-1-<3-<1-<(1,1-dimethylethyl)dimethylsilyl>-4-oxo-2-azetidinyl>-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine | 145452-52-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酰胺类
• 英文名称: -1-<3-<1-<(1,1-dimethylethyl)dimethylsilyl>-4-oxo-2-azetidinyl>-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine
• 英文别名: (4S)-1-[tert-butyl(dimethyl)silyl]-4-[(1R)-2,2-difluoro-1-hydroxy-3-oxo-3-pyrrolidin-1-ylpropyl]azetidin-2-one
• CAS: 145452-52-4
• 化学式: C₁₆H₂₈F₂N₂O₃Si
• 分子量: 362.492
• InChiKey: USKCOJGCDASYDV-WCQYABFASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.21
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  60.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  (2S)-1-[(1,1-dimethylethyl)dimethylsilyl]-4-oxo-2-azetidinecarboxaldehyde 在 锌 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 44.25h， 生成 -1-<3-<1-<(1,1-dimethylethyl)dimethylsilyl>-4-oxo-2-azetidinyl>-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine
  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.