N-(benzyloxycarbonyl)-1,12-dodecyldiamine | 66095-20-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-(benzyloxycarbonyl)-1,12-dodecyldiamine
• 英文别名: carboxybenzyl dodecyl diamine；Benzyl N-(12-aminododecyl)carbamate；benzyl N-(12-aminododecyl)carbamate
• CAS: 66095-20-3
• 化学式: C₂₀H₃₄N₂O₂
• 分子量: 334.502
• InChiKey: ACMMAQCKZDNEIQ-UHFFFAOYSA-N

物化性质

• 沸点：
  477.5±28.0 °C(Predicted)
• 密度：
  0.994±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  24
• 可旋转键数：
  15
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  64.4
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-(benzyloxycarbonyl)-1,12-dodecyldiamine 在 三乙基硅烷 、 palladium on activated charcoal 、 N,N-二异丙基乙胺 作用下， 生成
  参考文献：
  名称：

  [EN] UREIDOPYRIMIDONE SUPRAMOLECULAR COMPLEXES FOR COMPOUND DELIVERY INTO CELLS
  [FR] COMPLEXES SUPRAMOLÉCULAIRES D'URÉIDOPYRIMIDONE POUR L'ADMINISTRATION DE COMPOSÉS DANS DES CELLULES

  摘要：

  本发明涉及一种颗粒，其包含一个超分子复合物，该复合物包括一个单功能和/或双功能亚基，包括四重氢键单元、无极性连接剂、尿素基团和聚乙二醇连接剂。单功能亚基包括一个功能基团。这些颗粒非常适合作为药物传递系统，因为它们可以结合并进入细胞，并具有缓慢释放的特性。

  公开号：

  WO2016028149A1
• 作为产物：
  描述：

  1,12-二氨基十二烷 、 碳酸苄基苯酯 以 乙醇 为溶剂， 以45%的产率得到N-(benzyloxycarbonyl)-1,12-dodecyldiamine
  参考文献：
  名称：

  Solid-Phase-Based Synthesis of Ureidopyrimidinone–Peptide Conjugates­ for Supramolecular Biomaterials

  摘要：

  Supramolecular polymers have shown to be powerful scaffolds for tissue engineering applications. Supramolecular biomaterials functionalized with ureidopyrimidinone (UPy) moieties, which dimerize via quadruple hydrogen-bond formation, are eminently suitable for this purpose. The conjugation of the UPy moiety to biologically active peptides ensures adequate integration into the supramolecular UPy polymer matrix. The structural complexity of UPy-peptide conjugates makes their synthesis challenging and until recently low yielding, thus restricted the access to structurally diverse derivatives. Here we report optimization studies of a convergent solid-phase based synthesis of UPy-modified peptides. The peptide moiety is synthesized using standard Fmoc solid-phase synthesis and the UPy fragment is introduced on the solid-phase simplifying the synthesis and purification of the final UPy-peptide conjugate. The convergent nature of the synthesis reduces the number of synthetic steps in the longest linear sequence compared to other synthetic approaches. We demonstrate the utility of the optimized route by synthesizing a diverse range of biologically active UPy-peptide bioconjugates in multimilligram scale for diverse biomaterial applications. 1 Introduction 2 Divergent Synthesis 3 Convergent Synthesis 4 UPy-Amine Strategy 5 UPy-Carboxylic Acid Strategy 6 Conclusion

  DOI：

  10.1055/s-0035-1560520

文献信息

• Noncovalent CDK12/13 dual inhibitors-based PROTACs degrade CDK12-Cyclin K complex and induce synthetic lethality with PARP inhibitor
  作者：Tian Niu、Kailin Li、Li Jiang、Zhesheng Zhou、Ju Hong、Xuankun Chen、Xiaowu Dong、Qiaojun He、Ji Cao、Bo Yang、Cheng-Liang Zhu

  DOI：10.1016/j.ejmech.2021.114012

  日期：2022.1

  challenge. By taking advantage of the emerging PROteolysis-TArgeting Chimeras (PROTACs) approach, we have synthesized a potent PROTAC degrader PP-C8 based on the noncovalent dual inhibitors of CDK12/13 and demonstrated its specificity for CDK12 over CDK13. Notably, PP-C8 induces profound degradation of cyclin K simultaneously and downregulates the mRNA level of DNA-damage response genes. Global proteomics

  细胞周期蛋白依赖性激酶 12 (CDK12) 在 DNA 损伤反应基因转录中起着至关重要的作用，最近已被证实是癌症治疗中的一个有希望的靶点。然而，现有的 CDK12 抑制剂会有效抑制其最接近的同种型 CDK13，这可能会导致潜在的毒性。因此，开发对 CDK13 具有同种型选择性的 CDK12 抑制剂仍然是一个挑战。通过利用新兴的 PROteolysis-TArgeting Chimeras (PROTACs) 方法，我们合成了一种基于 CDK12/13 的非共价双重抑制剂的强效 PROTAC 降解剂PP-C8 ，并证明其对 CDK12 的特异性优于 CDK13。值得注意的是，PP-C8同时诱导细胞周期蛋白 K 的深度降解并下调 DNA 损伤反应基因的 mRNA 水平。全球蛋白质组学分析显示PP-C8对 CDK12-cyclin K 复合物具有高度选择性。重要的是，PP-C8与 PARP 抑制剂在三阴性乳腺癌
• Synthesis and preliminary investigations into norbornane-based amphiphiles and their self-assembly
  作者：Jennifer S. Squire、Alessandra Sutti、Grégory Durand、Xavier A. Conlan、Luke C. Henderson

