(2R-cis)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<2-<1,1-difluoro-2-oxo-2-(1-pyrrolidinyl)ethyl>tetrahydro-5-oxo-3-furanyl>-L-alaninimide | 145452-64-8

• 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: (2R-cis)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<2-<1,1-difluoro-2-oxo-2-(1-pyrrolidinyl)ethyl>tetrahydro-5-oxo-3-furanyl>-L-alaninimide
• 英文别名: tert-butyl N-[(2S)-1-[[(2S)-1-[[(2R,3S)-2-(1,1-difluoro-2-oxo-2-pyrrolidin-1-ylethyl)-5-oxooxolan-3-yl]amino]-1-oxopropan-2-yl]amino]-3-methyl-1-oxobutan-2-yl]carbamate
• CAS: 145452-64-8
• 化学式: C₂₃H₃₆F₂N₄O₇
• 分子量: 518.558
• InChiKey: PWUNPSNQFVEVBK-NXNVCVFFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.8
• 重原子数：
  36
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  143
• 氢给体数：
  3
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  (2R-cis)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<2-<1,1-difluoro-2-oxo-2-(1-pyrrolidinyl)ethyl>tetrahydro-5-oxo-3-furanyl>-L-alaninimide 在 palladium on activated charcoal lithium hydroxide 、 氢气 、 戴斯-马丁氧化剂 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 23.0 ℃ 、303.98 kPa 条件下， 反应 17.0h， 生成 (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：

  <2R-<2α,3α(S*)>>-<2-<<2-<1,1-difluoro-2-oxo-2-(1-pyrrolidinyl)ethyl>tetrahydro-5-oxo-3-furanyl>amino>-1-methyl-2-oxoethyl>carbamic acid, 1,1-dimethylethyl ester 在 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 6.0h， 生成 (2R-cis)-N-<(1,1-dimethylethoxy)carbonyl>-L-valyl-N-<2-<1,1-difluoro-2-oxo-2-(1-pyrrolidinyl)ethyl>tetrahydro-5-oxo-3-furanyl>-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

文献信息

• Synthesis of a peptidyl difluoro ketone bearing the aspartic acid side chain: an inhibitor of interleukin-1.beta. converting enzyme
  作者：Ralph P. Robinson、Kathleen M. Donahue

  DOI：10.1021/jo00052a054

  日期：1992.12

  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.