3-hydroxy-2,2-dimethyl-N-[1-methyl-1-(N,N-dimethylcarbamoyl)-2-phenylethyl]propanamide | 266338-67-4

• 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: 3-hydroxy-2,2-dimethyl-N-[1-methyl-1-(N,N-dimethylcarbamoyl)-2-phenylethyl]propanamide
• 英文别名: 2-benzyl-2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)amino]-N,N-dimethylpropanamide；N-[1-(dimethylamino)-2-methyl-1-oxo-3-phenylpropan-2-yl]-3-hydroxy-2,2-dimethylpropanamide
• CAS: 266338-67-4
• 化学式: C₁₇H₂₆N₂O₃
• 分子量: 306.405
• InChiKey: MFHKVDSDECRDEO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  22
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  3-hydroxy-2,2-dimethyl-N-[1-methyl-1-(N,N-dimethylcarbamoyl)-2-phenylethyl]propanamide 在 盐酸 作用下， 以 四氢呋喃 为溶剂， 反应 26.0h， 以95%的产率得到2-benzyl-2-[(3-hydroxy-2,2-dimethyl-1-oxopropyl)amino]propanoic acid
  参考文献：
  名称：

  Synthesis of 16-Membered Cyclic Depsipeptidesvia Direct Amide Cyclization

  摘要：

  The 2,2-disubstituted 2H-azirin-3-amines 5 (3-amino-2H-azirines) were used as synthons for alpha,alpha-disubstituted a-amino acids in the preparation of 16-membered cyclic depsipeptides 13. The linear precursors containing four alpha,alpha-disubstituted alpha-amino acids, the pentapeptides 12, were synthesized from beta-hydroxy acids 4 via the 'azirine/oxazolone method' (Scheme 2). The 16-membered cyclic depsipeptides 13 were prepared via 'direct amide cyclization' in good-to-excellent yields (Schemes 3 and 4). In addition to the desired cyclic monomer 13, which was obtained as the main product, the cyclodimer 14 could also be isolated. The cyclization conditions were investigated and found to be optimum with HCl in toluene at 100 degrees. The structure and conformation of the cyclic depsipeptide 13b was established by X-ray crystallography.

  DOI：

  10.1002/(sici)1522-2675(20000119)83:1<233::aid-hlca233>3.0.co;2-1
• 作为产物：
  描述：

  2,2-二甲基-3-羟基丙酸 、 2-benzyl-3-(dimethylamino)-2-methyl-2H-azirine 以 四氢呋喃 为溶剂， 反应 24.0h， 以88%的产率得到3-hydroxy-2,2-dimethyl-N-[1-methyl-1-(N,N-dimethylcarbamoyl)-2-phenylethyl]propanamide
  参考文献：
  名称：

  通过环二聚作用具有交替的β-羟基和α-氨基酸的14元环二肽

  摘要：

  描述了在“直接酰胺环化”（DAC）条件下1型β-羟基酰胺的环二聚（孪生）。尽管其他偶联方法也可得出中等结果，但通过DAC可获得最佳收率，环二聚体10可达88％。在所有情况下，当从外消旋物质开始时，仅分离出反式取代的环二肽。简单的分子模型表明，环二聚体的形成在热力学上比环聚单体的形成稍微更有利。由于分子内氢键的存在，优选形成环二聚体的提议不能通过X射线晶体学证实。还研究了取代基在氨基酸和羟基酸部分中的影响。结果表明，仅当羟基酸部分被α，α-二取代时，环二聚作用才成功。

  DOI：

  10.1016/j.tet.2005.11.002

文献信息

• 14-Membered cyclodepsipeptides with alternating β-hydroxy and α-amino acids by cyclodimerization
  作者：Boyan Iliev、Anthony Linden、Roland Kunz、Heinz Heimgartner

  DOI：10.1016/j.tet.2005.11.002

  日期：2006.2

  cyclodimer 10. In all cases, when starting with racemic material, only the trans-substituted cyclodepsipeptides were isolated. Simple molecular modeling revealed that the formation of the cyclodimer is thermodynamically slightly more favorable than that of the cyclomonomer. The proposal that cyclodimer formation is preferred because of the presence of intramolecular H-bonds could not be confirmed by X-ray

  描述了在“直接酰胺环化”（DAC）条件下1型β-羟基酰胺的环二聚（孪生）。尽管其他偶联方法也可得出中等结果，但通过DAC可获得最佳收率，环二聚体10可达88％。在所有情况下，当从外消旋物质开始时，仅分离出反式取代的环二肽。简单的分子模型表明，环二聚体的形成在热力学上比环聚单体的形成稍微更有利。由于分子内氢键的存在，优选形成环二聚体的提议不能通过X射线晶体学证实。还研究了取代基在氨基酸和羟基酸部分中的影响。结果表明，仅当羟基酸部分被α，α-二取代时，环二聚作用才成功。
• Synthesis of 16-Membered Cyclic Depsipeptidesvia Direct Amide Cyclization
  作者：Kristian N. Koch、Anthony Linden、Heinz Heimgartner

  DOI：10.1002/(sici)1522-2675(20000119)83:1<233::aid-hlca233>3.0.co;2-1

  日期：2000.1.19

  The 2,2-disubstituted 2H-azirin-3-amines 5 (3-amino-2H-azirines) were used as synthons for alpha,alpha-disubstituted a-amino acids in the preparation of 16-membered cyclic depsipeptides 13. The linear precursors containing four alpha,alpha-disubstituted alpha-amino acids, the pentapeptides 12, were synthesized from beta-hydroxy acids 4 via the 'azirine/oxazolone method' (Scheme 2). The 16-membered cyclic depsipeptides 13 were prepared via 'direct amide cyclization' in good-to-excellent yields (Schemes 3 and 4). In addition to the desired cyclic monomer 13, which was obtained as the main product, the cyclodimer 14 could also be isolated. The cyclization conditions were investigated and found to be optimum with HCl in toluene at 100 degrees. The structure and conformation of the cyclic depsipeptide 13b was established by X-ray crystallography.