erythro-D-(2R,3R)-β-Methyltyrosine | 128573-10-4

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 苯丙酸
• 英文名称: erythro-D-(2R,3R)-β-Methyltyrosine
• 英文别名: erythro(2R,3R)-D-β-methyltyrosine；(2R,3R)-2-amino-3-(4-hydroxyphenyl)butanoic acid
• CAS: 128573-10-4
• 化学式: C₁₀H₁₃NO₃
• 分子量: 195.218
• InChiKey: CSKLNJOBXITXRM-HZGVNTEJSA-N

物化性质

• 沸点：
  370.6±32.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1.4
• 重原子数：
  14
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  83.6
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  erythro-D-(2R,3R)-β-Methyltyrosine 在 sodium hydroxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 生成 H-(2R,3S)-βMeTyr-Tic-Phe-Phe-NH2
  参考文献：
  名称：

  Side Chain Methyl Substitution in the δ-Opioid Receptor Antagonist TIPP Has an Important Effect on the Activity Profile

  摘要：

  The delta-opioid antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP-OH) or its C-terminal amide analogue was systematically modified topologically by substitution of each amino acid residue by all stereoisomers of the corresponding beta-methyl amino acid. The potency and selectivity (delta- vs mu- and kappa-opioid receptor) were evaluated by radioreceptor binding assays. Agonist or antagonist potency were assayed in the mouse vas deferens and in the guinea pig ileum. In the TIPP analogues containing L-beta-methyl amino acids the influence on delta-receptor affinity and on delta-antagonist potency is limited, the [(2S,3R)-beta-MePhe(3)]TIPP-OH analogue being among the most potent delta-antagonists reported. In the D-beta-methyl amino acid series, the [D-beta-MeTic(2)] analogues are delta-selective antagonists whereas [D-Tic(2)]TIPP-NH2 is a delta-agonist. NMR studies did not indicate any influence of the beta-methyl substituent on the conformation of the Tic residue. The [(2R,3S)-beta-MePhe(3)]TIPP-NH2 is a potent delta-agonist, its C-terminal carboxylic acid analogue being more delta-selective but displaying partial agonism in both the delta- and mu-bioassay. These results constitute further examples of a profound influence of beta-methyl substitution on the potency, selectivity, and signal transduction properties of a peptide.

  DOI：

  10.1021/jm981011u
• 作为产物：
  描述：

  (S)-(+)-4'-methoxy-3-phenylbutyric acid 在 palladium on activated charcoal lithium hydroxide 、 氢溴酸 、 双氧水 、 ammonium formate 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.5h， 生成 erythro-D-(2R,3R)-β-Methyltyrosine
  参考文献：
  名称：

  异常氨基酸的不对称合成：β-甲基酪氨酸的旋光异构体的合成

  摘要：

  β-甲基酪氨酸的光学纯异构体的合成已经完成。

  DOI：

  10.1016/s0040-4039(01)93367-2

文献信息

• An efficient procedure for the demethylation of aryl-methyl ethers in optically pure unusual amino acids
  作者：Guigm Li、Dinesh Patel、Victor J. Hruby

  DOI：10.1016/s0040-4039(00)73917-7

  日期：1993.1

  An efficient procedure was developed for the removal of methyl groups from aryl methyl ethers, without racemization, in derivatives of unusual amino acids that are of significant importance in the design of highly selective peptide protein ligands with specicific conformational topographical features. Demethylation of aromatic amino acids can result in an appreciable increase in receptor affinity,

  开发了一种有效的方法，用于在不消旋的情况下从芳基甲基醚中去除甲基，而该消旋体是不寻常氨基酸的衍生物，这对设计具有特定构象形貌特征的高选择性肽蛋白质配体具有重要意义。芳香族氨基酸的去甲基化可导致受体亲和力的显着增加，因此，已开发出的新的温和方法代表了Tyr（OMe）衍生物（包括新型侧链环或C-3修饰的类似物）去甲基化的简便实用方法。
• Efficient method for the total asymmetric synthesis of the isomers of .beta.-methyltyrosine
  作者：Ernesto Nicolas、K. C. Russell、J. Knollenberg、Victor J. Hruby

