ethyl 4-<<(1,1-dimethylethoxy)carbonyl>amino>-2,2-difluoro-3-hydroxy-5-methylhexanoate | 106771-28-2

• 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: ethyl 4-<<(1,1-dimethylethoxy)carbonyl>amino>-2,2-difluoro-3-hydroxy-5-methylhexanoate
• 英文别名: Ethyl 4-<(tert-butyloxycarbonyl)amino>-2,2-difluoro-3-hydroxy-5-methylhexanoate；ethyl 2,2-difluoro-3-hydroxy-5-methyl-4-[(2-methylpropan-2-yl)oxycarbonylamino]hexanoate
• CAS: 106771-28-2
• 化学式: C₁₄H₂₅F₂NO₅
• 分子量: 325.353
• InChiKey: QZIHUOMGJVSSLC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.09
• 重原子数：
  22.0
• 可旋转键数：
  6.0
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.86
• 拓扑面积：
  84.86
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ethyl 4-<<(1,1-dimethylethoxy)carbonyl>amino>-2,2-difluoro-3-hydroxy-5-methylhexanoate 在 N-甲基吗啉 、 盐酸 、 重铬酸吡啶 、 3 A molecular sieve 、 溶剂黄146 作用下， 以 乙醚 、 二氯甲烷 、 乙腈 为溶剂， 反应 45.0h， 生成 ethyl 2,2-difluoro-4-<amino>-5-methyl-3-oxohexanoate
  参考文献：
  名称：

  Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

  摘要：

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

  DOI：

  10.1021/jm00163a063
• 作为产物：
  描述：

  二氟溴乙酸乙酯 、 tert-butyl (3-methyl-1-oxobutan-2-yl)carbamate 在 锌 作用下， 以 四氢呋喃 为溶剂， 以36%的产率得到ethyl 4-<<(1,1-dimethylethoxy)carbonyl>amino>-2,2-difluoro-3-hydroxy-5-methylhexanoate
  参考文献：
  名称：

  Synthesis of peptidyl fluoromethyl ketones and peptidyl .alpha.-keto esters as inhibitors of porcine pancreatic elastase, human neutrophil elastase, and rat and human neutrophil cathepsin G

  摘要：

  Comparison of MeO-Suc-Val-Pro-Phe-CO2Me (29) and MeO-Suc-Ala-Ala-Pro-Phe- CO2Me (25) with their corresponding trifluoromethyl ketones 9a and 9b, respectively, in rat and human neutrophil cathepsin G assays showed the alpha-keto esters to be more potent inhibitors. Likewise, Ac-Pro-Ala-Pro-Ala-CO2Me (21) was more potent than its corresponding trifluoromethyl ketone (9c) in both porcine pancreatic elastase and human neutrophil elastase assays. Within a set of Ala-Ala-Pro-Val-CF3 elastase inhibitors, the carbobenzyloxy (Cbz) N-protecting group conferred greater potency as a P5 site recognition unit for elastase than did dansyl, methoxysuccinyl, or tert-butyloxycarbonyl. Initial inhibition of elastase was greater when trifluoromethyl ketone 9f was added from a stock solution of dimethyl sulfoxide than when it had been buffer-equilibrated prior to assay, which suggests that the nonhydrated ketone is the more effective form of the inhibitor. The most potent elastase inhibitor we report is Na-(Ad-SO2)-N epsilon-(MeO-Suc)Lys-Pro-Val-CF3 (16) which has a Ki of 0.58 nM.

  DOI：

  10.1021/jm00163a063

文献信息

• Preparation of .alpha.,.alpha.-difluoro-.beta.-hydroxy esters via a modified Reformatsky reaction
  作者：Timothy T. Curran

  DOI：10.1021/jo00075a033

  日期：1993.11

  A modified Reformatsky reaction has been developed which allows for the reproducible preparation of alpha,alpha-difluoro-beta-hydroxy- and gamma-amino-alpha,alpha-difluoro-beta-hydroxy esters in good yield from the corresponding aldehyde, ketone, or alpha-N-carbamoyl aldehyde.
• PEET, NORTON P.;BURKHART, JOSEPH P.;ANGELASTRO, MICHAEL R.;GIROUX, EUGENE+, J. MED. CHEM., 33,(1990) N, C. 394-407
  作者：PEET, NORTON P.、BURKHART, JOSEPH P.、ANGELASTRO, MICHAEL R.、GIROUX, EUGENE+

  DOI：——

  日期：——