(S)-N,N-phthaloyl-o-formylphenylalanine | 185990-56-1

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (S)-N,N-phthaloyl-o-formylphenylalanine
• 英文别名: phth-ortho-formyl phenylalanine；N-Phth-2-formyl-L-Phe-OH；Ptht-2-formyl-L-Phe-OH；(S)-α-(1,3-Dihydro-1,3-dioxo-2H-isoindol-2-yl)-2-formylbenzenepropanoic acid；(2S)-2-(1,3-dioxoisoindol-2-yl)-3-(2-formylphenyl)propanoic acid
• CAS: 185990-56-1
• 化学式: C₁₈H₁₃NO₅
• 分子量: 323.305
• InChiKey: FSTMVGCXDMPDKD-HNNXBMFYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.9
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  91.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (S)-N,N-phthaloyl-o-formylphenylalanine 在 palladium on activated charcoal 吡啶 、 氢气 、 sodium cyanoborohydride 、 magnesium sulfate 、 一水合肼 、 N,N'-二环己基碳二亚胺 作用下， 以 1,4-二氧六环 、 乙醇 、 二氯甲烷 、 水 、 乙腈 为溶剂， 生成 C₁₉H₂₀N₂O₃
  参考文献：
  名称：

  Novel selective human melanocortin-3 receptor ligands: Use of the 4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one (Aba) scaffold

  摘要：

  In search of new selective antagonists and/or agonists for the human melanocortin receptor subtypes hMC1R to hMC5R to elucidate the specific biological roles of each GPCR, we modified the structures of the superagonist MT-II (Ac-Nle-c[Asp-HiS-D-Phe-Arg-Trp-Lys]-NH2) and the hMC3R/hMC4R antagonist SHU9119 (Ac-Nle-c[Asp-HiS-D-Nal(2 ')-Arg-Trp-Lys]-NH2) by replacing the HiS-D-Phe and HiS-D-Nal(2 ') fragments in MT-II and SHU9119, respectively, with Aba-Xxx (4-amino-1,2,4,5-tetrahydro-2-benzazepin-3-one-Xxx) dipeptidomimetics (Xxx = D-Phe/pCl-D-Phe/D-Nal(2 ')). Employment of the Aba mimetic yielded novel selective high affinity hMC3R and hMC3R/hMC5R antagonists. (C) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2007.02.020
• 作为产物：
  描述：

  2-氰基溴苄 在 镍 盐酸 、 cesium hydroxide 、 (2R,4R,5S)-1-(anthracen-9-ylmethyl)-5-ethenyl-2-[(S)-(prop-2-en-1-yloxy)(quinolin-4-yl)methyl]-1-azabicyclo[2.2.2]octan-1-ium bromide 、 水 、 氢气 、 sodium carbonate 、 柠檬酸 作用下， 以 四氢呋喃 、 吡啶 、 二氯甲烷 、 水 、 溶剂黄146 、 乙腈 为溶剂， -78.0~50.0 ℃ 、344.74 kPa 条件下， 反应 73.0h， 生成 (S)-N,N-phthaloyl-o-formylphenylalanine
  参考文献：
  名称：

  4-Amino-1,2,4,5-tetrahydro-2-benzazepin-3-ones及其螺环衍生物的β-转角性质的合成与评价

  摘要：

  制备了一系列 4-氨基-四氢-2-苯并氮杂-3-one 衍生物（Ac-Aba-Xxx-NHMe）作为四肽模拟物。考虑到与所谓的 Freidinger 内酰胺的结构相似性，通过 NMR 光谱（溶剂和温度依赖性）和分子建模研究了它们采用 β-转角构象的倾向。有趣的是，这些内酰胺中的大多数都采用扩展构象，只有螺-苯并氮杂酮 9 强烈偏好形成 β-转角。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

