N-hydroxy-α-L-phenylalanine methylamide | 129155-87-9

• 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: N-hydroxy-α-L-phenylalanine methylamide
• 英文别名: (2S)-2-(hydroxyamino)-N-methyl-3-phenylpropanamide
• CAS: 129155-87-9
• 化学式: C₁₀H₁₄N₂O₂
• 分子量: 194.233
• InChiKey: UZCVQXYUBVJSKJ-VIFPVBQESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.32
• 重原子数：
  14.0
• 可旋转键数：
  4.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  61.36
• 氢给体数：
  3.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  甲酸 、 N-hydroxy-α-L-phenylalanine methylamide 在 乙酸酐 、 sodium hydroxide 作用下， 以 水 、 甲醇 为溶剂， 反应 0.5h， 以56%的产率得到(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
• 作为产物：
  描述：

  (2S)-2-氨基-3-苯丙酸乙酯 在 盐酸 、 盐酸羟胺 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 为溶剂， 反应 24.5h， 生成 N-hydroxy-α-L-phenylalanine methylamide
  参考文献：
  名称：

  旋光活性n-羟基-α-氨基酸酰胺的氧化制备

  摘要：

  提出了两种将光学活性α-氨基酸酰胺转化为标题化合物的途径。一种途径（途径A）的特征在于形成席夫碱6，其随后被氧化成相应的恶唑烷7。路线B的特征在于形成被羟基化为化合物12的咪唑啉11。在盐酸羟胺的存在下7和12的醇解得到标题化合物，总产率为65％至85％（途径A）和14％至21％（途径B）。

  DOI：

  10.1016/s0040-4020(01)81979-7

文献信息

• FEENSTRA, R. W.;STOKKINGREEF, E. H. M.;REICHWEIN, A. M.;LOUSBERG, W. B. H+, TETRAHEDRON, 46,(1990) N, C. 1745-1756
  作者：FEENSTRA, R. W.、STOKKINGREEF, E. H. M.、REICHWEIN, A. M.、LOUSBERG, W. B. H+

  DOI：——

  日期：——
• Oxidative preparation of optically active n-hydroxy-α-amino acid amides
  作者：R.W. FeenstraR̆、E.H.M. Stokkingreef、A.M. Reichwein、W.B.H. Lousberg、H.C.J. Ottenheijm、J. Kamphuis、W.H.J. Boesten、H.E. Schoemaker、E.M. Meijer

  DOI：10.1016/s0040-4020(01)81979-7

  日期：1990.1

  Two routes are presented for the conversion of optically active α-amino acid amides into the title compounds. One route(route A) features the formation of the Schiff's base 6 which is subsequently oxidized to the corresponding oxaziridines 7. Route B is characterized by the formation of an imidazolin 11 which is hydroxylated to compound 12. Alcoholysis of 7 and 12 in the presence of hydroxylamine hydrochloride

  提出了两种将光学活性α-氨基酸酰胺转化为标题化合物的途径。一种途径（途径A）的特征在于形成席夫碱6，其随后被氧化成相应的恶唑烷7。路线B的特征在于形成被羟基化为化合物12的咪唑啉11。在盐酸羟胺的存在下7和12的醇解得到标题化合物，总产率为65％至85％（途径A）和14％至21％（途径B）。
• 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.