erythro-N-benzoyl-β-methyl-p-methoxy-phenylalanine methyl ester

• 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: erythro-N-benzoyl-β-methyl-p-methoxy-phenylalanine methyl ester
• 英文别名: methyl (2R,3R)-2-benzamido-3-(4-methoxyphenyl)butanoate
• 化学式: C₁₉H₂₁NO₄
• 分子量: 327.38
• InChiKey: UYQHGIGGTCSOBO-CXAGYDPISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  64.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  erythro-N-benzoyl-β-methyl-p-methoxy-phenylalanine methyl ester 在 三甲基铝 作用下， 以 四氢呋喃 、 正庚烷 、 二氯甲烷 为溶剂， 反应 24.0h， 生成
  参考文献：
  名称：

  藜芦生物碱 DEF 环立体三联体核心的从头合成。

  摘要：

  报道了藜芦生物碱 jervine (1)、环巴胺 (2) 和藜芦胺 (3) 东部立体三联体核心的合成。从已知的 β-甲基酪氨酸衍生物 (8) 开始，该路线利用非对映选择性底物控制的 1,2-还原来建立嵌入目标中的邻位氨基醇基序的立体化学。氧化脱芳构化被证明是合成在 jervine 和环巴胺中发现的螺环 DE 环连接的可行方法。

  DOI：

  10.1021/acs.joc.0c00685
• 作为产物：
  描述：

  2-phenyl-4-<α-E-p-methoxyphenylethylidene>-5(4H)-oxazolone 在 palladium on activated charcoal 氢气 、 sodium methylate 作用下， 以 甲醇 为溶剂， 25.0 ℃ 、344.74 kPa 条件下， 反应 6.0h， 生成 erythro-N-benzoyl-β-methyl-p-methoxy-phenylalanine methyl ester
  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

文献信息

• 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.
• <i>De Novo</i> Synthesis of the DEF-Ring Stereotriad Core of the <i>Veratrum</i> Alkaloids
  作者：Matthew A. Horwitz、Jacob G. Robins、Jeffrey S. Johnson

  DOI：10.1021/acs.joc.0c00685

  日期：2020.5.15

  The synthesis of the stereotriad core in the eastern portion of the Veratrum alkaloids jervine (1), cyclopamine (2), and veratramine (3) is reported. Starting from a known β-methyltyrosine derivative (8), the route utilizes a diastereoselective substrate-controlled 1,2-reduction to establish the stereochemistry of the vicinal amino alcohol motif embedded within the targets. Oxidative dearomatization

  报道了藜芦生物碱 jervine (1)、环巴胺 (2) 和藜芦胺 (3) 东部立体三联体核心的合成。从已知的 β-甲基酪氨酸衍生物 (8) 开始，该路线利用非对映选择性底物控制的 1,2-还原来建立嵌入目标中的邻位氨基醇基序的立体化学。氧化脱芳构化被证明是合成在 jervine 和环巴胺中发现的螺环 DE 环连接的可行方法。