N-[benzyloxy(phenyl)phosphinyl]-L-glutamic acid dibenzyl ester | 200941-05-5

• 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: N-[benzyloxy(phenyl)phosphinyl]-L-glutamic acid dibenzyl ester
• 英文别名: dibenzyl (2S)-2-[(oxido-phenyl-phenylmethoxyphosphaniumyl)amino]pentanedioate
• CAS: 200941-05-5
• 化学式: C₃₂H₃₂NO₆P
• 分子量: 557.583
• InChiKey: BCPHZSWLVJMTCR-AYLNDXQWSA-N

物化性质

• 沸点：
  677.855±65.00 °C(Press: 760.00 Torr)(predicted)
• 密度：
  1.257±0.10 g/cm3(Temp: 25 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  40
• 可旋转键数：
  16
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  96.9
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-[benzyloxy(phenyl)phosphinyl]-L-glutamic acid dibenzyl ester 在 palladium on activated charcoal 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以100%的产率得到N-[hydroxy(phenyl)phosphinyl]-L-glutamic acid tripotassium salt
  参考文献：
  名称：

  Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates

  摘要：

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.06.031
• 作为产物：
  描述：

  苯膦酰二氯 在 四氮唑 、 二乙醇胺 作用下， 生成 N-[benzyloxy(phenyl)phosphinyl]-L-glutamic acid dibenzyl ester
  参考文献：
  名称：

  Evaluation of phosphorus-containing inhibitors of γ-glutamyl hydrolase

  摘要：

  Several putative, phosphorus-containing inhibitors of gamma-glutamyl hydrolase were synthesized and evaluated for inhibitory activity. The phosphonamidoic acids were shown to be weak competitive inhibitors while both a phosphoramidate diester and a phosphonamidate ester were shown to be potent time-dependent inactivators, presumably through irreversible phosphorylation of an active site nucleophile. (C) 1998 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0960-894x(98)00253-4

文献信息

• A convenient two-step one-pot synthesis of phosphonamidates
  作者：Karyn L. Mlodnosky、H. Michael Holmes、Vinh Q. Lam、Clifford E. Perkman

  DOI：10.1016/s0040-4039(97)10421-x

  日期：1997.12

  Phosphonamidates are formed in high yield from a one-pot sequential reaction of a phosphonyl dichloride with an alcohol and then an amine in the presence of catalytic 1H-tetrazole. Undesired disubstitution of the phoshphonyl dichloride by the alcohol or the amine is minimal due to the presence of tetrazole. (C) 1997 Elsevier Science Ltd.
• Evaluation of phosphorus-containing inhibitors of γ-glutamyl hydrolase
  作者：Chester E. Rodriguez、H. Michael Holmes、Karyn L. Mlodnosky、Vinh Q. Lam、Clifford E. Berkman

  DOI：10.1016/s0960-894x(98)00253-4

  日期：1998.6

  Several putative, phosphorus-containing inhibitors of gamma-glutamyl hydrolase were synthesized and evaluated for inhibitory activity. The phosphonamidoic acids were shown to be weak competitive inhibitors while both a phosphoramidate diester and a phosphonamidate ester were shown to be potent time-dependent inactivators, presumably through irreversible phosphorylation of an active site nucleophile. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Probing for a hydrophobic a binding register in prostate-specific membrane antigen with phenylalkylphosphonamidates
  作者：Jack Maung、Jeremy P. Mallari、Teri A. Girtsman、Lisa Y. Wu、Jennifer A. Rowley、Nicholas M. Santiago、Alan N. Brunelle、Clifford E. Berkman

  DOI：10.1016/j.bmc.2004.06.031

  日期：2004.9

  To explore for the existence of an auxiliary hydrophobic binding register remote from the active site of PSMA a series of phenylalkylphosphonamidate derivatives of glutamic acid were synthesized and evaluated for their inhibitory potencies against PSMA. Both the phenyl- and benzylphosphonamidates (1a and 1b) exhibited only modest inhibitory potency against. The phenethyl analog 1c was intermediate in inhibitory potency while inhibitors possessing a longer alkyl tether from the phenyl ring, resulted in markedly improved K-i values. The greatest inhibitory potency was obtained for the inhibitors in which the phenyl ring was extended furthest from the central phosphorus (if, n = 5 and I g, n = 6). The slightly serrated pattern that emerged as the alkyl tether increased from three to six methylene units suggests that inhibitory potency is not simply correlated to increased hydrophobicity imparted by the phenylalkyl chain, but rather that one or more hydrophobic binding registers may exist remote from the substrate recognition architecture in the active site of PSMA. (C) 2004 Elsevier Ltd. All rights reserved.