-1-<3-(4-oxo-2-azetidinyl)-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine | 145452-62-6

• 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-(4-oxo-2-azetidinyl)-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine
• 英文别名: (R-(R*,S*))-1-[3-(4-oxo-2-azetidinyl)-2,2-difluoro-3-hydroxy-1-oxopropyl]pyrrolidine；(4S)-4-[(1R)-2,2-difluoro-1-hydroxy-3-oxo-3-pyrrolidin-1-ylpropyl]azetidin-2-one
• CAS: 145452-62-6
• 化学式: C₁₀H₁₄F₂N₂O₃
• 分子量: 248.23
• InChiKey: BGOCFLCGLGQOFJ-POYBYMJQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  17
• 可旋转键数：
  3
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  -1-<3-(4-oxo-2-azetidinyl)-2,2-difluoro-3-hydroxy-1-oxopropyl>pyrrolidine 在 lithium hydroxide 、 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 为溶剂， 反应 27.0h， 生成 Lithium; (3S,4R)-3-[(S)-2-((S)-2-tert-butoxycarbonylamino-3-methyl-butyrylamino)-propionylamino]-5,5-difluoro-4-hydroxy-6-oxo-6-pyrrolidin-1-yl-hexanoate
  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 -1-<(1,1-dimethylethyl)dimethylsilyl>-α,α-difluoro-β-hydroxy-4-oxo-2-azetidinepropanoate 在 氢氟酸 作用下， 以 吡啶 、 二氯甲烷 、 乙腈 为溶剂， 反应 3.5h， 生成 -1-<3-(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

• PEPTIDYL 4-AMINO-2,2-DIFLUORO-3-OXO-1,6-HEXANEDIOIC ACID DERIVATIVES AS ANTIINFLAMMATORY AGENTS
  申请人：PFIZER INC.

  公开号：EP0654041B1

  公开（公告）日：1998-07-01
• 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.