dimethyl (2S)-(2-tert-butoxycarbonyloamino-1-hydroxy-4-methyl)pentylphosphonate | 214001-83-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: dimethyl (2S)-(2-tert-butoxycarbonyloamino-1-hydroxy-4-methyl)pentylphosphonate
• 英文别名: tert-butyl N-[(2S)-1-dimethoxyphosphoryl-1-hydroxy-4-methylpentan-2-yl]carbamate
• CAS: 214001-83-9
• 化学式: C₁₃H₂₈NO₆P
• 分子量: 325.342
• InChiKey: CUBGYRYOSBNLAX-VUWPPUDQSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.92
• 拓扑面积：
  94.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  dimethyl (2S)-(2-tert-butoxycarbonyloamino-1-hydroxy-4-methyl)pentylphosphonate 在 盐酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 dimethyl (2S)-(2-amino-1-hydroxy-4-methyl)pentylphosphonate hydrochloride
  参考文献：
  名称：

  Novel Peptidyl Phosphorus Derivatives as Inhibitors of Human Calpain I

  摘要：

  Dipeptidyl phosphorus compounds were synthesized as potential bioisosteric mimics of peptide alpha-ketoesters and alpha-ketoacids. alpha-Ketophosphonate Cbz-Leu-Leu-P(O)(OCH3)(2) (1b), containing an alpha-ketoester bioisostere, inhibits human calpain I with an IC50 = 0.43 mu M. The potency of 1b compares very favorably with that of alpha-ketoester Cbz-Leu-Leu-CO2Et (IC50 = 0.60 mu M). Monomethyl ketophosphonate Cbz-Leu-Leu-P(O)(OH)(OCH3) (1a, IC50 = 5.2 mu M), an cl-ketoacid mimic, is less potent. Dibutyl and dibenzyl alpha-ketophosphonates 1c,e,f are much less potent calpain inhibitors than dimethyl alpha-ketophosphonate 1b. alpha-Ketophosphinate 1g (IC50 = 0.37 mu M) and alpha-ketophosphine oxide 1h (IC50 = 0.35 mu M) are also potent calpain inhibitors.

  DOI：

  10.1021/jm980325e
• 作为产物：
  描述：

  2-甲基-2-丙基[(2S)-4-甲基-1-氧代-2-戊烷基]氨基甲酸酯 、 MDL 28170 在 potassium fluoride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 以92%的产率得到dimethyl (2S)-(2-tert-butoxycarbonyloamino-1-hydroxy-4-methyl)pentylphosphonate
  参考文献：
  名称：

  Novel Peptidyl Phosphorus Derivatives as Inhibitors of Human Calpain I

  摘要：

  Dipeptidyl phosphorus compounds were synthesized as potential bioisosteric mimics of peptide alpha-ketoesters and alpha-ketoacids. alpha-Ketophosphonate Cbz-Leu-Leu-P(O)(OCH3)(2) (1b), containing an alpha-ketoester bioisostere, inhibits human calpain I with an IC50 = 0.43 mu M. The potency of 1b compares very favorably with that of alpha-ketoester Cbz-Leu-Leu-CO2Et (IC50 = 0.60 mu M). Monomethyl ketophosphonate Cbz-Leu-Leu-P(O)(OH)(OCH3) (1a, IC50 = 5.2 mu M), an cl-ketoacid mimic, is less potent. Dibutyl and dibenzyl alpha-ketophosphonates 1c,e,f are much less potent calpain inhibitors than dimethyl alpha-ketophosphonate 1b. alpha-Ketophosphinate 1g (IC50 = 0.37 mu M) and alpha-ketophosphine oxide 1h (IC50 = 0.35 mu M) are also potent calpain inhibitors.

  DOI：

  10.1021/jm980325e

文献信息

• Stereoselective synthesis, solution structure and metal complexes of (1S,2S)-2-amino-1-hydroxyalkylphosphonic acids
  作者：Marcin Drag、Rafal Latajka、Elzbieta Gumienna-Kontecka、Henryk Kozlowski、Pawel Kafarski

  DOI：10.1016/s0957-4166(03)00278-7

  日期：2003.7

  The highly stereoselective synthesis of (1S,2S)-2-amino-1-hydroxyalkylphosphonic acids was achieved by addition of dimethyl phosphite to N-protected aminoaldehydes. Relative configuration and solution conformations of (1S,2S)-2-amino-lhydroxy-alkylphosphonic acids (in D2O) and their dimethyl esters (in CDCl3 and CD3OD) were established by means of NMR basing on the dependence between observed values of coupling constants ((3)J(HH), (3)J(PC), (3)J(HP)) and corresponding dihedral angles. Potentiometric and spectroscopic methods were used for the evaluation of the structure of the complexes of (1S,2S)-2-amino-lhydroxy-alkylphosphonic acids with Zn(II) and Cu(II) ions in aqueous solutions. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Novel Peptidyl Phosphorus Derivatives as Inhibitors of Human Calpain I
  作者：Ming Tao、Ron Bihovsky、Gregory J. Wells、John P. Mallamo

  DOI：10.1021/jm980325e

  日期：1998.9.1

  Dipeptidyl phosphorus compounds were synthesized as potential bioisosteric mimics of peptide alpha-ketoesters and alpha-ketoacids. alpha-Ketophosphonate Cbz-Leu-Leu-P(O)(OCH3)(2) (1b), containing an alpha-ketoester bioisostere, inhibits human calpain I with an IC50 = 0.43 mu M. The potency of 1b compares very favorably with that of alpha-ketoester Cbz-Leu-Leu-CO2Et (IC50 = 0.60 mu M). Monomethyl ketophosphonate Cbz-Leu-Leu-P(O)(OH)(OCH3) (1a, IC50 = 5.2 mu M), an cl-ketoacid mimic, is less potent. Dibutyl and dibenzyl alpha-ketophosphonates 1c,e,f are much less potent calpain inhibitors than dimethyl alpha-ketophosphonate 1b. alpha-Ketophosphinate 1g (IC50 = 0.37 mu M) and alpha-ketophosphine oxide 1h (IC50 = 0.35 mu M) are also potent calpain inhibitors.