(2S)-2-[formyl(hydroxy)amino]-N-methyl-3-phenylpropanamide

• 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: (2S)-2-[formyl(hydroxy)amino]-N-methyl-3-phenylpropanamide
• 化学式: C₁₁H₁₄N₂O₃
• 分子量: 222.244
• InChiKey: PJQHVJJJRIGTIF-JTQLQIEISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.6
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  69.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为产物：
  描述：

  L-苯基丙氨酸甲酰胺 在 盐酸羟胺 、 乙酸酐 、 sodium carbonate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 36.5h， 生成 (2S)-2-[formyl(hydroxy)amino]-N-methyl-3-phenylpropanamide
  参考文献：
  名称：

  Origin of the stereospecificity in binding hydroxamates of α- and β-phenylalanine methylamide to thermolysin revealed by the X-ray crystallographic study

  摘要：

  Optically active N-formyl-N-hydroxy-alpha-phenylalanine methylamide (1) and N-formyl-N-hydroxy-beta-phenylalanine methylamide (2) were evaluated as inhibitors for thermolysin (TLN) to find that while the D-form is more potent than its enantiomer in the case of the hydroxamate of alpha-Phe-NHMe, in the inhibition with hydroxamate of beta-Phe-NHMe, the L-isomer (K-i = 1.66 +/- 0.05 muM) is more effective than its enantiomer. In order to shed light on the stereochemical preference observed in the inhibitions, X-ray crystallographic analyses of the crystalline (TLND)-D-.-1 and (TLNL)-L-.-2 complexes were performed to the resolution of 2.1 Angstrom. While L-2 binds TLN like substrate does with its benzyl aromatic ring occupying the S-1' pocket, the electron density in the S-1' pocket in the complex of (TLND)-D-.-1 is weak and could best be accounted for by the methylcarbamoyl moiety. For both inhibitors, the hydroxamate moiety coordinates the active site zinc ion in a bidentate fashion. (C) 2003 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(03)00140-8

文献信息

• Origin of the stereospecificity in binding hydroxamates of α- and β-phenylalanine methylamide to thermolysin revealed by the X-ray crystallographic study
  作者：Seung-Jun Kim、Dong H Kim、Jung Dae Park、Joo-Rang Woo、Yonghao Jin、Seong Eon Ryu

  DOI：10.1016/s0968-0896(03)00140-8

  日期：2003.5

  Optically active N-formyl-N-hydroxy-alpha-phenylalanine methylamide (1) and N-formyl-N-hydroxy-beta-phenylalanine methylamide (2) were evaluated as inhibitors for thermolysin (TLN) to find that while the D-form is more potent than its enantiomer in the case of the hydroxamate of alpha-Phe-NHMe, in the inhibition with hydroxamate of beta-Phe-NHMe, the L-isomer (K-i = 1.66 +/- 0.05 muM) is more effective than its enantiomer. In order to shed light on the stereochemical preference observed in the inhibitions, X-ray crystallographic analyses of the crystalline (TLND)-D-.-1 and (TLNL)-L-.-2 complexes were performed to the resolution of 2.1 Angstrom. While L-2 binds TLN like substrate does with its benzyl aromatic ring occupying the S-1' pocket, the electron density in the S-1' pocket in the complex of (TLND)-D-.-1 is weak and could best be accounted for by the methylcarbamoyl moiety. For both inhibitors, the hydroxamate moiety coordinates the active site zinc ion in a bidentate fashion. (C) 2003 Elsevier Science Ltd. All rights reserved.