S-methyl 1-[(3R,4R)-1-benzyl-4-tosylamidopiperidin-3-yl]pyrrolidine-2-carboxylate | 1579997-45-7

• 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: S-methyl 1-[(3R,4R)-1-benzyl-4-tosylamidopiperidin-3-yl]pyrrolidine-2-carboxylate
• 英文别名: methyl (2S)-1-[(3R,4R)-1-benzyl-4-[(4-methylphenyl)sulfonylamino]piperidin-3-yl]pyrrolidine-2-carboxylate
• CAS: 1579997-45-7
• 化学式: C₂₅H₃₃N₃O₄S
• 分子量: 471.621
• InChiKey: VHFLZUKKCISVLH-TZRRMPRUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.5
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  87.3
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  S-methyl 1-[(3R,4R)-1-benzyl-4-tosylamidopiperidin-3-yl]pyrrolidine-2-carboxylate 在 哌啶 、 4-二甲氨基吡啶 、 (1-cyano-2-ethoxy-2-oxoethylidenaminooxy)dimethylaminomorpholinocarbenium hexafluorophosphate 、 palladium 10% on activated carbon 、 氢气 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 N,N-二异丙基乙胺 、 2-肟氰乙酸乙酯 、 sodium hydroxide 作用下， 以 甲醇 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 35.5h， 生成
  参考文献：
  名称：

  Composition and Conformation of Hetero‐ versus Homo‐Fluorinated Triazolamers Influence their Activity on Islet Amyloid Polypeptide Aggregation

  摘要：

  Novel fluorinated foldamers based on aminomethyl‐1,4‐triazolyl‐difluoroacetic acid (1,4‐Tz−CF2) units were synthesized and their conformational behaviour was studied by NMR and molecular dynamics. Their activity on the aggregation of the human islet amyloid polypeptide (hIAPP) amyloid protein was evaluated by fluorescence spectroscopy and mass spectrometry. The fluorine labelling of these foldamers allowed the analysis of their interaction with the target protein. We demonstrated that the preferred extended conformation of homotriazolamers of 1,4‐Tz−CF2 unit increases the aggregation of hIAPP, while the hairpin‐like conformation of more flexible heterotriazolamers containing two 1,4‐Tz−CF2 units mixed with natural amino acids from the hIAPP sequence reduces it, and more efficiently than the parent natural peptide. The longer heterotriazolamers having three 1,4‐Tz−CF2 units adopting more folded hairpin‐like and ladder‐like structures similar to short multi‐stranded β‐sheets have no effect. This work demonstrates that a good balance between the structuring and flexibility of these foldamers is necessary to allow efficient interaction with the target protein.

  DOI：

  10.1002/chem.202303887
• 作为产物：
  描述：

  对甲苯磺酰叠氮 、 L-脯氨酸甲酯盐酸盐 、 N-苄基哌啶酮 在 三乙胺 作用下， 以 1,2-二氯乙烷 为溶剂， 反应 0.75h， 以30%的产率得到S-methyl 1-[(3R,4R)-1-benzyl-4-tosylamidopiperidin-3-yl]pyrrolidine-2-carboxylate
  参考文献：
  名称：

  Asymmetric Modular Synthesis of a Semirigid Dipeptide Mimetic by Cascade Cycloaddition/Ring Rearrangement and Borohydride Reduction

  摘要：

  A new semirigid dipeptide mimetic was prepared on multigram scale, in good yield, and in a stereocontrolled way, starting from commercially available and unexpensive reagents, i.e., N-benzylpiperidone, tosyl azide, and proline methyl ester. The optimized multicomponent process consisted of a cascade click cycloaddition and a ring rearrangement reaction, followed by a reductive step. Theoretical calculations were performed to elucidate the reaction mechanism and support the stereochemical outcome of the reduction. Finally, the new scaffold was used for the preparation of model peptidomimetics, whose beta turn conformation was confirmed by dynamic NMR experiments.

  DOI：

  10.1021/jo500237j