methyl hydrogen <<1(R)-1-N-<(phenylmethoxy)carbonyl>amino>-2-phenylethyl>phosphonate | 107133-12-0

• 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 hydrogen <<1(R)-1-N-<(phenylmethoxy)carbonyl>amino>-2-phenylethyl>phosphonate
• 英文别名: Methyl (R)-<1-<(benzyloxycarbonyl)amino>-2-phenylethyl>phosphonic acid；methoxy-[(1R)-2-phenyl-1-(phenylmethoxycarbonylamino)ethyl]phosphinic acid
• CAS: 107133-12-0
• 化学式: C₁₇H₂₀NO₅P
• 分子量: 349.323
• InChiKey: GGRXVPXKGGKIHB-MRXNPFEDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  24
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  methyl hydrogen <<1(R)-1-N-<(phenylmethoxy)carbonyl>amino>-2-phenylethyl>phosphonate 在 palladium dihydroxide 4-二甲氨基吡啶 、 氯化亚砜 、 氢气 、 三乙胺 作用下， 以 乙醇 、 二氯甲烷 、 乙腈 、 苯 为溶剂， 反应 22.5h， 生成 3-pyridin-4-ylpropyl (2S)-2-[methoxy-[(1R)-2-phenyl-1-[[(2R)-2-[[2-(phenylmethoxycarbonylamino)acetyl]amino]propanoyl]amino]ethyl]phosphoryl]oxy-3-phenylpropanoate
  参考文献：
  名称：

  Transition State Analogy of Phosphonic Acid Peptide Inhibitors of Pepsin

  摘要：

  A series of 11 phosphonate peptide analogs, RO(2)C-Xaa-Yaa-Phe-(PO2--O)-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P-2 position, the K-i values correlate with the K-m/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P-2-P-4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P-2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (lie).

  DOI：

  10.1021/jo952074c
• 作为产物：
  描述：

  ((R)-1-Benzyloxycarbonylamino-2-phenyl-ethyl)-phosphonic acid dimethyl ester 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以82%的产率得到methyl hydrogen <<1(R)-1-N-<(phenylmethoxy)carbonyl>amino>-2-phenylethyl>phosphonate
  参考文献：
  名称：

  Synthesis of five enantiomerically pure haptens designed for in vitro evolution of antibodies with peptidase activity

  摘要：

  A series of five haptens have been synthesized for use in in vitro selection experiments from combinatorial antibody libraries. Haptens were designed for the recruitment of serine and cysteine protease reaction mechanisms for the cleavage of Phe-Ala and Phe-Phe (L,L) dipeptide analogues. For the selection of transition state stabilization, Phe(P)(O)Ala (7) and PheP(O)Phe (10) derivatives were synthesized using the Mitsunobu approach where Phe(P) represents the phosphonic acid analogue of phenylalanine and (O)Phe and (O)Ala represent (L)-beta-phenyllactic and (L)-lactic acid, respectively. Optically pure peptidyl diazomethyl ketones 16 and 22 were synthesized for selection of the catalytic ensemble of cysteine proteases. An optically pure dipeptidyl boronic acid 26 was synthesized for the selection of the catalytic ensemble of serine proteases. A strategy for the evolution of catalytic antibodies using these haptens was developed which includes mechanism-based selections. Since mechanism based selections result in covalent trapping of species from libraries, diol and disulfide containing haptenic linkers were developed for the oxidative or reductive release of selected catalysts. Copyright 1O 1996 Elsevier Science Ltd

  DOI：

  10.1016/0968-0896(96)00085-5

文献信息

• (1H-Benzotriazol-1-yloxy)tris(dimethylamino)phosphonium Hexafluorophosphate- and (1H-Benzotriazol-1-yloxy)tripyrrolidinophosphonium Hexafluorophosphate-Mediated Activation of Monophosphonate Esters: Synthesis of Mixed Phosphonate Diesters, the Reactivity of the Benzotriazolyl Phosphonic Esters vs the Reactivity of the Benzotriazolyl Carboxylic Esters
  作者：Jean-Marc Campagne、Jacques Coste、Patrick Jouin

  DOI：10.1021/jo00121a045

  日期：1995.8

  A general method for synthesizing mixed phosphonate diesters from monoesters using (1H-benzotriazol-1-yloxy)tris(dimethylamino) hexafluorophosphate or (1H-benzotriazol-1-yloxy)tripyrrolidinophosphonium hexafluorophosphate reagents is described. The reaction proceeded through a benzotriazolyl ester as shown by comparison with other reagents such as DCC, DCC/DMAP, DCC/1-hydroxybenzotriazole, bromotris(dimethylamino)phosphonium hexafluorophosphate, or O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate and by P-31 NMR analysis. This benzotriazolyl phosphonic ester intermediate was more reactive toward alcohols than toward amines, contrary to its carboxylic analogue.
• Synthesis of five enantiomerically pure haptens designed for in vitro evolution of antibodies with peptidase activity
  作者：Jürgen Wagner、Richard A. Lerner、Carlos F. Barbas

  DOI：10.1016/0968-0896(96)00085-5

  日期：1996.6

  A series of five haptens have been synthesized for use in in vitro selection experiments from combinatorial antibody libraries. Haptens were designed for the recruitment of serine and cysteine protease reaction mechanisms for the cleavage of Phe-Ala and Phe-Phe (L,L) dipeptide analogues. For the selection of transition state stabilization, Phe(P)(O)Ala (7) and PheP(O)Phe (10) derivatives were synthesized using the Mitsunobu approach where Phe(P) represents the phosphonic acid analogue of phenylalanine and (O)Phe and (O)Ala represent (L)-beta-phenyllactic and (L)-lactic acid, respectively. Optically pure peptidyl diazomethyl ketones 16 and 22 were synthesized for selection of the catalytic ensemble of cysteine proteases. An optically pure dipeptidyl boronic acid 26 was synthesized for the selection of the catalytic ensemble of serine proteases. A strategy for the evolution of catalytic antibodies using these haptens was developed which includes mechanism-based selections. Since mechanism based selections result in covalent trapping of species from libraries, diol and disulfide containing haptenic linkers were developed for the oxidative or reductive release of selected catalysts. Copyright 1O 1996 Elsevier Science Ltd
• Transition State Analogy of Phosphonic Acid Peptide Inhibitors of Pepsin
  作者：Paul A. Bartlett、Mark A. Giangiordano

  DOI：10.1021/jo952074c

  日期：1996.1.1

  A series of 11 phosphonate peptide analogs, RO(2)C-Xaa-Yaa-Phe-(PO2--O)-Phe O-(3-(4-pyridyl)propyl ester), were synthesized and evaluated as inhibitors of the aspartic peptidase pepsin. For the inhibitors with Gly or Ala at the P-2 position, the K-i values correlate with the K-m/k(cat) values of the corresponding substrates, demonstrating that these analogs mimic the transition state in the way the P-2-P-4 residues bind. Deviations from the correlation for the other inhibitor/substrate pairs imply a different binding orientation as a result of N-substitution at P-2 (Pro), contamination with the more potent diastereomer (D-Ala), or a change in rate-limiting step for turnover (lie).