(5R,8RS)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane-1-carboxylic acid tert-butyl ester | 731807-68-4

• 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: (5R,8RS)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane-1-carboxylic acid tert-butyl ester
• 英文别名: (5R)-1-(tert-butoxycarbonyl)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane；tert-butyl (5R)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane-1-carboxylate
• CAS: 731807-68-4
• 化学式: C₁₂H₁₉NO₅
• 分子量: 257.287
• InChiKey: SBMHPNKTIZTCQP-LESKNEHBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.83
• 拓扑面积：
  76.1
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (5R,8RS)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane-1-carboxylic acid tert-butyl ester 在 sodium hydroxide 、 乙醇 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 2.92h， 生成 (2R,5'R)-3-[4-(2,6-dichlorobenzyloxy)phenyl]-2-(1-tert-butoxycarbonyl-6-oxo-1,7-diazaspiro[4.4]nonane-7-yl)propanoic acid
  参考文献：
  名称：

  Evaluation of Lactam-Bridged Neurotensin Analogues Adjusting ψ(Pro¹⁰) Close to the Experimentally Derived Bioactive Conformation of NT(8−13)

  摘要：

  The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a beta-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies showed that the restriction of Psi(Pro(10)) to approximately 130degrees leads to a more than 1000-fold increase of binding affinity for 1 (K-i = 12 nM) when compared to the more flexible analogue [NMeTyr(11)]NT(8-13).

  DOI：

  10.1021/jm049644y
• 作为产物：
  描述：

  (R)-methyl 2-allylpyrrolidine-2-carboxylate 在 sodium hydroxide 、 臭氧 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 75.82h， 生成 (5R,8RS)-8-hydroxy-6-oxo-7-oxa-1-azaspiro[4.4]nonane-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Evaluation of Lactam-Bridged Neurotensin Analogues Adjusting ψ(Pro¹⁰) Close to the Experimentally Derived Bioactive Conformation of NT(8−13)

  摘要：

  The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a beta-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies showed that the restriction of Psi(Pro(10)) to approximately 130degrees leads to a more than 1000-fold increase of binding affinity for 1 (K-i = 12 nM) when compared to the more flexible analogue [NMeTyr(11)]NT(8-13).

  DOI：

  10.1021/jm049644y

文献信息

• Improved synthesis of a [4.4]-spirolactam β-turn mimetic as surrogate of the didemnin side chain dipeptide Pro-N-Me-d-Leu
  作者：Marta Gutiérrez-Rodrı́guez、M.Teresa Garcı́a-López、Rosario Herranz

  DOI：10.1016/j.tet.2004.04.052

  日期：2004.6

  An efficient synthesis of [4.4]-spirolactam restricted derivatives of the didemnin side chain dipeptide l-Pro-N-Me-d-Leu is described. This methodology involves: (a) peptide coupling of N-Boc-2-allylproline with d-Leu-OBn; (b) OsO4/NaIO4 mediated allyl oxidation and intramolecular cyclization to the corresponding cyclic hemiaminals; and (c) NaBH4 mediated reduction of an intermediate N-acyliminium

  描述了一种有效的合成双嘧达明侧链二肽1-Pro- N -Me-d-Leu的[4.4]-螺内酰胺限制的衍生物。该方法涉及：（a）N -Boc-2-烯丙基脯氨酸与d-Leu-OBn的肽偶联；（b）OsO 4 / NaIO 4介导的烯丙基氧化和分子内环化成相应的环状半胱氨酸；（c）NaBH 4介导的中间N-酰基酰亚胺离子的还原。该合成策略比先前报道的合成[4.4]-螺内酰胺β-turn模拟物的策略提供了明显更好的结果。