[[2-(6-Benzyloxycarbonylamino-purin-9-yl)-acetyl]-((1S,2S)-2-tert-butoxycarbonylamino-cyclohexyl)-amino]-acetic acid ethyl ester | 193621-92-0

• 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: [[2-(6-Benzyloxycarbonylamino-purin-9-yl)-acetyl]-((1S,2S)-2-tert-butoxycarbonylamino-cyclohexyl)-amino]-acetic acid ethyl ester
• CAS: 193621-92-0
• 化学式: C₃₀H₃₉N₇O₇
• 分子量: 609.682
• InChiKey: MLCOYFCANMMIFY-VXKWHMMOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  44.0
• 可旋转键数：
  10.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  166.87
• 氢给体数：
  2.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  [[2-(6-Benzyloxycarbonylamino-purin-9-yl)-acetyl]-((1S,2S)-2-tert-butoxycarbonylamino-cyclohexyl)-amino]-acetic acid ethyl ester 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以58%的产率得到
  参考文献：
  名称：

  Peptide Nucleic Acids with a Conformationally Constrained Chiral Cyclohexyl-Derived Backbone

  摘要：

  AbstractPeptide nucleic acid (PNA) is an achiral nucleic acid mimic with a backbone consisting of partly flexible aminoethyl glycine units. By replacing the aminoethyl portion of the backbone by an amino cyclohexyl moiety, either in the (S, S) or the (R, R) configuration, we have synthesized conformationally constrained PNA residues. PNA oligomers containing (S, S)‐cyclohexyl residues were able to form hybrid complexes with DNA or RNA, with little effect on the thermal stability (Tm = 1°C per (S, S) unit, depending on their number and the sequence). In contrast, incorporation of the (R, R) isomer resulted in a drastic decrease in the stability of the PNA‐DNA (or RNA) complex (Tm = −8°C per (R, R) unit). In PNA‐PNA duplexes, however, the (R, R)‐ and (S, S)‐cyclohexyl residues only exerted a minor effect on the stability, and the complexes formed with the two isomers are of opposite handedness, as evidenced from circular dichroism spectroscopy. In some cases the introduction of a single (S, S) residue in a PNA 15‐mer improves its sequence specificity for DNA or RNA. From the thermal stabilities and molecular modeling based on the solution structure of a PNA‐DNA duplex determined by NMR techniques, we conclude that the right‐handed helix can accommodate the (S, S) isomer more easily than the (R, R) isomer. Thermodynamic measurements of H and S upon PNA‐DNA duplex formation show that the introduction of an (S, S)‐cyclohexyl unit in the PNA does indeed decrease the entropy loss, indicating a more conformationally constrained structure. However, the more favorable entropic contribution is balanced by a reduced enthalpic gain, indicating that the structure constrained by the cyclohexyl group is not so well suited for DNA hybridization.

  DOI：

  10.1002/chem.19970030613
• 作为产物：
  描述：

  (1S,2S)-BOC-1,2-环己二胺 在 potassium carbonate 、 3-羟基-1,2,3-苯并三嗪-4(3H)-酮 、 N,N'-二环己基碳二亚胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 6.0h， 生成 [[2-(6-Benzyloxycarbonylamino-purin-9-yl)-acetyl]-((1S,2S)-2-tert-butoxycarbonylamino-cyclohexyl)-amino]-acetic acid ethyl ester
  参考文献：
  名称：

  Peptide Nucleic Acids with a Conformationally Constrained Chiral Cyclohexyl-Derived Backbone

  摘要：

  AbstractPeptide nucleic acid (PNA) is an achiral nucleic acid mimic with a backbone consisting of partly flexible aminoethyl glycine units. By replacing the aminoethyl portion of the backbone by an amino cyclohexyl moiety, either in the (S, S) or the (R, R) configuration, we have synthesized conformationally constrained PNA residues. PNA oligomers containing (S, S)‐cyclohexyl residues were able to form hybrid complexes with DNA or RNA, with little effect on the thermal stability (Tm = 1°C per (S, S) unit, depending on their number and the sequence). In contrast, incorporation of the (R, R) isomer resulted in a drastic decrease in the stability of the PNA‐DNA (or RNA) complex (Tm = −8°C per (R, R) unit). In PNA‐PNA duplexes, however, the (R, R)‐ and (S, S)‐cyclohexyl residues only exerted a minor effect on the stability, and the complexes formed with the two isomers are of opposite handedness, as evidenced from circular dichroism spectroscopy. In some cases the introduction of a single (S, S) residue in a PNA 15‐mer improves its sequence specificity for DNA or RNA. From the thermal stabilities and molecular modeling based on the solution structure of a PNA‐DNA duplex determined by NMR techniques, we conclude that the right‐handed helix can accommodate the (S, S) isomer more easily than the (R, R) isomer. Thermodynamic measurements of H and S upon PNA‐DNA duplex formation show that the introduction of an (S, S)‐cyclohexyl unit in the PNA does indeed decrease the entropy loss, indicating a more conformationally constrained structure. However, the more favorable entropic contribution is balanced by a reduced enthalpic gain, indicating that the structure constrained by the cyclohexyl group is not so well suited for DNA hybridization.

  DOI：

  10.1002/chem.19970030613