L-Phth-Leu-H | 64490-39-7

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异吲哚及其衍生物
• 英文名称: L-Phth-Leu-H
• 英文别名: N-phthalyl-L-leucinal；N-((S)-1-formyl-3-methyl-butyl)-phthalimide；N-((S)-1-Formyl-3-methyl-butyl)-phthalimid；(2S)-2-(1,3-dioxoisoindol-2-yl)-4-methylpentanal
• CAS: 64490-39-7
• 化学式: C₁₄H₁₅NO₃
• 分子量: 245.278
• InChiKey: IUHQSHUUXCBZPL-JTQLQIEISA-N

物化性质

• 沸点：
  360.9±25.0 °C(Predicted)
• 密度：
  1.214±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  54.4
• 氢给体数：
  0
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  L-Phth-Leu-H 在 盐酸 、 zinc(II) iodide 作用下， 以 1,4-二氧六环 、 二氯甲烷 为溶剂， 反应 61.5h， 生成 (2R,3S)-3-amino-2-hydroxy-5-methylhexanoic acid
  参考文献：
  名称：

  Renin inhibitors. Substitution of the leucyl residues of Leu-Leu-Val-Phe-OCH3 with 3-amino-2-hydroxy-5-methylhexanoic acid

  摘要：

  The 2S,3S and 2R,3S diastereoisomers of the hydroxy amino acid 3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA) were synthesized and substituted for the leucyl residues of Leu-Leu-Val-Phe-OCH3 to yield the following analogues: AHMHA-Leu-Val-Phe-OCH3, AHMHA-Val-Phe-OCH3, and Leu-AHMHA-Val-Phe-OCH3. These analogues were tested in vitro for their ability to inhibit human amniotic renin. All of the analogues were found to inhibit renin to some extent with inhibitory constants in the range of 10(-3) to 10(-4) M. The analogues AHMHA-Leu-Val-Phe-OCH3 and AHMHA-Val-Phe-OCH3 exhibited competitive inhibition when the 2S,3S isomer of AHMHA was employed and noncompetitive kinetics when the 2R,3S isomer of AHMHA was used. For the Leu-AHMHA-Val-Phe-OCH3 analogues, competitive kinetics were observed regardless of the isomer of AHMHA employed. These latter analogues also proved to be the most active in the above series.

  DOI：

  10.1021/jm00347a024
• 作为产物：
  描述：

  N-phthalimide-L-leucinyl chloride 在 Pd-BaSO₄ 氢气 作用下， 以 xylene 为溶剂， 反应 6.0h， 生成 L-Phth-Leu-H
  参考文献：
  名称：

  Renin inhibitors. Substitution of the leucyl residues of Leu-Leu-Val-Phe-OCH3 with 3-amino-2-hydroxy-5-methylhexanoic acid

  摘要：

  The 2S,3S and 2R,3S diastereoisomers of the hydroxy amino acid 3-amino-2-hydroxy-5-methylhexanoic acid (AHMHA) were synthesized and substituted for the leucyl residues of Leu-Leu-Val-Phe-OCH3 to yield the following analogues: AHMHA-Leu-Val-Phe-OCH3, AHMHA-Val-Phe-OCH3, and Leu-AHMHA-Val-Phe-OCH3. These analogues were tested in vitro for their ability to inhibit human amniotic renin. All of the analogues were found to inhibit renin to some extent with inhibitory constants in the range of 10(-3) to 10(-4) M. The analogues AHMHA-Leu-Val-Phe-OCH3 and AHMHA-Val-Phe-OCH3 exhibited competitive inhibition when the 2S,3S isomer of AHMHA was employed and noncompetitive kinetics when the 2R,3S isomer of AHMHA was used. For the Leu-AHMHA-Val-Phe-OCH3 analogues, competitive kinetics were observed regardless of the isomer of AHMHA employed. These latter analogues also proved to be the most active in the above series.

  DOI：

  10.1021/jm00347a024

文献信息

• Indium-Induced Addition of Bromomethylacrylates to Phthaloyl-Protected Amino Aldehydes
  作者：Steffen Steurer、Joachim Podlech

  DOI：10.1055/s-2002-28503

  日期：——

  The indium-mediated reaction of phthaloyl-protected α-amino aldehydes 1-4 with methyl 2-(bromomethyl)acrylate in aqueous solvents was investigated. The homoallyl alcohols 5-8 were formed in 72-89% yields, the anti-isomers being the major diastereoisomers (dr 45:55-18:82). Acid-catalyzed esterification (H2SO4 in Et2O) led to α-methylene γ-butyrolactones 9,10 with yields ranging from 88 to 99%. Conjugate addition of cyanide and thiophenolate led to the addition products with improved selectivities compared with additions to carbamate-protected substrates. During the conjugate addition of a cuprate, a trapping of the intermediate enolate by a phthaloyl carbonyl group occurred, leading to tetracycle 11 in 57% yield. The configuration of all diastereo­isomers could be established by three X-ray crystallographic analyses and by NMR spectroscopy.

  研究了在水溶剂中，邻苯二甲酰保护的α-氨基酸醛1-4与甲基2-（溴甲基）丙烯酸酯的铟介导反应。得到了同烯丙醇5-8，产率为72-89%，反式异构体为主要立体异构体（dr 45:55-18:82）。酸催化酯化（H2SO4在Et2O中）生成α-亚甲基γ-丁内酯9,10，产率范围为88至99%。氰化物和噻酚的共轭加成产物与加成到氨基甲酸酯保护的底物相比，选择性有所提高。在共轭加成铜试剂时，邻苯二甲酰羰基对中间体烯醇的捕获作用发生，导致了四环化合物11的生成，产率为57%。所有立体异构体的构型可以通过三次X射线晶体学分析和核磁共振波谱确定。
• Renin inhibitors containing 2-substituted statine
  申请人：Merck & Co., Inc.

  公开号：EP0157409A2

  公开（公告）日：1985-10-09

  Renin inhibitory peptides of the formula and analogs thereof inhibit renin and are useful for treating various forms of renin-associated hypertension and hyperaldosteronism.

  式中的肾素抑制肽及其类似物可抑制肾素，用于治疗各种形式的肾素相关性高血压和高醛固酮症。 及其类似物能抑制肾素，可用于治疗各种肾素相关性高血压和高醛固酮症。
• Di- and tri-peptidal renin inhibitors
  申请人：Merck & Co., Inc.

  公开号：EP0163237A2

  公开（公告）日：1985-12-04

  Renin inhibitory peptides of the formula and analogs thereof inhibit renin and are useful for treating various forms of renin-associated hypertension and hyperaldosteronism.

  式中的肾素抑制肽及其类似物可抑制肾素，用于治疗各种肾素相关性高血压和高醛固酮症。
• A synthesis of protected aminoalkyl epoxides from .alpha.-amino acids
  作者：Jay R. Luly、Joseph F. Dellaria、Jacob J. Plattner、Jeffrey L. Soderquist、Nwe Yi

  DOI：10.1021/jo00384a020

  日期：1987.4
• Optically Active Amino Aldehydes. II. Preparation of Cyclic Acetals of Quaternary Amino Aldehydes; Contribution to the Knowledge of the Stereospecificity of Muscarinic Activity¹
  作者：K. BALENOVIć、N. BREGANT、T. GALIJAN、Z. ŠTEFANAC、V. ŠKARIć

  DOI：10.1021/jo01107a026

  日期：1956.1