[(S)-1-((S)-1-{(S)-[(2S,3S)-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 | 864764-51-2

• 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: [(S)-1-((S)-1-{(S)-[(2S,3S)-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
• CAS: 864764-51-2
• 化学式: C₃₁H₅₇N₅O₇S
• 分子量: 643.889
• InChiKey: VNGGFEGEBFIAIB-UWBSNJKQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.43
• 重原子数：
  44.0
• 可旋转键数：
  17.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  166.17
• 氢给体数：
  5.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  [(S)-1-((S)-1-{(S)-[(2S,3S)-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 、 N-乙酰-L-亮氨酸 在 碘代三甲硅烷 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 0.5h， 以75%的产率得到(2S,3S)-3-[(1S,2S)-2-[[(2S)-2-[[(2S)-2-acetamido-4-methylpentanoyl]amino]-4-methylsulfanylbutanoyl]amino]-1-hydroxy-4-methylpentyl]-N-[(2S)-1-(butylamino)-3-methyl-1-oxobutan-2-yl]-1-methyl-5-oxopyrrolidine-2-carboxamide
  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)-((Z)-2-bromo-2-methoxycarbonyl-vinyl)-(4S)-isobutyl-2,2-dimethyl-oxazolidine-3-carboxylic acid tert-butyl ester 在 sodium hydroxide 、 sodium amalgam 、 disodium hydrogenphosphate 、 benzotriazol-1-yloxyl-tris-(pyrrolidino)-phosphonium hexafluorophosphate 、 sodium hydride 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 2.0h， 生成 [(S)-1-((S)-1-{(S)-[(2S,3S)-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：

  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