(S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoic acid | 126312-57-0

• 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)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoic acid
• 英文别名: Boc-DMP-OH；Boc-2,6-Dimethyl-L-Phenylalanine；(2S)-3-(2,6-dimethylphenyl)-2-[(2-methylpropan-2-yl)oxycarbonylamino]propanoic acid
• CAS: 126312-57-0
• 化学式: C₁₆H₂₃NO₄
• 分子量: 293.363
• InChiKey: KJGYCJMJZYLARL-ZDUSSCGKSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  21
• 可旋转键数：
  6
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoic acid 在 盐酸 、 苯甲醚 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 1,4-二氧六环 、 N,N-二甲基甲酰胺 为溶剂， 反应 9.5h， 生成 2',6'-dimethyl-L-tyrosyl-L-prolyl-2',6'-dimethyl-L-phenylalanyl-L-phenylalanylamide
  参考文献：
  名称：

  Bifunctional [2‘,6‘-Dimethyl-l-tyrosine]endomorphin-2 Analogues Substituted at Position 3 with Alkylated Phenylalanine Derivatives Yield Potent Mixed μ-Agonist/δ-Antagonist and Dual μ-Agonist/δ-Agonist Opioid Ligands

  摘要：

  Endomorphin-2 (H-Tyr-Pro-Phe-Phe-NH2) and [Dmt(1)]EM-2 (Dmt = 2',6'-dimethyl-L-tyrosine) analogues, containing alkylated Phe(3) derivatives, 2'-monomethyl (2, 2'), 3',5'- and 2',6'-dimethyl (3, 3', and 4', respectively), 2',4',6'-trimethyl (6, 6'), 2'-ethyl-6'-methyl (7, 7'), and 2'-isopropyl-6'-methyl (8, 8') groups or Dmt (5, 5'), had the following characteristics: (i) [Xaa(3)]EM-2 analogues exhibited improved mu- and delta-opioid receptor affinities. The latter, however, were inconsequential (K-i(delta) = 491-3451 nM). (ii) [Dmt(1),Xaa(3)]EM-2 analogues enhanced mu- and delta-opioid receptor affinities (K-i(mu) = 0.069-0.32 nM; K-i(delta) = 1.83-99.8 nM) without kappa-opioid receptor interaction. (iii) There were elevated mu-bioactivity (IC50 = 0.12-14.4 nM) and abolished delta-agonism (IC50 > 10 mu M in 2', 3', 4', 5', 6'), although 4' and 6' demonstrated a potent mixed mu-agonism/delta-antagonism (for 4', IC50 mu = 0.12 and pA(2) = 8.15; for 6', IC50 mu = 0.21 nM and pA(2) = 9.05) and 7' was a dual mu-agonist/delta-agonist (IC50 mu = 0.17 nM; IC50 delta = 0.51 nM).

  DOI：

  10.1021/jm061238m
• 作为产物：
  描述：

  Boc-L-丝氨酸甲酯 在 2-双环己基膦-2',6'-二甲氧基联苯 、 咪唑 、 tris-(dibenzylideneacetone)dipalladium(0) 、 碘 、 三苯基膦 、 lithium hydroxide 、 锌 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 生成 (S)-2-((tert-butoxycarbonyl)amino)-3-(2,6-dimethylphenyl)propanoic acid
  参考文献：
  名称：

  Rapid Synthesis of Boc-2′,6′-dimethyl-l-tyrosine and Derivatives and Incorporation into Opioid Peptidomimetics

  摘要：

  The unnatural amino acid 2',6'-dimethyl-L-tyrosine has found widespread use in the development of synthetic opioid ligands. Opioids featuring this residue at the N-terminus often display superior potency at one or more of the opioid receptor types, but the availability of the compound is hampered by its cost and difficult synthesis. We report here a short, three-step synthesis of Boc-2',6'-dimethyl-L-tyrosine (3a) utilizing a microwave-assisted Negishi coupling for the key carbon-carbon bond forming step, and employ this chemistry for the expedient synthesis of other unnatural tyrosine derivatives. Three of these derivatives (3c, 3d, 30 have not previously been examined as Tyr(1) replacements in opioid ligands. We describe the incorporation of these tyrosine derivatives in a series of opioid peptidomimetics employing our previously reported tetrahydroquinoline (THQ) scaffold, and the binding and relative efficacy of each of the analogues at the three opioid receptor subtypes: mu (MOR), delta (DOR), and kappa (KOR).

  DOI：

  10.1021/acsmedchemlett.5b00344

文献信息

• [EN] PRODRUGS OF MITOCHODRIA-TARGETING OLIGOPEPTIDES<br/>[FR] PROMÉDICAMENTS D'OLIGOPEPTIDES CIBLANT LA MITOCHODRIE
  申请人：STEALTH BIOTHERAPEUTICS CORP

  公开号：WO2021262708A1

  公开（公告）日：2021-12-30

  Disclosed are various prodrugs of Elamipretide.

