((5S,8R)-5-Isopropyl-3,6-dioxo-4,7-diaza-tricyclo[8.6.2.013,17]octadeca-1(16),10(18),11,13(17),14-pentaen-8-yl)-phosphonic acid dimethyl ester | 208169-49-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 大环内酰胺类
• 英文名称: ((5S,8R)-5-Isopropyl-3,6-dioxo-4,7-diaza-tricyclo[8.6.2.013,17]octadeca-1(16),10(18),11,13(17),14-pentaen-8-yl)-phosphonic acid dimethyl ester
• CAS: 208169-49-7
• 化学式: C₂₁H₂₇N₂O₅P
• 分子量: 418.43
• InChiKey: ZWRGPFHWJDVQKB-UXHICEINSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.01
• 重原子数：
  29.0
• 可旋转键数：
  4.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  93.73
• 氢给体数：
  2.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  ((5S,8R)-5-Isopropyl-3,6-dioxo-4,7-diaza-tricyclo[8.6.2.013,17]octadeca-1(16),10(18),11,13(17),14-pentaen-8-yl)-phosphonic acid dimethyl ester 在 lithium hydroxide 作用下， 以 二甲基亚砜 为溶剂， 反应 20.0h， 以96%的产率得到[(5S,8R)-3,6-dioxo-5-propan-2-yl-4,7-diazatricyclo[8.6.2.013,17]octadeca-1(16),10(18),11,13(17),14-pentaen-8-yl]-methoxyphosphinic acid
  参考文献：
  名称：

  Macrocyclic Inhibitors of Penicillopepsin. 1. Design, Synthesis, and Evaluation of an Inhibitor Bridged between P1 and P3

  摘要：

  The macrocyclic peptidyl phosphonate 1-L was designed on the basis of the conformation of an acyclic analogue (4) bound to the aspartic protease penicillopepsin. This material and the two acyclic comparison compounds 2-L and 3 were synthesized and evaluated as inhibitors; their binding affinity was found to be inversely related to the degree of conformational flexibility across the series: 3 (K-i = 110 mu M), 2-L (K-i = 7.6 mu M), 1-L (K-i = 0.80 mu M). NMR methods in conjunction with molecular modeling were used to assign the stereochemical configurations of the precursor 16-L and its diastereomer 16-D and to determine the solution conformations of the macrocyclic ring systems. The conformation of the peptide backbone in 1-L closely approximates that desired for a mimic of the lead inhibitor 4, and it appears that the low-energy conformation of 1-L can be accommodated in the pencillopepsin active site without significant distortion.

  DOI：

  10.1021/ja973715j
• 作为产物：
  描述：

  [7-(2,3-Dihydroxy-propyl)-naphthalen-1-yl]-acetic acid ethyl ester 在 palladium on activated charcoal 吡啶 、 lithium hydroxide 、 sodium periodate 、 氢气 、 potassium carbonate 、 1-羟基苯并三唑 、 溶剂黄146 、 1-(3-二甲基氨基丙基)-3-乙基碳二亚胺 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 1,4-二氧六环 、 甲醇 、 乙醚 、 二氯甲烷 、 1,2-二氯乙烷 为溶剂， 反应 23.25h， 生成 ((5S,8R)-5-Isopropyl-3,6-dioxo-4,7-diaza-tricyclo[8.6.2.013,17]octadeca-1(16),10(18),11,13(17),14-pentaen-8-yl)-phosphonic acid dimethyl ester
  参考文献：
  名称：

  Macrocyclic Inhibitors of Penicillopepsin. 1. Design, Synthesis, and Evaluation of an Inhibitor Bridged between P1 and P3

  摘要：

  The macrocyclic peptidyl phosphonate 1-L was designed on the basis of the conformation of an acyclic analogue (4) bound to the aspartic protease penicillopepsin. This material and the two acyclic comparison compounds 2-L and 3 were synthesized and evaluated as inhibitors; their binding affinity was found to be inversely related to the degree of conformational flexibility across the series: 3 (K-i = 110 mu M), 2-L (K-i = 7.6 mu M), 1-L (K-i = 0.80 mu M). NMR methods in conjunction with molecular modeling were used to assign the stereochemical configurations of the precursor 16-L and its diastereomer 16-D and to determine the solution conformations of the macrocyclic ring systems. The conformation of the peptide backbone in 1-L closely approximates that desired for a mimic of the lead inhibitor 4, and it appears that the low-energy conformation of 1-L can be accommodated in the pencillopepsin active site without significant distortion.

  DOI：

  10.1021/ja973715j