  DOI：10.1039/c3nj00145h

  日期：——

  A range of norbornane based amphiphiles, which possess a rigid ‘kink’ in the centre of amphiphiles, were accessed via a concise four step synthesis. The self-assembly properties of these novel compounds were then investigated and the critical aggregation concentration (CAC), hydrodynamic diameter (DH) by dynamic light scattering (DLS) and their morphology by cryogenic transmission electron microscopy (cryoTEM) and negatively stained transmission electron microscopy (TEM) were determined. These compounds while possessing similar CAC values (50–70 μM) exhibited a wide variety of particle size (60–140 nm) and morphologies, including vesicles, cigar-shaped aggregates and rod-like micelles. Considering the similarities in molecular structure we have proposed that the unique nature of the molecular ‘kink’ is affecting molecular assembly in which subtle changes in molecular structure have large ramifications on aggregate size and morphology.

  一系列基于降冰片烷的表面活性剂，其特点是在表面活性剂中心具有一个刚性的“弯曲”结构，通过简洁的四步合成路线被成功制备。随后研究了这些新型化合物的自组装性质，并测定了临界聚集浓度（CAC）、通过动态光散射（DLS）测得的水动力直径（DH）以及通过冷冻透射电子显微镜（cryoTEM）和负染色透射电子显微镜（TEM）观察到的形态。尽管这些化合物具有相似的CAC值（50-70 μM），但它们表现出广泛的粒径（60-140 nm）和形态多样性，包括囊泡、雪茄形聚集物和棒状胶束。考虑到分子结构的相似性，我们提出分子“弯曲”的独特性质正在影响分子组装，其中分子结构的微妙变化对聚集物的大小和形态产生了重大影响。
• Modular synthesis of supramolecular ureidopyrimidinone–peptide conjugates using an oxime ligation strategy
  作者：Roxanne E. Kieltyka、Maartje M. C. Bastings、Geert C. van Almen、Pol Besenius、Erwin W. L. Kemps、Patricia Y. W. Dankers

  DOI：10.1039/c1cc14728e

  日期：——

  A convenient method to prepare supramolecular bioconjugates in a facile and scalable manner is by a modular approach, whereby self-assembling units and peptides are coupled using oxime chemistry. We here report syntheses of bioactive ureidopyrimidinone-based peptide conjugates, and their resultant self-assembly into fibrous structures.

  以简便且可扩展的方式制备超分子生物缀合物的简便方法是通过模块化方法，其中自组装单元和肽是使用肟化学方法偶联的。我们在这里报告了基于生物活性脲基嘧啶酮的肽共轭物的合成，以及它们由此产生的自组装成纤维结构。
• UREIDOPYRIMIDONE SUPRAMOLECULAR COMPLEXES FOR COMPOUND DELIVERY INTO CELLS
  申请人：TU Eindhoven

  公开号：US20170233745A1

  公开（公告）日：2017-08-17

  The present invention is directed to particle comprising a supramolecular complex comprising a monofunctional and/or a bifunctional subunit comprising a quadruple hydrogen bonding unit, an apolar linker, an urea group, and a polyethyleneglycol linker. The monofunctional subunits comprise a functional group. The particles are very suitable as drug delivery system as they bind and enter the cell and may have slow release properties.
• Solid-Phase-Based Synthesis of Ureidopyrimidinone–Peptide Conjugates­ for Supramolecular Biomaterials
  作者：Patricia Dankers、Isja de Feijter、Olga Goor、Simone Hendrikse、Marta Comellas-Aragonès、Serge Söntjens、Sabrina Zaccaria、Peter Fransen、Joris Peeters、Lech-Gustav Milroy

  DOI：10.1055/s-0035-1560520

  日期：——

  Supramolecular polymers have shown to be powerful scaffolds for tissue engineering applications. Supramolecular biomaterials functionalized with ureidopyrimidinone (UPy) moieties, which dimerize via quadruple hydrogen-bond formation, are eminently suitable for this purpose. The conjugation of the UPy moiety to biologically active peptides ensures adequate integration into the supramolecular UPy polymer matrix. The structural complexity of UPy-peptide conjugates makes their synthesis challenging and until recently low yielding, thus restricted the access to structurally diverse derivatives. Here we report optimization studies of a convergent solid-phase based synthesis of UPy-modified peptides. The peptide moiety is synthesized using standard Fmoc solid-phase synthesis and the UPy fragment is introduced on the solid-phase simplifying the synthesis and purification of the final UPy-peptide conjugate. The convergent nature of the synthesis reduces the number of synthetic steps in the longest linear sequence compared to other synthetic approaches. We demonstrate the utility of the optimized route by synthesizing a diverse range of biologically active UPy-peptide bioconjugates in multimilligram scale for diverse biomaterial applications. 1 Introduction 2 Divergent Synthesis 3 Convergent Synthesis 4 UPy-Amine Strategy 5 UPy-Carboxylic Acid Strategy 6 Conclusion