  DOI：

  10.1002/ejoc.200500996

文献信息

• T3P-Promoted, Mild, One-Pot Syntheses of Constrained Polycyclic Lactam Dipeptide Analogues via Stereoselective Pictet–Spengler and Meyers Lactamization Reactions
  作者：Mouhamad Jida、Olivier Van der Poorten、Karel Guillemyn、Zofia Urbanczyk-Lipkowska、Dirk Tourwé、Steven Ballet

  DOI：10.1021/acs.orglett.5b02145

  日期：2015.9.18

  diastereoselective synthesis of constrained 7,5- and 7,6-fused azabicycloalkanes. Using 2-formyl-L-tryptophan and 2-formyl-l-phenylalanine as bielectrophilic building blocks, T3P-mediated Pictet–Spengler and Meyers lactamization reactions were developed to present chiral and polycyclic aminoindolo- and aminobenzazepinone compounds in excellent yields. The conformationally constrained compounds can serve as

  描述了一种新的方便，温和的一锅法，用于受约束的7,5-和7,6-稠合的氮杂双环烷烃的非对映选择性合成。使用2-甲酰基-L-色氨酸和2-甲酰基-l-苯丙氨酸作为双亲电子构件，开发了T3P介导的Pictet-Spengler和Meyers内酰胺化反应，以优异的产率提供了手性和多环氨基吲哚-和氨基苯并ze庚酮化合物。构象受限的化合物可以用作拟肽研究或多杂环特权支架的模板。
• Efficient One-Pot Access to Trisubstituted 2-Benzazepin-3-ones as Constrained Pseudopeptide Analogues and Privileged Scaffolds
  作者：Olivier Van der Poorten、Mouhamad Jida、Dirk Tourwe、Steven Ballet

  DOI：10.2174/1573406413666171002122233

  日期：2018.5.11

  methodology is efficient since it only requires a limited number of synthetic steps in a final one-pot reaction. In most cases, the diastereomers could be separated by preparative RP-HPLC or via silica gel column chromatography. This is interesting from a medicinal chemistry point of view, since access is provided to the individual diastereomers. CONCLUSION We have developed an efficient and useful one-pot

  背景技术苯并ze庚因在药物化学领域受到极大关注，因为该支架已经被认为属于重要的特权模板家族。更具体地说，4-氨基-1,2,4,5-四氢-2-苯并ze庚因-3-酮（Aba）用作多种受约束的治疗性肽（转体）模拟物的核心结构。该模板的方法集中在环化上，环化形成了中心的7元氮杂a环。目的我们小组先前的研究允许通过在investigation庚酮环系统的4和5位上引入甲基取代基，以及1-芳基取代的化合物，来扩展4-氨基-苯并pin庚因-3-酮骨架中的取代模式。这些是迄今为止获得的仅有的三取代类似物。为了引入对肽模拟有用的多样化和构象约束的其他观点，可以在本论文中报道的Ugi反应中使用双功能底物。方法通过Ugi-3CR反应，从N-Phth保护的2-甲酰基-L-Phe-OH与一组胺和异氰化物衍生物开始，合成了1-甲酰胺基取代的Aba支架。应用最适合的反应条件，包括在室温下2小时内在无水Na2SO4存在下于MeOH（0
• χ-Space Screening of Dermorphin-Based Tetrapeptides through Use of Constrained Arylazepinone and Quinolinone Scaffolds
  作者：Olivier Van der Poorten、Robin Van Den Hauwe、Emilie Eiselt、Cecilia Betti、Karel Guillemyn、Nga N. Chung、François Hallé、Frédéric Bihel、Peter W. Schiller、Dirk Tourwé、Philippe Sarret、Louis Gendron、Steven Ballet

  DOI：10.1021/acsmedchemlett.7b00347

  日期：2017.11.9

  Herein, the synthesis of novel conformationally constrained amino acids, 4-amino-8-bromo-2-benzazepin-3-one (8-Br-Aba), 3-amino-3,4-dihydroquinolin-2-one, and regioisomeric 4-amino-naphthoazepinones (1- and 2-Ana), is described. Introduction of these constricted scaffolds into the N-terminal tetrapeptide of dermorphin (i.e., H-Tyr-d-Ala-Phe-Gly-NH2) induced significant shifts in binding affinity, selectivity