  Elamipretide的各种前药已被披露。
• Preparation of Constrained Unnatural Aromatic Amino Acids<i>via</i>Unsaturated Diketopiperazine Intermediate
  作者：Adriano Mollica、Roberto Costante、Sako Mirzaie、Simone Carradori、Giorgia Macedonio、Azzurra Stefanucci、Ettore Novellino

  DOI：10.1002/jhet.2489

  日期：2016.11

  Unnatural aromatic amino acids are useful tools in drug discovery, since their insertion in bioactive peptide sequences can change the side chains spatial orientation, the backbone conformation and above all, their bioactivity. In this communication, we propose a straightforward method to synthesize 2′,6′‐dimethyl‐tyrosine and 2′,6′‐dimehylphenyl‐alanine derivatives as handling building blocks for

  非天然芳族氨基酸是药物发现中的有用工具，因为它们插入生物活性肽序列中可以改变侧链的空间方向，主链构象以及最重要的是其生物活性。在本文中，我们提出了一种简单的方法来合成2'，6'-二甲基酪氨酸和2'，6'-二甲基苯基丙氨酸衍生物，作为通过不饱和二酮哌嗪（DKP）中间体进行肽合成的基础。
• [EN] MITOCHONDRIA-TARGETING PEPTIDES<br/>[FR] PEPTIDES CIBLANT LES MITOCHONDRIES
  申请人：STEALTH BIOTHERAPEUTICS CORP

  公开号：WO2019118878A1

  公开（公告）日：2019-06-20

  Disclosed are non-natural peptides useful for the treatment and prevention of ischemia-reperfusion injury (e.g., cardiac ischemia-reperfusion injury) or myocardial infarction.

  披露了用于治疗和预防缺血再灌注损伤（例如心脏缺血再灌注损伤）或心肌梗死的非天然肽。
• Synthesis of 2,6-Dimethyltyrosine-Like Amino Acids through Pinacolinamide-Enabled C–H Dimethylation of 4-Dibenzylamino Phenylalanine
  作者：Davide Illuminati、Anna Fantinati、Tiziano De Ventura、Daniela Perrone、Chiara Sturaro、Valentina Albanese、Erika Marzola、Virginia Cristofori、Julie Oble、Giovanni Poli、Claudio Trapella

  DOI：10.1021/acs.joc.1c02527

  日期：2022.3.4

  carrying methyl groups at positions 2 and 6 and diverse functionalities at position 4 has been achieved. The approach, which took advantage of a Pd-catalyzed directed C–H dimethylation of picolinamide derivatives, allowed the electronic and steric properties of the resulting amino acid derivatives to be altered by appending a variety of electron-withdrawing, electron-donating, or bulky groups.

  已经实现了在 2 位和 6 位带有甲基基团和在 4 位具有多种官能团的NH -Boc-或NH -Fmoc-保护的 L-苯丙氨酸的小型文库的合成。该方法利用 Pd 催化的甲基吡啶酰胺衍生物的定向 C-H 二甲基化，通过添加各种吸电子、给电子或庞大的物质，可以改变所得氨基酸衍生物的电子和空间特性。团体。
• Compositions and Methods for the Treatment of Amyotrophic Lateral Sclerosis, Parkinson's Disease, Parkinson's Disease with Dementia, Dementia with Lewy Bodies, and Multiple System Atrophy
  申请人：Keefe Dennis

  公开号：US20210023062A1

  公开（公告）日：2021-01-28

  The present disclosure provides novel methods for treating or preventing amyotrophic lateral sclerosis (ALS), methods for delaying the onset of neurological symptoms associated with ALS, increasing survival in subjects afflicted with ALS, and attenuating the decline of muscle strength associated with ALS in a subject in need thereof. The present disclosure also provides methods for treating or preventing α-synucleinopathy or TDP-43 proteinopathy. The methods comprise administering to the subject an effective amount of a mitochondria-targeting peptidomimetic compound, such as (R)-2-amino-N—((S)-1-(((S)-5-amino-1-(3-benzyl-1,2,4-oxadiazol-5-yl)pentyl)amino)-3-(4-hydroxy-2,6-dimethylphenyl)-1-oxopropan-2-yl)-5-guanidinopentanamide, or a pharmaceutically acceptable salt, stereoisomer, tautomer, hydrate, and/or solvate thereof.

  本公开提供了治疗或预防肌萎缩侧索硬化症（ALS）的新方法，延迟与ALS相关的神经症状的发作，增加患有ALS的受试者的生存率，并减轻需要的受试者与ALS相关的肌肉力量下降。本公开还提供了治疗或预防α-突触核蛋白病或TDP-43蛋白病的方法。这些方法包括向受试者施用有效量的以线粒体为靶点的肽类似化合物，例如（R）-2-氨基-N-（（S）-1-（（S）-5-氨基-1-（3-苄基-1,2,4-噁唑-5-基）戊基）氨基）-3-（4-羟基-2,6-二甲基苯基）-1-氧代丙酰-2-基）-5-鸟氨酰基戊酰胺，或其药学上可接受的盐、立体异构体、互变异构体、水合物和/或溶剂化物。