N-芴甲氧羰基-L-3-氯苯丙氨酸 | 198560-44-0

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 苯丙氨酸类衍生物
• 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
• 中文名称: N-芴甲氧羰基-L-3-氯苯丙氨酸
• 英文名称: Fmoc-Phe(3-Cl)-OH
• 英文别名: Fmoc-L-3-Chlorophenylalanine；(2S)-3-(3-chlorophenyl)-2-(9H-fluoren-9-ylmethoxycarbonylamino)propanoic acid
• CAS: 198560-44-0
• 化学式: C₂₄H₂₀ClNO₄
• 分子量: 421.88
• InChiKey: UOZAKKJRIKXQPY-QFIPXVFZSA-N

物化性质

• 沸点：
  640.9±55.0 °C(Predicted)
• 密度：
  1.337±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储温度应保持在0°C。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-3-chloro-l-phenylalanine
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

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Section 3. Composition/information on ingredients.
Ingredient name: Fmoc-3-chloro-l-phenylalanine
CAS number: 198560-44-0

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Section 4. First aid measures
Skin contact: Immediately wash skin with copious amounts of water for at least 15 minutes while removing
contaminated clothing and shoes. If irritation persists, seek medical attention.
Eye contact: Immediately wash skin with copious amounts of water for at least 15 minutes. Assure adequate
flushing of the eyes by separating the eyelids with fingers. If irritation persists, seek medical
attention.
Inhalation: Remove to fresh air. In severe cases or if symptoms persist, seek medical attention.
Ingestion: Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.

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Section 5. Fire fighting measures
In the event of a fire involving this material, alone or in combination with other materials, use dry
powder or carbon dioxide extinguishers. Protective clothing and self-contained breathing apparatus
should be worn.

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Section 6. Accidental release measures
Personal precautions: Wear suitable personal protective equipment which performs satisfactorily and meets local/state/national
standards.
Respiratory precaution: Wear approved mask/respirator
Hand precaution: Wear suitable gloves/gauntlets
Skin protection: Wear suitable protective clothing
Eye protection: Wear suitable eye protection
Methods for cleaning up: Mix with sand or similar inert absorbent material, sweep up and keep in a tightly closed container
for disposal. See section 12.
Environmental precautions: Do not allow material to enter drains or water courses.

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Section 7. Handling and storage
Handling: This product should be handled only by, or under the close supervision of, those properly qualified
in the handling and use of potentially hazardous chemicals, who should take into account the fire,
health and chemical hazard data given on this sheet.
Store in closed vessels, refrigerated.
Storage:

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Section 8. Exposure Controls / Personal protection
Engineering Controls: Use only in a chemical fume hood.
Personal protective equipment: Wear laboratory clothing, chemical-resistant gloves and safety goggles.
General hydiene measures: Wash thoroughly after handling. Wash contaminated clothing before reuse.

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Section 9. Physical and chemical properties
Appearance: Not specified
Boiling point: No data
No data
Melting point:
Flash point: No data
Density: No data
Molecular formula: C24H20ClNO4
Molecular weight: 421.9

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Section 10. Stability and reactivity
Conditions to avoid: Heat, flames and sparks.
Materials to avoid: Oxidizing agents.
Possible hazardous combustion products: Carbon monoxide, nitrogen oxides, hydrogen chloride.

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Section 11. Toxicological information
No data.

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Section 12. Ecological information
No data.

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Section 13. Disposal consideration
Arrange disposal as special waste, by licensed disposal company, in consultation with local waste
disposal authority, in accordance with national and regional regulations.

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Section 14. Transportation information
Non-harzardous for air and ground transportation.

