(S)-2-[((R)-1-Benzyloxycarbonylamino-3-methyl-butyl)-methoxy-phosphinoyloxy]-3-phenyl-propionic acid methyl ester | 208046-11-1

• 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: (S)-2-[((R)-1-Benzyloxycarbonylamino-3-methyl-butyl)-methoxy-phosphinoyloxy]-3-phenyl-propionic acid methyl ester
• CAS: 208046-11-1
• 化学式: C₂₄H₃₂NO₇P
• 分子量: 477.494
• InChiKey: ZBZHTBSUHNLGEW-UAOJNWESSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.93
• 重原子数：
  33.0
• 可旋转键数：
  12.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  100.16
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  (S)-2-[((R)-1-Benzyloxycarbonylamino-3-methyl-butyl)-methoxy-phosphinoyloxy]-3-phenyl-propionic acid methyl ester 在 palladium on activated charcoal N-甲基吗啉 、 氢气 、 氯甲酸异丁酯 作用下， 以 乙酸乙酯 为溶剂， 生成 (S)-2-[Methoxy-((R)-3-methyl-1-{(S)-3-methyl-2-[(R)-3-methyl-2-(3-methyl-butyrylamino)-butyrylamino]-butyrylamino}-butyl)-phosphinoyloxy]-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogs

  摘要：

  Phosphinic and phosphonic acid peptide derivatives have been evaluated as inhibitors of the aspartic proteases pepsin and penicillopepsin. The most potent of those studied is isovaleryl-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe (4) (Leu(P) represents the phosphonic acid analogue of leucine; (O)Phe represents L-beta-phenyllactic acid, the alcohol analogue of phenylalanine), for which the K(i) values for pepsin and penicillopepsin are 0.26 and 0.19 nM, respectively. While this compound binds to penicillopepsin with an association rate constant, k(on), of (6.5 +/- 1.5) X 10(5) M(-1) s(-1), it does not show slow- or two-step binding with pepsin. The binding of Cbz-Ala-Ala-Leu(P)-(O)Phe-OMe (1) to penicillopepsin is strongly dependent on pH: in comparison to pH 4.5, the affinity at pH 3.5 is increased 10-fold and at pH 5.5 it is decreased 40-fold. The two diastereomers of a nonionic phosphinamide analogue (10A, 10B) of a statine-containing inhibitor were prepared; however, both are significantly weaker inhibitors of pepsin than the phosphinic acid itself (7).

  DOI：

  10.1021/jo00313a012
• 作为产物：
  描述：

  氯甲酸苄酯 在 sodium hydroxide 、 氯化亚砜 、 碳酸氢钠 、 sodium carbonate 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 25.0h， 生成 (S)-2-[((R)-1-Benzyloxycarbonylamino-3-methyl-butyl)-methoxy-phosphinoyloxy]-3-phenyl-propionic acid methyl ester
  参考文献：
  名称：

  Potent inhibition of pepsin and penicillopepsin by phosphorus-containing peptide analogs

  摘要：

  Phosphinic and phosphonic acid peptide derivatives have been evaluated as inhibitors of the aspartic proteases pepsin and penicillopepsin. The most potent of those studied is isovaleryl-Val-Val-Leu(P)-(O)Phe-Ala-Ala-OMe (4) (Leu(P) represents the phosphonic acid analogue of leucine; (O)Phe represents L-beta-phenyllactic acid, the alcohol analogue of phenylalanine), for which the K(i) values for pepsin and penicillopepsin are 0.26 and 0.19 nM, respectively. While this compound binds to penicillopepsin with an association rate constant, k(on), of (6.5 +/- 1.5) X 10(5) M(-1) s(-1), it does not show slow- or two-step binding with pepsin. The binding of Cbz-Ala-Ala-Leu(P)-(O)Phe-OMe (1) to penicillopepsin is strongly dependent on pH: in comparison to pH 4.5, the affinity at pH 3.5 is increased 10-fold and at pH 5.5 it is decreased 40-fold. The two diastereomers of a nonionic phosphinamide analogue (10A, 10B) of a statine-containing inhibitor were prepared; however, both are significantly weaker inhibitors of pepsin than the phosphinic acid itself (7).

  DOI：

  10.1021/jo00313a012