methyl O-<<<(carbobenzoxyamino)methyl>methoxyphosphinyl>-L-leucyl>-(S)-2-hydroxy-3-phenylpropanoate | 131066-60-9

• 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: methyl O-<<<(carbobenzoxyamino)methyl>methoxyphosphinyl>-L-leucyl>-(S)-2-hydroxy-3-phenylpropanoate
• 英文别名: methyl O-({[(carbobenzoxyamino)methyl]methoxyphosphinyl}-L-leucyl)-(S)-2-hydroxy-3-phenylpropanoate；[(2S)-1-methoxy-1-oxo-3-phenylpropan-2-yl] (2S)-2-[[methoxy(phenylmethoxycarbonylaminomethyl)phosphoryl]amino]-4-methylpentanoate
• CAS: 131066-60-9
• 化学式: C₂₆H₃₅N₂O₈P
• 分子量: 534.546
• InChiKey: OTIXJSBWWXDRHX-LCDSEGRYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.04
• 重原子数：
  37.0
• 可旋转键数：
  14.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  129.26
• 氢给体数：
  2.0
• 氢受体数：
  8.0

反应信息

• 作为反应物：
  描述：

  methyl O-<<<(carbobenzoxyamino)methyl>methoxyphosphinyl>-L-leucyl>-(S)-2-hydroxy-3-phenylpropanoate 在 lithium hydroxide 作用下， 以 四氢呋喃 为溶剂， 反应 24.0h， 生成 (2S)-2-[(2S)-2-[[hydroxy(phenylmethoxycarbonylaminomethyl)phosphoryl]amino]-4-methylpentanoyl]oxy-3-phenylpropanoic acid
  参考文献：
  名称：

  Differential binding energy: a detailed evaluation of the influence of hydrogen-bonding and hydrophobic groups on the inhibition of thermolysin by phosphorus-containing inhibitors

  摘要：

  Two series of phosphorus-containing peptide analogues, 3 (Cbz-Gly-psi(PO2-CH2)Leu-Xaa) and 4 (Cbz-Gly-psi-(PO2-NH)Leu-psi[CO2]Xaa), have been synthesized and evaluated as inhibitors of the zinc endopeptidase thermolysin. In comparison with the previously reported phosphonamidates 1, the phosphinates 3 lose only 0.1 kcal/mol in binding affinity, whereas the depsipeptides 4 are bound 2.7 kcal/mol more weakly; these values are contrasted to the 4.0 kcal/mol reduction in binding affinity observed for the phosphonates 2 (Cbz-Gly-psi(PO2-O)Leu-Xaa) in comparison to 1 (Cbz-Gly-psi(PO2-NH)Leu-Xaa). The observed effects are interpreted through consideration of the differences in active-site and solvent interactions. For the comparison between the diamides 1 and the depsipeptides 4, a full accounting of the balance between these interactions can be approached. The arylphosphonates 5 (Aryl-psi(PO2-O)Leu-Leu) were synthesized and evaluated to investigate the importance of phosphonate basicity on the overall binding affinity of these zinc-coordinating inhibitors; the inhibitor K(i) values were found to be independent of phosphonate p(K)a, indicating that the basicity of the phosphonate moiety exerts counterbalancing effects on the energies of zinc coordination and solvation. For analysis of the influence of structural variations on observed affinity, the definition of "differential binding energy" is introduced as a practical alternative to the concept of "intrinsic binding energy".

  DOI：

  10.1021/ja00001a043
• 作为产物：
  描述：

  methyl <(N-carbobenzoxyamino)methyl>phosphonic acid 在 氯化亚砜 、 4 A molecular sieve 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 51.5h， 生成 methyl O-<<<(carbobenzoxyamino)methyl>methoxyphosphinyl>-L-leucyl>-(S)-2-hydroxy-3-phenylpropanoate
  参考文献：
  名称：

  Differential binding energy: a detailed evaluation of the influence of hydrogen-bonding and hydrophobic groups on the inhibition of thermolysin by phosphorus-containing inhibitors

  摘要：

  Two series of phosphorus-containing peptide analogues, 3 (Cbz-Gly-psi(PO2-CH2)Leu-Xaa) and 4 (Cbz-Gly-psi-(PO2-NH)Leu-psi[CO2]Xaa), have been synthesized and evaluated as inhibitors of the zinc endopeptidase thermolysin. In comparison with the previously reported phosphonamidates 1, the phosphinates 3 lose only 0.1 kcal/mol in binding affinity, whereas the depsipeptides 4 are bound 2.7 kcal/mol more weakly; these values are contrasted to the 4.0 kcal/mol reduction in binding affinity observed for the phosphonates 2 (Cbz-Gly-psi(PO2-O)Leu-Xaa) in comparison to 1 (Cbz-Gly-psi(PO2-NH)Leu-Xaa). The observed effects are interpreted through consideration of the differences in active-site and solvent interactions. For the comparison between the diamides 1 and the depsipeptides 4, a full accounting of the balance between these interactions can be approached. The arylphosphonates 5 (Aryl-psi(PO2-O)Leu-Leu) were synthesized and evaluated to investigate the importance of phosphonate basicity on the overall binding affinity of these zinc-coordinating inhibitors; the inhibitor K(i) values were found to be independent of phosphonate p(K)a, indicating that the basicity of the phosphonate moiety exerts counterbalancing effects on the energies of zinc coordination and solvation. For analysis of the influence of structural variations on observed affinity, the definition of "differential binding energy" is introduced as a practical alternative to the concept of "intrinsic binding energy".

  DOI：

  10.1021/ja00001a043