+
• 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 、 sodium hydroxide 、 sodium amalgam 、 cerium(III) chloride 、 disodium hydrogenphosphate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 氢气 、 sodium hydride 、 臭氧 、 N,N-二异丙基乙胺 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 、 丙酮 、 甲苯 、 苯 为溶剂， -78.0~80.0 ℃ 、101.33 kPa 条件下， 反应 10.08h， 生成 (4S,5S)-5-[(2R,3R)-2-((S)-1-Butylcarbamoyl-2-methyl-propylcarbamoyl)-1-methyl-5-oxo-pyrrolidin-3-yl]-4-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.
• Structure-Based Design, Synthesis, and Memapsin 2 (BACE) Inhibitory Activity of Carbocyclic and Heterocyclic Peptidomimetics
  作者：Stephen Hanessian、Hongying Yun、Yihua Hou、Gaoqiang Yang、Malken Bayrakdarian、Eric Therrien、Nicolas Moitessier、Silvio Roggo、Siem Veenstra、Marina Tintelnot-Blomley、Jean-Michel Rondeau、Christian Ostermeier、André Strauss、Paul Ramage、Paolo Paganetti、Ulf Neumann、Claudia Betschart

  DOI：10.1021/jm050142+

  日期：2005.8.1

  BACE led to the design and synthesis of a series of constrained P(1)' analogues. A cyclopentane ring was incorporated in 1 spanning the P(1)' Ala methyl group and the adjacent methylene carbon atom of the chain. Progressive truncation at the P(2)'-P(4)' sites led to a potent truncated analogue 5 with good selectivity over Cathepsin D. Using the same backbone replacement concept, a series of cyclopentane

  基于BACE的Tang-Ghosh七肽抑制剂1（OM99-2）的X射线晶体结构的分子建模，导致设计和合成了一系列受约束的P（1）'类似物。1个环戊烷环结合在P（1）'Ala甲基和该链的相邻亚甲基碳原子上。在P（2）'-P（4）'位点的逐步截短导致有效的截短的类似物5，对组织蛋白酶D具有良好的选择性。使用相同的骨架替换概念，一系列环戊烷，环戊酮，四氢呋喃，吡咯烷和吡咯烷酮合成的类似物在P和P'位点有相当大的变化。环戊酮和2-吡咯烷酮类似物45和57显示出较低的nM BACE抑制作用。