  本文中，合成了新的构象受限的氨基酸，4-氨基-8-溴-2-苯并enza庚因-3-一个（8-Br-Aba），3-氨基-3,4-二氢喹啉-2-一和区域异构体描述了4-氨基萘并pin庚酮（1-和2-Ana）。将这些收缩的支架引入dermorphin的N端四肽（即H-Tyr-d-Ala-Phe-Gly-NH2）会导致结合亲和力，选择性以及在μ-和δ-处的体外活性发生明显变化阿片受体（分别为MOP和DOP）。报道的受约束的μ-/δ-阿片样物质四肽铅H-Dmt-d-Arg-Aba-Gly-NH2通过应用各种受约束的结构单元进行修饰，以鉴于阿片样物质受体的活性确定最佳的空间方向。有趣的是，当芳香族部分转向肽序列的C端时，
• Variation of the Net Charge, Lipophilicity, and Side Chain Flexibility in Dmt¹-DALDA: Effect on Opioid Activity and Biodistribution
  作者：Alexandre Novoa、Sylvia Van Dorpe、Evelien Wynendaele、Mariana Spetea、Nathalie Bracke、Sofie Stalmans、Cecilia Betti、Nga N. Chung、Carole Lemieux、Johannes Zuegg、Matthew A. Cooper、Dirk Tourwé、Bart De Spiegeleer、Peter W. Schiller、Steven Ballet

  DOI：10.1021/jm3008079

  日期：2012.11.26

  The influence of the side chain charges of the second and fourth amino acid residues in the peptidic mu opioid lead agonist Dmt-D-Arg-Phe-Lys-NH2. ([Dmt(1)-DALDA) was examined. Additionally, to increase the overall lipophilicity of [Dmt(1)]-DALDA and to investigate the Phe(3) side chain flexibility, the final amide bond was N-methylated and Phe(3) was replaced by a constrained aminobenzazepine analogue. The in vitro receptor binding and activity of the peptides, as well as their in vivo transport (brain in- and efflux and tissue biodistribution) and antinociceptive properties after peripheral administration (ip and sc) in mice were determined. The structural modifications result in significant shifts of receptor binding, activity, and transport, properties. Strikingly, while [Dmt(1)]-DALDA and its N-methyl analogue, Dmt-D-Arg-Phe-NMeLys-NH2, showed a long-lasting antinociceptive effect (>7 h), the peptides with D-Cit(2) generate potent antinociception more rapidly (maximal effect at 1h postinjection) but also lose their analgesic activity faster when compared to [Dmt(1)]-DALDA. and [Dmit(1),NMeLys(4)]-DALDA.
• Azepinone-Containing Tetrapeptide Analogues of Melanotropin Lead to Selective <i>h</i>MC4R Agonists and <i>h</i>MC5R Antagonist
  作者：Olivier Van der Poorten、Krisztina Fehér、Koen Buysse、Debby Feytens、Ioanna Zoi、Steven D. Schwartz、José C. Martins、Dirk Tourwé、Minying Cai、Victor J. Hruby、Steven Ballet

  DOI：10.1021/ml500436s

  日期：2015.2.12

  To address the need for highly potent, metabolically stable, and selective agonists, antagonists, and inverse agonists at the melanocortin receptor subtypes, conformationally constrained indolo- and benzazepinone residues were inserted into the α-MSH pharmacophore, His(6)-Phe(7)-Arg(8)-Trp(9)-domain. Replacement of His(6) by an aminoindoloazepinone (Aia) or aminobenzazepinone (Aba) moiety led to hMC4R and hMC5R selective agonist and antagonist ligands, respectively (tetrapeptides 1 to 3 and 4, respectively). In peptides 1 to 3 and depending on the para-substituent of the d-Phe residue in position 2, the activity goes from allosteric partial agonism (1, R = H) to allosteric full agonism (2, R = F) and finally allosteric partial agonism (3, R = Br).