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 | 864764-50-1

• 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: 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
• CAS: 864764-50-1
• 化学式: C₃₂H₅₉N₅O₇S
• 分子量: 657.916
• InChiKey: VJZSTILXVWWCRI-OSZANLPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  45
• 可旋转键数：
  20
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  192
• 氢给体数：
  5
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  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 、 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， 以83%的产率得到(2S)-N-[(1S)-1-{[(1S,2S)-1-[(3S,4R)-4-{[(1S)-1-(butylcarbamoyl)-2-methylpropyl]carbamoyl}-1-ethyl-5-oxopyrrolidin-3-yl]-1-hydroxy-4-methylpentan-2-yl]carbamoyl}-3-(methylsulfanyl)propyl]-2-acetamido-4-methylpentanamide
  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：

  (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