(2R,3S)-2-methyl-3-(N-phenylacetylamino)-4,4,4-trifluorobutyric acid | 159406-18-5

• 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: (2R,3S)-2-methyl-3-(N-phenylacetylamino)-4,4,4-trifluorobutyric acid
• CAS: 159406-18-5
• 化学式: C₁₃H₁₄F₃NO₃
• 分子量: 289.254
• InChiKey: PNRSZPFYZZOKKZ-KCJUWKMLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.0
• 重原子数：
  20.0
• 可旋转键数：
  5.0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  66.4
• 氢给体数：
  2.0
• 氢受体数：
  2.0

反应信息

• 作为反应物：
  描述：

  (2R,3S)-2-methyl-3-(N-phenylacetylamino)-4,4,4-trifluorobutyric acid 在 盐酸 作用下， 反应 11.0h， 生成 (2R,3S)-2-methyl-3-amino-4,4,4-trifluorobutyric acid
  参考文献：
  名称：

  Biomimetic Transamination of α-Alkyl β-Keto Carboxylic Esters. Chemoenzymatic Approach to the Stereochemically Defined α-Alkyl β-Fluoroalkyl β-Amino Acids

  摘要：

  Biomimetic transamination of the commercially available ethyl 2-methyl-3-keto-4,4,4-trifluorobutyrate (4) with benzylamine was shown to provide a simple access to the 2-methyl-3-amino-4,4,4-trifluorobutanoic acids, a hitherto unknown biologically relevant beta-amino acid. In sharp contrast to the alpha-unsubstituted beta-keto carboxylic esters the transamination of alpha-methyl beta-keto carboxylic ester 4 proceeds under mild reaction conditions, presumably, due to relative instability of the intermediate (Z)-enamine 6. Diastereoselectivity of the process was found to be controlled by the nature of the base-catalyst allowing for a stereodivergent preparation of (2R*,3S*)-8a and (2R*,3R*)-8b diastereomers as dominant reaction products. Preparation of all four diastereo- and enantiomerically pure optical isomers of the 2-methyl-3-amino-4,4,4-trifluorobutanoic acid was effectively accomplished by penicillin acylase-catalyzed resolution of the corresponding diastereomerically pure N-phenylacetyl derivatives. The whole process, a stereocontrolled chemoenzymatic approach, including the diastereoselective base-catalyzed [1,3]-proton shift reaction and the enantioselective penicillin acylase-catalyzed resolution, employs a simple set of reactions, inexpensive reagents, and mild reaction conditions, that would render it methodologically useful for preparing biologically interesting alpha,beta-disubstituted fluorinated beta-amino acids.

  DOI：

  10.1021/jo971777m
• 作为产物：
  描述：

  4,4,4-Trifluoro-2-methyl-3-{[1-phenyl-meth-(E)-ylidene]-amino}-butyric acid ethyl ester 在 盐酸 、 potassium hydrogencarbonate 作用下， 以 水 、 丙酮 为溶剂， 反应 10.0h， 生成 (2R,3S)-2-methyl-3-(N-phenylacetylamino)-4,4,4-trifluorobutyric acid
  参考文献：
  名称：

  Chemo-enzymatic approach to the synthesis of each of the four isomers of α-alkyl-β-fluoroalkyl-substituted β-amino acids

  摘要：

  Starting from easily available ethyl 2-methyl-4,4,4-trifluoroacetoacetate and benzylamine each of the four stereoisomers of alpha-methyl-beta-trifluoromethyl-beta-alanine have been synthesized in optically pure form via stereocontrolled chemo-enzymatic procedure including diastereoselective base-catalyzed [1,3]-proton shirt reaction and enantioselective penicillin acylase-catalyzed resolution.

  DOI：

  10.1016/0957-4166(94)80163-0