(3S,5R,6S)-2-oxo-3-isopropyl-5-((trimethylsilyl)ethynyl)-1-aza-4-oxabicyclo<4.3.0>nonane | 132127-44-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 恶嗪烷类
• 英文名称: (3S,5R,6S)-2-oxo-3-isopropyl-5-((trimethylsilyl)ethynyl)-1-aza-4-oxabicyclo<4.3.0>nonane
• 英文别名: (3S,5R,6S)-2-oxo-3-isopropyl-5-[(trimethylsilyl)ethynyl]-1-aza-4-oxabicyclo[4.3.0]nonane；(1R,3S,8aS)-3-propan-2-yl-1-(2-trimethylsilylethynyl)-6,7,8,8a-tetrahydro-1H-pyrrolo[2,1-c][1,4]oxazin-4-one
• CAS: 132127-44-7
• 化学式: C₁₅H₂₅NO₂Si
• 分子量: 279.454
• InChiKey: GYCFFYWWDVXSPO-MJBXVCDLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.28
• 重原子数：
  19.0
• 可旋转键数：
  1.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  29.54
• 氢给体数：
  0.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (3S,5R,6S)-2-oxo-3-isopropyl-5-((trimethylsilyl)ethynyl)-1-aza-4-oxabicyclo<4.3.0>nonane 在 盐酸 、 硫酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 38.0h， 生成 tert-butyl (2S,4'R,2'S)-2-isopropyl-4-(pyrrolidin-2'yl)-3-oxohex-5-ynoate
  参考文献：
  名称：

  Synthesis of proline-valine pseudodipeptide enol lactones, serine protease inhibitors

  摘要：

  Pseudodipeptides of proline-valine that incorporate protio or halo enol lactone moieties have been synthesized from common acetylenic acid precursors; in each case, two diasteromers were prepared in enantiomerically pure form. The preparation began with isomeric propargylic alcohols derived from L-prolinal, which are further elaborated into the methyleneoxy valine pseudodipeptide analogues via an oxalactam intermediate. Stereochemical assignments were made by comparisons of nuclear Overhauser enhancement factors. The pseudodipeptide acetylenic acids could by cyclized to the protio enol lactones by mercuric salts and could be elaborated to tetrapeptide analogues either before or after cyclization. The relative stability of the two diastereomeric enol lactone systems toward intramolecular acyl transfer could be rationalized by molecular mechanics energy calculations on ground-state and tetrahedral intermediates believed to be involved in the reaction. While the halo enol lactones derived from the pseudotetrapeptides proved to be very unstable, they could be prepared from the n-butyl carbamate derivatives of the dipeptide. An evaluation of these protio and halo enol lactone systems as inhibitors of serine proteases will be discussed elsewhere.

  DOI：

  10.1021/jo00008a011
• 作为产物：
  描述：

  (S)-N-Boc-吡咯烷-2-甲醛 N-(叔丁氧羰基)-L-脯氨醛 在 乙基溴化镁 、 potassium hydride 、 对甲苯磺酸 、 N,N'-羰基二咪唑 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 反应 9.75h， 生成 (3S,5R,6S)-2-oxo-3-isopropyl-5-((trimethylsilyl)ethynyl)-1-aza-4-oxabicyclo<4.3.0>nonane
  参考文献：
  名称：

  Synthesis of proline-valine pseudodipeptide enol lactones, serine protease inhibitors

  摘要：

  Pseudodipeptides of proline-valine that incorporate protio or halo enol lactone moieties have been synthesized from common acetylenic acid precursors; in each case, two diasteromers were prepared in enantiomerically pure form. The preparation began with isomeric propargylic alcohols derived from L-prolinal, which are further elaborated into the methyleneoxy valine pseudodipeptide analogues via an oxalactam intermediate. Stereochemical assignments were made by comparisons of nuclear Overhauser enhancement factors. The pseudodipeptide acetylenic acids could by cyclized to the protio enol lactones by mercuric salts and could be elaborated to tetrapeptide analogues either before or after cyclization. The relative stability of the two diastereomeric enol lactone systems toward intramolecular acyl transfer could be rationalized by molecular mechanics energy calculations on ground-state and tetrahedral intermediates believed to be involved in the reaction. While the halo enol lactones derived from the pseudotetrapeptides proved to be very unstable, they could be prepared from the n-butyl carbamate derivatives of the dipeptide. An evaluation of these protio and halo enol lactone systems as inhibitors of serine proteases will be discussed elsewhere.

  DOI：

  10.1021/jo00008a011

文献信息

• REED, PETER E.;KATZENELLENBOGEN, JOHN A., J. ORG. CHEM., 56,(1991) N, C. 2624-2634
  作者：REED, PETER E.、KATZENELLENBOGEN, JOHN A.

  DOI：——

  日期：——
• Synthesis of proline-valine pseudodipeptide enol lactones, serine protease inhibitors
  作者：Peter E. Reed、John A. Katzenellenbogen

  DOI：10.1021/jo00008a011

  日期：1991.4

  Pseudodipeptides of proline-valine that incorporate protio or halo enol lactone moieties have been synthesized from common acetylenic acid precursors; in each case, two diasteromers were prepared in enantiomerically pure form. The preparation began with isomeric propargylic alcohols derived from L-prolinal, which are further elaborated into the methyleneoxy valine pseudodipeptide analogues via an oxalactam intermediate. Stereochemical assignments were made by comparisons of nuclear Overhauser enhancement factors. The pseudodipeptide acetylenic acids could by cyclized to the protio enol lactones by mercuric salts and could be elaborated to tetrapeptide analogues either before or after cyclization. The relative stability of the two diastereomeric enol lactone systems toward intramolecular acyl transfer could be rationalized by molecular mechanics energy calculations on ground-state and tetrahedral intermediates believed to be involved in the reaction. While the halo enol lactones derived from the pseudotetrapeptides proved to be very unstable, they could be prepared from the n-butyl carbamate derivatives of the dipeptide. An evaluation of these protio and halo enol lactone systems as inhibitors of serine proteases will be discussed elsewhere.