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Section 15. Regulatory information
No chemicals in this material are subject to the reporting requirements of SARA Title III, Section
302, or have known CAS numbers that exceed the threshold reporting levels established by SARA
Title III, Section 313.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

Fmoc-3-氯-L-苯丙氨酸是一种苯丙氨酸衍生物。

反应信息

• 作为反应物：
  描述：

  N-芴甲氧羰基-L-3-氯苯丙氨酸 在 哌啶 、 1-羟基苯并三唑 、 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 、 N,N-二异丙基乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 28.5h， 生成 4-((S)-2-amino-3-(((S)-3-(3-chlorophenyl)-1-(methylamino)-1-oxopropan-2-yl)amino)-3-oxopropyl)benzamide
  参考文献：
  名称：

  金鸡纳生物碱季铵盐作为不对称相转移催化剂催化手性苯丙氨酸衍生物两种对映体的合成。

  摘要：

  描述了使用两种假对映体相转移催化剂来实际合成非天然苯丙氨酸衍生物的两种对映体。在O-烯丙基-N-(9-蒽甲基)辛可宁溴化物(1f)和O-烯丙基-N-(9-)催化下，甘氨酸席夫碱与取代的苄基溴和1-(溴甲基)萘发生不对称α-烷基化反应分别以优异的产率和对映选择性获得了一系列非天然α-氨基酸衍生物的(R)-和(S)-对映体。该合成方法简单、可规模化，产物的立体化学完全可预测和控制：辛可宁型相转移催化剂1f得到(R)-α-氨基酸衍生物，辛可尼定型相转移催化剂1i得到(R)-α-氨基酸衍生物。 (S)-α-氨基酸衍生物。

  DOI：

  10.3390/molecules23061421
• 作为产物：
  描述：

  氯甲酸-9-芴基甲酯 、 (S)-3-chlorophenylalanine hydrochloride 在 sodium carbonate 作用下， 以 1,4-二氧六环 、 水 为溶剂， 反应 22.0h， 以59%的产率得到N-芴甲氧羰基-L-3-氯苯丙氨酸
  参考文献：
  名称：

  金鸡纳生物碱季铵盐作为不对称相转移催化剂催化手性苯丙氨酸衍生物两种对映体的合成。

  摘要：

  描述了使用两种假对映体相转移催化剂来实际合成非天然苯丙氨酸衍生物的两种对映体。在O-烯丙基-N-(9-蒽甲基)辛可宁溴化物(1f)和O-烯丙基-N-(9-)催化下，甘氨酸席夫碱与取代的苄基溴和1-(溴甲基)萘发生不对称α-烷基化反应分别以优异的产率和对映选择性获得了一系列非天然α-氨基酸衍生物的(R)-和(S)-对映体。该合成方法简单、可规模化，产物的立体化学完全可预测和控制：辛可宁型相转移催化剂1f得到(R)-α-氨基酸衍生物，辛可尼定型相转移催化剂1i得到(R)-α-氨基酸衍生物。 (S)-α-氨基酸衍生物。

  DOI：

  10.3390/molecules23061421

文献信息

• Selective Substrates and Activity-Based Probes for Imaging of the Human Constitutive 20S Proteasome in Cells and Blood Samples
  作者：Wioletta Rut、Marcin Poręba、Paulina Kasperkiewicz、Scott J. Snipas、Marcin Drąg

  DOI：10.1021/acs.jmedchem.8b00026

  日期：2018.6.28

  the HyCoSuL approach, we designed and synthesized novel and selective fluorogenic substrates for each of these three constitutive 20S proteasome activities and applied them to assess inhibition of proteasome subunits by MG-132 and a clinically used inhibitor bortezomib. Our results confirm the utility of designed substrates in biochemical assays. Furthermore, selective peptide sequences obtained in this

