(4S,4aS,7S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-3,4,4a,5,6,7-hexahydropyrrolo[1,2-c][1,3]oxazine-7-carboxylic acid | 1235568-61-2

• 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: (4S,4aS,7S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-3,4,4a,5,6,7-hexahydropyrrolo[1,2-c][1,3]oxazine-7-carboxylic acid
• CAS: 1235568-61-2
• 化学式: C₁₃H₂₀N₂O₆
• 分子量: 300.312
• InChiKey: HVDUXOWKCQHPBG-VGMNWLOBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.77
• 拓扑面积：
  105
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (4S,4aS,7S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-3,4,4a,5,6,7-hexahydropyrrolo[1,2-c][1,3]oxazine-7-carboxylic acid 在 盐酸 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 三乙胺 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 49.58h， 生成
  参考文献：
  名称：

  Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate

  摘要：

  Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3 beta. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3 beta mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.079
• 作为产物：
  描述：

  tert-butyl (2S,5S)-1-benzyl-5-(2-ethoxycarbonylmethyl)pyrrolidine-2-carboxylate 在 六甲基磷酰三胺 、 锂硼氢 、 20 % Pd(OH)2/C 、 2,4,6-三异丙基苯磺酰叠氮化物 、 氢气 、 双(三甲基硅烷基)氨基钾 、 三乙胺 、 三苯基膦 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 水 为溶剂， 反应 24.0h， 生成 (4S,4aS,7S)-4-[(2-methylpropan-2-yl)oxycarbonylamino]-1-oxo-3,4,4a,5,6,7-hexahydropyrrolo[1,2-c][1,3]oxazine-7-carboxylic acid
  参考文献：
  名称：

  Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate

  摘要：

  Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3 beta. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3 beta mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 mu M). (C) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.09.079

文献信息

• Synthesis and Conformational Analysis of Bicyclic Extended Dipeptide Surrogates
  作者：Sujeewa Ranatunga、Wathsala Liyanage、Juan R. Del Valle

  DOI：10.1021/jo1008433

  日期：2010.8.6

  Regio- and diastereoselective reactions of a homoproline enolate enable the synthesis of novel extended dipeptide surrogates. Bicyclic carbamate 9 and fused β-lactam scaffold 11 were prepared from l-pyroglutamic acid via substrate-controlled electrophilic azidation. Synthesis of orthogonally protected hexahydropyrrolizine, hexahydropyrrolizinone, and hexahydropyrroloazepinone dipeptide surrogates relied

  高脯氨酸烯醇化物的区域和非对映选择性反应能够合成新的扩展二肽替代物。双环氨基甲酸酯9和融合 β-内酰胺支架11由l-焦谷氨酸通过底物控制的亲电叠氮化反应制备。正交保护的六氢吡咯嗪、六氢吡咯嗪酮和六氢吡咯氮杂二肽替代物的合成依赖于脯氨酸衍生物5 的烯丙基化，然后是 Curtius 重排以引入 N 端氨基甲酸酯基团。通过 X 射线衍射和分子建模的组合，总共评估了六种氮杂双环烷烃衍生物的扩展二肽的构象模拟。假定骨架二面角和 N 端到 C 端二肽距离的分析表明化合物 (α' S )- 14b和21近似于在 β 折叠中发现的二肽的构象，而三肽模拟物28在固态下也高度延伸. 结构数据表明，环大小和相对立体化学对这些支架作为 β 链模拟物的能力具有深远的影响，并应为相关构象探针的设计提供信息。
• Synthesis of GSK3β mimetic inhibitors of Akt featuring a novel extended dipeptide surrogate
  作者：Sujeewa Ranatunga、Juan R. Del Valle

  DOI：10.1016/j.bmcl.2011.09.079

  日期：2011.12

  Akt is a cardinal nodal point in PI3K signaling pathway and confers resistance to apoptosis through inactivation of regulatory substrates such as GSK3 beta. Efforts to inhibit the kinase activity of Akt have largely focused on targeting the ATP-binding domain of Akt. Here, we present the design and synthesis of conformationally constrained GSK3 beta mimics featuring a novel extended dipeptide surrogate core. This effort resulted in the identification of a novel substrate mimetic Akt inhibitor (11) with low micromolar activity in vitro (Akt1 IC50 = 3.1 mu M). (C) 2011 Elsevier Ltd. All rights reserved.