2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylic acid N-methoxycarbonylethyl amide | 316363-48-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 肽模拟物
• 英文名称: 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylic acid N-methoxycarbonylethyl amide
• 英文别名: methyl 3-((1R,2S)-2-(benzyloxycarbonylamino)cyclobutanecarboxamido)propanoate；methyl 3-[[(1R,2S)-2-(phenylmethoxycarbonylamino)cyclobutanecarbonyl]amino]propanoate
• CAS: 316363-48-1
• 化学式: C₁₇H₂₂N₂O₅
• 分子量: 334.372
• InChiKey: XMPLHWRZWBWHBG-KGLIPLIRSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  24
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  93.7
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylic acid N-methoxycarbonylethyl amide 在 20 % Pd(OH)2/C 、 五氟苯基二苯基磷酸酯 、 氢气 、 N,N-二异丙基乙胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 20.0 ℃ 、709.32 kPa 条件下， 反应 3.0h， 生成 3-[((1R,2S)-2-{3-[((1R,2S)-2-Benzyloxycarbonylamino-cyclobutanecarbonyl)-amino]-propionylamino}-cyclobutanecarbonyl)-amino]-propionic acid methyl ester
  参考文献：
  名称：

  Designing hybrid foldamers: the effect on the peptide conformational bias of β- versus α- and γ-linear residues in alternation with (1R,2S)-2-aminocyclobutane-1-carboxylic acid

  摘要：

  用(1R,2S)-2-氨基环丁烷-1-羧酸、甘氨酸、β-丙氨酸和γ-氨基丁酸分别交替连接而成的几种寡聚体，已通过NMR和CD实验以及计算模拟进行了合成和研究。结果解释了间隔长度对折叠的影响，并表明这些杂合肽的构象偏好可以从含有C2或C4线性段的对β片层样折叠调节为含有C3间隔的环丁烷残基之间的螺旋折叠。在这些残基之间引入环形间隔不会改变之前在多(顺式-环丁烷)β-寡聚体中展现的扩展带状结构。

  DOI：

  10.1039/c1ob06575k
• 作为产物：
  描述：

  methyl 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylate 在 potassium carbonate 、 1-羟基苯并三唑 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 26.0h， 生成 2-benzyloxycarbonylamino-(1R,2S)-cyclobutane-1-carboxylic acid N-methoxycarbonylethyl amide
  参考文献：
  名称：

  Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide

  摘要：

  Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane beta -amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded beta -amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-beta -amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from D-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0957-4166(00)00297-4

文献信息

• 14-Helical Folding in a Cyclobutane-Containing β-Tetrapeptide
  作者：Sandra Izquierdo、Marcelo J. Kogan、Teodor Parella、Albertina G. Moglioni、Vicenç Branchadell、Ernest Giralt、Rosa M. Ortuño

  DOI：10.1021/jo0497555

  日期：2004.7.1

  The efficient synthesis of tetrapeptide 5 containing, in alternation, cyclobutane and beta-alanine residues is described. NMR experiments both at low temperature in CDCl3 and at 298 K in DMSOd(6) solutions show the contribution of a strong hydrogen bond in the folded major conformation of 5. Temperature coefficients and diffusion times point out a hydrogen bond involving the NH proton from the cyclobutane residue 1 whereas NOES manifest the high rigidity of the central fragment of the molecule and are compatible with a 14-membered macrocycle. Theoretical calculations predict a most stable folded conformation corresponding to a 14-helix stabilized by a hydrogen bond between NH10 in the first residue and OC25 in the third residue. This structure remains unaltered during the molecular dynamics simulation at 298 K in chloroform. All these results provide evidence for a 14-helical folding and reveal the ability of cis-2-aminocyclobutane carboxylic acid residues to promote folded conformations when incorporated into beta-peptides.
• Designing hybrid foldamers: the effect on the peptide conformational bias of β- versus α- and γ-linear residues in alternation with (1R,2S)-2-aminocyclobutane-1-carboxylic acid
  作者：Sergio Celis、Esther Gorrea、Pau Nolis、Ona Illa、Rosa M. Ortuño

  DOI：10.1039/c1ob06575k

  日期：——

  Several oligomers constructed with (1R,2S)-2-aminocyclobutane-1-carboxylic acid and glycine, β-alanine, and γ-amino butyric acid (GABA), respectively, joined in alternation have been synthesized and studied by means of NMR and CD experiments as well as with computational calculations. Results account for the spacer length effect on folding and show that conformational preference for these hybrid peptides can be tuned from β-sheet-like folding for those containing a C2 or C4 linear segment to a helical folding for those with a C3 spacer between cyclobutane residues. The introduction of cyclic spacers between these residues does not modify the extended ribbon-type structure previously manifested in poly(cis-cyclobutane) β-oligomers.

  用(1R,2S)-2-氨基环丁烷-1-羧酸、甘氨酸、β-丙氨酸和γ-氨基丁酸分别交替连接而成的几种寡聚体，已通过NMR和CD实验以及计算模拟进行了合成和研究。结果解释了间隔长度对折叠的影响，并表明这些杂合肽的构象偏好可以从含有C2或C4线性段的对β片层样折叠调节为含有C3间隔的环丁烷残基之间的螺旋折叠。在这些残基之间引入环形间隔不会改变之前在多(顺式-环丁烷)β-寡聚体中展现的扩展带状结构。
• Enantioselective synthetic approaches to cyclopropane and cyclobutane β-amino acids: synthesis and structural study of a conformationally constrained β-dipeptide
  作者：Marta Martı́n-Vilà、Elena Muray、Gemma P Aguado、Angel Alvarez-Larena、Vicenç Branchadell、Cristina Minguillón、Ernest Giralt、Rosa M Ortuño

  DOI：10.1016/s0957-4166(00)00297-4

  日期：2000.9

  Synthetic approaches to carbocyclic compounds, namely cyclopropane and cyclobutane beta -amino acids, are presented. One of them is based on enzymatic desymmetrization of meso diesters, leading to the enantioselective production of cis-hemiesters, which afforded beta -amino acids through Curtius rearrangements. The enantiomeric excess for the cyclobutane derivatives was 91% whereas the cyclopropanes were obtained in 63% ee. According to another strategy, an enantiomerically pure cyclopropane trans-beta -amino acid, bearing a quaternary center, has been synthesized from a homochiral precursor easily available from D-glyceraldehyde. The preparation and structural investigation of the first synthesized cyclobutane containing dipeptide is also described. A hairpin-like conformation of this molecule in the solid state has been demonstrated by X-ray structural analysis, showing crystal packing induced by the presence of the rigid cyclobutane moiety and the formation of intermolecular hydrogen bonds. NMR experiments confirmed that these molecules also tend to produce aggregates in solution. On the contrary, theoretical calculations suggest that intramolecular interactions are important in the gas phase, as expected. (C) 2000 Elsevier Science Ltd. All rights reserved.