  DOI：10.1021/jo00078a042

  日期：1993.12

  Alpha-Amino acids modified at the beta-carbon atom can provide topographical constraints when incorporated into a peptide. Such modifications can modulate the physical, chemical, and biological properties of the compound. In order to properly evaluate the effect of such modifications, large-scale asymmetric syntheses of the isomers are needed. A method for the stereoselective large-scale synthesis of an four stereoisomers of beta-methyltyrosine is described in this paper. The stereochemistry of both the alpha- and beta-stereocenters was set using 4-phenyl-2-oxazolidinone as a chiral auxiliary. The key reactions were an asymmetric Michael-like addition of an organocuprate to a chiral alpha,beta-unsaturated acyloxazolidinone (beta center) and subsequent stereoselective electrophilic bromination of the resulting product (alpha center). Conversion of the bromide to the azide, catalyzed hydrolysis to the azido acid with simultaneous recovery of the chiral auxiliary, reduction of the azide, and final deprotection of the phenol group afforded the desired amino acids. In general, the reactions were performed in yields over 80 %, and the isomers were obtained in enantiomeric purities of 98:2 to 99:1.
• NICOLAS, ERNESTO;DHARANIPRAGADA, RAMALINGA;TOTH, GEZA;HRURBY, VICTOR J., TETRAHEDRON LETT., 30,(1989) N9, C. 6845-6848
  作者：NICOLAS, ERNESTO、DHARANIPRAGADA, RAMALINGA、TOTH, GEZA、HRURBY, VICTOR J.

  DOI：——

  日期：——
• Side Chain Methyl Substitution in the δ-Opioid Receptor Antagonist TIPP Has an Important Effect on the Activity Profile
  作者：Dirk Tourwé、Els Mannekens、Trang Nguyen Thi Diem、Patricia Verheyden、Hendrika Jaspers、Géza Tóth、Antal Péter、István Kertész、Gabriella Török、Nga N. Chung、Peter W. Schiller

  DOI：10.1021/jm981011u

  日期：1998.12.1

  The delta-opioid antagonist H-Tyr-Tic-Phe-Phe-OH (TIPP-OH) or its C-terminal amide analogue was systematically modified topologically by substitution of each amino acid residue by all stereoisomers of the corresponding beta-methyl amino acid. The potency and selectivity (delta- vs mu- and kappa-opioid receptor) were evaluated by radioreceptor binding assays. Agonist or antagonist potency were assayed in the mouse vas deferens and in the guinea pig ileum. In the TIPP analogues containing L-beta-methyl amino acids the influence on delta-receptor affinity and on delta-antagonist potency is limited, the [(2S,3R)-beta-MePhe(3)]TIPP-OH analogue being among the most potent delta-antagonists reported. In the D-beta-methyl amino acid series, the [D-beta-MeTic(2)] analogues are delta-selective antagonists whereas [D-Tic(2)]TIPP-NH2 is a delta-agonist. NMR studies did not indicate any influence of the beta-methyl substituent on the conformation of the Tic residue. The [(2R,3S)-beta-MePhe(3)]TIPP-NH2 is a potent delta-agonist, its C-terminal carboxylic acid analogue being more delta-selective but displaying partial agonism in both the delta- and mu-bioassay. These results constitute further examples of a profound influence of beta-methyl substitution on the potency, selectivity, and signal transduction properties of a peptide.
• Asymmetric synthesis of unusual amino acids: Synthesis of optically pure isomers of β-methyltyrosine
  作者：Ernesto Nicolas、Ramalinga Dharanipragada、Geza Toth、Victor J Hruby

  DOI：10.1016/s0040-4039(01)93367-2

  日期：1989.1

  Synthesis of optically pure isomers of β-methyltyrosine has been accomplished.

  β-甲基酪氨酸的光学纯异构体的合成已经完成。