  蛋白酶体是维持蛋白质稳态的关键酶复合物。蛋白酶体功能紊乱导致包括癌症，自身免疫和神经退行性疾病在内的病理。因此，蛋白酶体构成药物开发的极好的分子靶标。在这里，我们使用HyCoSuL方法为这三个20S组成型蛋白酶体活性中的每一个设计和合成了新颖的选择性荧光底物，并将它们应用于评估MG-132和临床使用的硼替佐米对蛋白酶体亚基的抑制作用。我们的结果证实了设计的底物在生化分析中的实用性。此外，以此方式获得的选择性肽序列用于构建荧光团标记的基于活性的探针，然后用于同时检测HEK-293F细胞和红细胞裂解液中的每个20S组成型蛋白酶体亚基。总体而言，我们描述了一种简单而快速的方法，可用于测量全血样本中20S组成型蛋白酶体的活性，该方法可以早期诊断与异常上调的蛋白酶体活性有关的病理状态。
• Optimization of linear and cyclic peptide inhibitors of KEAP1-NRF2 protein-protein interaction
  作者：Stefania Colarusso、Daniele De Simone、Tommaso Frattarelli、Matteo Andreini、Mauro Cerretani、Antonino Missineo、Daniele Moretti、Sara Tambone、Georg Kempf、Martin Augustin、Stefan Steinbacher、Ignacio Munoz-Sanjuan、Larry Park、Vincenzo Summa、Licia Tomei、Alberto Bresciani、Celia Dominguez、Leticia Toledo-Sherman、Elisabetta Bianchi

  DOI：10.1016/j.bmc.2020.115738

  日期：2020.11

  Inhibition of KEAP1-NRF2 protein-protein interaction is considered a promising strategy to selectively and effectively activate NRF2, a transcription factor which is involved in several pathologies such as Huntington’s disease (HD). A library of linear peptides based on the NRF2-binding motifs was generated on the nonapeptide lead Ac-LDEETGEFL-NH2 spanning residues 76–84 of the Neh2 domain of NRF2

  抑制KEAP1-NRF2蛋白质-蛋白质相互作用被认为是有选择地和有效地激活NRF2的一种有前途的策略，NRF2是一种转录因子，涉及多种病理学，例如亨廷顿舞蹈病（HD）。在非肽铅Ac-LDEETGEFL-NH 2上生成了基于NRF2结合基序的线性肽库跨越NRF2 Neh2域的76-84位残基，目的是用非酸性氨基酸取代E78，E79和E82。基于结构的设计还旨在更深入地了解T80副口袋的功能和可及性。研究了使用不同种类的环肽以及与细胞穿透肽结合的提高细胞通透性的方法。这一见识将指导大环化合物，肽模拟物以及最重要的是中性小脑穿透分子的未来设计，以评估NRF2激活剂是否可用于HD。
• Orthogonally Protected Thiazole and Isoxazole Diamino Acids: An Efficient Synthetic Route
  作者：Jeffrey D. Butler、Keith C. Coffman、Kristin T. Ziebart、Michael D. Toney、Mark J. Kurth

  DOI：10.1002/chem.201001492

  日期：——

  An efficient strategy has been developed for the synthesis of heteroaromatic amino acids (HAAs). These methods generate mono‐ or orthogonally protected diamino acids from β‐amino acids (see scheme). Their synthetic reliability and biological potential was demonstrated through the synthesis of an anthranilate synthase (AS) and isochorismate synthase (IS) inhibitor with improved potency.

  已开发出一种用于合成杂芳族氨基酸 (HAA)的有效策略。这些方法从 β-氨基酸生成单或正交保护的二氨基酸（见方案）。通过合成具有改进效力的邻氨基苯甲酸合酶 (AS) 和异分支酸合酶 (IS) 抑制剂，证明了它们的合成可靠性和生物学潜力。
• The Meta-Position of Phe4 in Leu-Enkephalin Regulates Potency, Selectivity, Functional Activity, and Signaling Bias at the Delta and Mu Opioid Receptors
  作者：Robert J. Cassell、Krishna K. Sharma、Hongyu Su、Benjamin R. Cummins、Haoyue Cui、Kendall L. Mores、Arryn T. Blaine、Ryan A. Altman、Richard M. van Rijn

