(2R,5S)-2-tert-butyl-5-methyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one | 86046-11-9

• 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: (2R,5S)-2-tert-butyl-5-methyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one
• 英文别名: 1H,3H-Pyrrolo[1,2-c]oxazol-1-one, 3-(1,1-dimethylethyl)tetrahydro-7a-methyl-, (3R,7aS)-；(3R,7aS)-3-tert-butyl-7a-methyl-3,5,6,7-tetrahydropyrrolo[1,2-c][1,3]oxazol-1-one
• CAS: 86046-11-9
• 化学式: C₁₁H₁₉NO₂
• 分子量: 197.277
• InChiKey: VQVJNVDGTWMQEX-KCJUWKMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  14
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.91
• 拓扑面积：
  29.5
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  (2R,5S)-2-tert-butyl-5-methyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one 在 盐酸 作用下， 反应 16.0h， 以92%的产率得到(S)-2-甲基脯氨酸
  参考文献：
  名称：

  Synthesis, conformational properties, and antibody recognition of peptides containing .beta.-turn mimetics based on .alpha.-alkylproline derivatives

  摘要：

  Peptide recognition by monoclonal antibodies may provide a useful model for drug development, in particular to test the effects of conformational restriction on ligand binding. We have tested the influence of novel peptide mimetics upon conformation and binding affinity for the case of monoclonal antibodies raised to a peptide antigen which displays a preference for a beta-turn conformation in aqueous solution. Two monoclonals were isolated that recognized the peptide Ac-Tyr-Pro-Tyr-Asp-Val-Pro-Asp-Tyr-Ala specifically at the beta-turn formed by Tyr-Pro-Tyr-Asp. Peptide analogues were then synthesized containing mimetics designed to stabilize this conformation. One, analogue (3), contained a spirocyclic gamma-lactam bridge between the alpha-position of proline-2 and the N atom of tyrosine-3, while another (2) contained (S)-alpha-methylproline at position 2. NMR spectroscopy and molecular modeling suggest that both analogues adopt reverse-turn conformations stabilized relative to that in the native sequence. For the (S)-alpha-methylproline analogue binding to both monoclonal antibodies was substantially improved, compared with the native antigen, whereas the gamma-lactam analogue (3) was not recognized by either antibody. Quantitative equilibrium ultrafiltration binding assays showed that the affinities of the (S)-alpha-methylproline analogue (2) for the two antibodies were improved over those measured with the native antigen by -2.3 and -0.65 kcal/mol. The origins of these free energy differences cannot be explained wholly on the basis of presumed extra hydrophobic contacts between the new methyl substituent and the antigen binding sites. We propose that the increased conformational stability of the analogue plays a decisive role, implying that the reverse turn detected in the native antigen, possibly a type-I turn, is important for recognition by the two antibodies.

  DOI：

  10.1021/jm00110a005
• 作为产物：
  描述：

  Lithium; (R)-3-tert-butyl-6,7-dihydro-5H-pyrrolo[1,2-c]oxazol-1-olate 、 碘甲烷 以 四氢呋喃 、 正己烷 为溶剂， 以93%的产率得到(2R,5S)-2-tert-butyl-5-methyl-1-aza-3-oxabicyclo<3.3.0>octan-4-one
  参考文献：
  名称：

  不损失光学活性的氨基酸烷基化：α-取代的脯氨酸衍生物的制备。手性自我复制案例

  摘要：

  制备 d'un enolate par 缩合脱脯氨酸 avec le 新戊醛 suvie de 质子化。Etude des反应 de cet enolate avec divers 亲电试剂。新戊醛缩合氨基酸

  DOI：

  10.1021/ja00354a034

文献信息

• Diamine Ligands for Asymmetric Catalysis: Facile Synthesis of C2-Symmetric Piperazines from Seebach’s Oxazolidinone
  作者：Zbigniew Kałuża、Rafał Ćwiek、Mirosław Dygas、Przemysław Kalicki

  DOI：10.1055/s-0034-1378341

  日期：——

  C 2 -Symmetrical hemiaminal ethers and diamines with a piperazine core were synthesized starting from Seebach’s oxazolidinone. The new methodology is based on the dimerization of α-amino aldehydes to bicyclic bishemiaminal ethers, followed by reduction to the corresponding diamines. Several enantiopure piperazine derivatives bearing either methyl or bulky groups including isopropyl and aryl at the

  从Seebach's 恶唑烷酮开始合成具有哌嗪核心的C 2 -对称半胺醛醚和二胺。新方法基于将 α-氨基醛二聚化为双环双半胺醛醚，然后还原为相应的二胺。应用该方法获得了几种在桥头碳原子处带有甲基或大体积基团（包括异丙基和芳基）的对映纯哌嗪衍生物。在铜催化的内消旋 -1,2-二醇的不对称酰化中对新配体的初步筛选产生了有希望的结果（高达 92% ee）。
• Peptides
  申请人：THE UPJOHN COMPANY

  公开号：EP0173481A2

  公开（公告）日：1986-03-05

  Novel peptides which can act to inhibit renin and can have utility in the diagnosis and control of renin-dependent hypertension, and intermediates in the preparation of both the new and known renin-inhibiting peptides.

  可抑制肾素并可用于诊断和控制肾素依赖性高血压的新型肽，以及制备新型和已知肾素抑制肽的中间体。
• Renin-inhibiting peptides
  申请人：THE UPJOHN COMPANY

  公开号：EP0486478A2

  公开（公告）日：1992-05-20

  A renin inhibitory peptide comprising a N-alkylhistidine moiety at the position corresponding to the 9-position of the human renin substrate.

  一种肾素抑制肽，在与人类肾素底物 9 位相对应的位置上包含一个 N-烷基组氨酸分子。
• An improved method of oxazolidinone hydrolysis in the asymmetric synthesis of α-alkylprolines
  作者：Michael J. Genin、Paul W. Baures、Rodney L. Johnson

  DOI：10.1016/s0040-4039(00)73294-1

  日期：1994.7

  An improvement in Seebach's method for the synthesis of alpha-alkylprolines is reported wherein the hydrolysis of the chiral oxazolidinone 2 is performed on a suspension of silica gel in MeOH/H2O. Following hydrolysis, the pure alpha-alkylproline can he obtained by filtration thereby avoiding a tedious ion exchange purification.
• US4880781A
  申请人：——

  公开号：US4880781A

  公开（公告）日：1989-11-14