(S)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<3,3-difluoro-2,4-dioxo-1-<2-oxo-2-(phenylmethoxy)ethyl>-4-(1-pyrrolidinyl)butyl>-L-alaninimide | 145452-66-0

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: (S)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<3,3-difluoro-2,4-dioxo-1-<2-oxo-2-(phenylmethoxy)ethyl>-4-(1-pyrrolidinyl)butyl>-L-alaninimide
• 英文别名: benzyl (3S)-5,5-difluoro-3-[[(2S)-2-[[(2S)-3-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]butanoyl]amino]propanoyl]amino]-4,6-dioxo-6-pyrrolidin-1-ylhexanoate
• CAS: 145452-66-0
• 化学式: C₃₀H₄₂F₂N₄O₈
• 分子量: 624.682
• InChiKey: ZHLJGESDTVHNEZ-RRPUWOKSSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  44
• 可旋转键数：
  16
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  160
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  (S)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<3,3-difluoro-2,4-dioxo-1-<2-oxo-2-(phenylmethoxy)ethyl>-4-(1-pyrrolidinyl)butyl>-L-alaninimide 在 palladium on activated charcoal 氢气 作用下， 以 乙醇 为溶剂， 反应 5.0h， 以65%的产率得到(S)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<1-(carboxymethyl)-3,3-difluoro-2,4-dioxo-4-(1-pyrrolidinyl)butyl>-L-alaninimide
  参考文献：
  名称：

  Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme

  摘要：

  The synthesis of the peptidyl difluoro ketone 1, an inhibitor of interleukin-1beta converting enzyme (ICE), was accomplished by a route beginning with the reaction of BrZnCF2CO2Et (2) with (2S)-1-(tert-butyldimethyl-silyl)-4-oxo-2-azetidinecarboxaldehyde (3) to give a mixture of epimeric alcohols 4 and 5. Conversion of alcohol 5 to 1 was carried out by a sequence including the novel coupling of beta-lactam 17 and BOC-Ala-O(succinimide) to form lactone 18. An early attempt to synthesize 1 utilized the beta-lactam ketone 10 obtained in two steps from either 4 or 5. This underwent addition of ethanol and stereoselective migration of the tert-butyldimethylsilyl group to afford the mixed silyl ethyl ketal 12. Unfortunately, efforts to open the beta-lactam ring of 12 and couple the intermediate beta-amino ester 14 to BOC-Ala-O(succinimide) were complicated by an unexpected cyclization reaction. The difluoro ketone 1 was found to exist as a mixture of diastereomeric gamma-hydroxy lactone tautomers in chloroform solution.

  DOI：

  10.1021/jo00052a054
• 作为产物：
  描述：

  ethyl -α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate 在 lithium hydroxide 、 戴斯-马丁氧化剂 、 三乙胺 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 四氢呋喃 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 38.0h， 生成 (S)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<3,3-difluoro-2,4-dioxo-1-<2-oxo-2-(phenylmethoxy)ethyl>-4-(1-pyrrolidinyl)butyl>-L-alaninimide
  参考文献：
  名称：

  Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme

  摘要：

  The synthesis of the peptidyl difluoro ketone 1, an inhibitor of interleukin-1beta converting enzyme (ICE), was accomplished by a route beginning with the reaction of BrZnCF2CO2Et (2) with (2S)-1-(tert-butyldimethyl-silyl)-4-oxo-2-azetidinecarboxaldehyde (3) to give a mixture of epimeric alcohols 4 and 5. Conversion of alcohol 5 to 1 was carried out by a sequence including the novel coupling of beta-lactam 17 and BOC-Ala-O(succinimide) to form lactone 18. An early attempt to synthesize 1 utilized the beta-lactam ketone 10 obtained in two steps from either 4 or 5. This underwent addition of ethanol and stereoselective migration of the tert-butyldimethylsilyl group to afford the mixed silyl ethyl ketal 12. Unfortunately, efforts to open the beta-lactam ring of 12 and couple the intermediate beta-amino ester 14 to BOC-Ala-O(succinimide) were complicated by an unexpected cyclization reaction. The difluoro ketone 1 was found to exist as a mixture of diastereomeric gamma-hydroxy lactone tautomers in chloroform solution.

  DOI：

  10.1021/jo00052a054