  DOI：10.3390/molecules24244542

  日期：——

  As tool compounds to study cardiac ischemia, the endogenous δ-opioid receptors (δOR) agonist Leu5-enkephalin and the more metabolically stable synthetic peptide (d-Ala2, d-Leu5)-enkephalin are frequently employed. However, both peptides have similar pharmacological profiles that restrict detailed investigation of the cellular mechanism of the δOR’s protective role during ischemic events. Thus, a need remains for δOR peptides with improved selectivity and unique signaling properties for investigating the specific roles for δOR signaling in cardiac ischemia. To this end, we explored substitution at the Phe4 position of Leu5-enkephalin for its ability to modulate receptor function and selectivity. Peptides were assessed for their affinity to bind to δORs and µ-opioid receptors (µORs) and potency to inhibit cAMP signaling and to recruit β-arrestin 2. Additionally, peptide stability was measured in rat plasma. Substitution of the meta-position of Phe4 of Leu5-enkephalin provided high-affinity ligands with varying levels of selectivity and bias at both the δOR and µOR and improved peptide stability, while substitution with picoline derivatives produced lower-affinity ligands with G protein biases at both receptors. Overall, these favorable substitutions at the meta-position of Phe4 may be combined with other modifications to Leu5-enkephalin to deliver improved agonists with finely tuned potency, selectivity, bias and drug-like properties.

  作为研究心脏缺血的工具化合物，内源性δ-阿片受体（δOR）激动剂Leu5-恩啡啶和更具代谢稳定性的合成肽（d-Ala2，d-Leu5）-恩啡啶经常被使用。然而，这两种肽具有类似的药理特性，限制了对δOR在缺血事件中保护作用的细胞机制进行详细研究。因此，需要具有改进选择性和独特信号特性的δOR肽，以便研究心脏缺血中δOR信号的特定作用。为此，我们探索了Leu5-恩啡啶的Phe4位置的取代物对调节受体功能和选择性的能力。评估了肽对δOR和µ-阿片受体（µOR）的结合亲和力以及抑制cAMP信号和招募β-阻滞蛋白2的效力。此外，还测量了肽在大鼠血浆中的稳定性。通过在Leu5-恩啡啶的Phe4的间位进行取代，提供了具有不同选择性和偏向性水平的高亲和力配体，同时改善了肽的稳定性，而用吡啶衍生物进行取代则产生了在两种受体上具有G蛋白偏向性的亲和力较低的配体。总的来说，Phe4的间位的这些有利取代物可以与Leu5-恩啡啶的其他修饰结合，提供具有精心调节的效力、选择性、偏向性和药物样性质的改进激动剂。
• Synthesis and biological activity of FGLamide allatostatin analogs with Phe³residue modifications
  作者：Yong Xie、Meizi Wang、Li Zhang、Xiaoqing Wu、Xinling Yang、Stephen S. Tobe

  DOI：10.1002/psc.2906

  日期：2016.9

  allatostatin neuropeptide mimic (H17) is a potential insect growth regulator which inhibits the production of juvenile hormone by the corpora allata. To find more evidence to reveal the structure–activity relationships of the Phe3 residue in the C‐terminal conserved pentapeptide and search for novel analogs with high activity, a series of Phe3 residue‐modified analogs were designed and synthesized using H17 as

  FGLamide allatostatin神经肽模拟物（H17）是一种潜在的昆虫生长调节剂，可抑制allcorp幼体产生幼体激素。为了找到更多证据揭示在C端保守的五肽中Phe 3残基的结构-活性关系，并寻找具有高活性的新类似物，以H17为先导设计并合成了一系列Phe 3残基修饰的类似物。化合物。生物测定使用保幼激素（JH）生产由语料库allata蟑螂的Diploptera点状显示，类似物4，11，和13在体外显示出强大的抑制JH产生的能力，IC 50分别为38.5、22.5和26 nM。同样，类似物2（IC 50：89.5 nM）的活性被证明与H17的活性大致相当。基于Phe 3残基的一级结构-活性关系，我们建议对于含有六元芳环的类似物，去除Phe 3的亚甲基或邻卤素或p卤素取代的苯环可以提高抑制JH生物合成的能力。这项研究对于设计用于昆虫管理的新阿托伐他汀类似物将是有用的。版权所有©2016欧洲多肽协会和John