(R)-(E)-β-(Fluoromethylene)-m-tyrosine | 160401-56-9

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: (R)-(E)-β-(Fluoromethylene)-m-tyrosine
• 英文别名: (E,2R)-2-amino-4-fluoro-3-(3-hydroxyphenyl)but-3-enoic acid
• CAS: 160401-56-9
• 化学式: C₁₀H₁₀FNO₃
• 分子量: 211.193
• InChiKey: LAUWCWCSEOWJMQ-WHXYTISESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -1.3
• 重原子数：
  15
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.1
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (R)-(E)-β-(Fluoromethylene)-m-tyrosine 在 乙酰基次氟酸酯 作用下， 以 溶剂黄146 、 三氟乙酸 为溶剂， 反应 0.42h， 生成 4-Fluoro-(E)-β-(fluoromethylene)-m-tyrosine 、 (R)-2-Fluoro-(E)-β-(fluoromethylene)-m-tyrosine 、 (R)-6-Fluoro-(E)-β-(fluoromethylene)-m-tyrosine 、 (R)-3-Acetoxy-2-amino-4,4-difluoro-3-(3-hydroxy-phenyl)-butyric acid
  参考文献：
  名称：

  Fluorination of (E)-.beta.-(Fluoromethylene)-m-Tyrosine: Regioselective Synthesis of 4-Fluoro-(E)-.beta.-(Fluoromethylene)-m-Tyrosine

  摘要：

  Fluorination of (R)- and (S)-(E)-beta-(fluoromethylene)-m-tyrosine (1) by acetyl hypofluorite yielded a mixture of the corresponding 2-fluoro- (2a), 6-fluaro- (2b), 4-fluoro- (2c), and 2,6-difluoro- (2d) derivatives along with a pair of diastereomeric products of addition across the vinylic double bond. A regioselective synthesis of 4-fluoro-(E)-beta-(fluoromethylene)-m-tyrosine has also been developed based on a fluorodestannylation reaction with elemental fluorine followed by acid hydrolysis. This reaction sequence yielded minor byproducts, namely, 4-fluoro-(Z)-beta-(fluoromethylene)-m-tyrosine (II), 4,6-difluoro- and 2,4-difluoro-(E)-beta-(fluoromethylene)-m-tyrosines (12a and 12b). All these products were completely separated by semipreparative HPLC and fully characterized by NMR and mass spectroscopy. Single crystal X-ray crystallographic analyses of 2-fluoro-, 4-fluoro-, and 6-fluoro-(E)-beta-(fluoromethylene)-m-tyrosines unequivocally established the structures of these amino acids.

  DOI：

  10.1021/jo00106a038
• 作为产物：
  描述：

  R-(E)-ethyl-2-trifluoroacetylamino-3-(3-methoxyphenyl)-4-fluoro-3-butenoate 在 氢溴酸 作用下， 反应 0.5h， 以90%的产率得到(R)-(E)-β-(Fluoromethylene)-m-tyrosine
  参考文献：
  名称：

  (E) and (Z)-β-fluoromethylene-m-tyrosines: Resolution and determination of configuration

  摘要：

  The geometrical isomers of beta-fluoromethylene-m-tyrosine (E and Z) were prepared and the R and S enantiomers of the biologically active (E)-isomer were separated with an enantiomeric excess >95% by the kinetic resolution of the racemic mixture using the enzyme alpha-chymotrypsin. The enantiomers of the (Z)-isomer were obtained by an acid catalyzed isomerization reaction. The absolute configurations of the isolated enantiomers were determined based on their CD spectral characteristics and chiral HPLC behavior. The R and S enantiomers of (E)-beta-fluoromethylene-m-tyrosine were also analyzed by single crystal X-ray crystallography.

  DOI：

  10.1016/0957-4166(95)00036-o

文献信息

• Fluorination of (E)-.beta.-(Fluoromethylene)-m-Tyrosine: Regioselective Synthesis of 4-Fluoro-(E)-.beta.-(Fluoromethylene)-m-Tyrosine
  作者：Goran Lacan、N. Satyamurthy、Jorge R. Barrio

  DOI：10.1021/jo00106a038

  日期：1995.1

  Fluorination of (R)- and (S)-(E)-beta-(fluoromethylene)-m-tyrosine (1) by acetyl hypofluorite yielded a mixture of the corresponding 2-fluoro- (2a), 6-fluaro- (2b), 4-fluoro- (2c), and 2,6-difluoro- (2d) derivatives along with a pair of diastereomeric products of addition across the vinylic double bond. A regioselective synthesis of 4-fluoro-(E)-beta-(fluoromethylene)-m-tyrosine has also been developed based on a fluorodestannylation reaction with elemental fluorine followed by acid hydrolysis. This reaction sequence yielded minor byproducts, namely, 4-fluoro-(Z)-beta-(fluoromethylene)-m-tyrosine (II), 4,6-difluoro- and 2,4-difluoro-(E)-beta-(fluoromethylene)-m-tyrosines (12a and 12b). All these products were completely separated by semipreparative HPLC and fully characterized by NMR and mass spectroscopy. Single crystal X-ray crystallographic analyses of 2-fluoro-, 4-fluoro-, and 6-fluoro-(E)-beta-(fluoromethylene)-m-tyrosines unequivocally established the structures of these amino acids.
• (E) and (Z)-β-fluoromethylene-m-tyrosines: Resolution and determination of configuration
  作者：Goran Laćan、N Satyamurthy、Jorge R Barrio

  DOI：10.1016/0957-4166(95)00036-o

  日期：1995.2

  The geometrical isomers of beta-fluoromethylene-m-tyrosine (E and Z) were prepared and the R and S enantiomers of the biologically active (E)-isomer were separated with an enantiomeric excess >95% by the kinetic resolution of the racemic mixture using the enzyme alpha-chymotrypsin. The enantiomers of the (Z)-isomer were obtained by an acid catalyzed isomerization reaction. The absolute configurations of the isolated enantiomers were determined based on their CD spectral characteristics and chiral HPLC behavior. The R and S enantiomers of (E)-beta-fluoromethylene-m-tyrosine were also analyzed by single crystal X-ray crystallography.