N-[(9H-芴-9-基甲氧基)羰基]-3-甲氧基-L-苯丙氨酸 | 206060-40-4

• 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-[(9H-芴-9-基甲氧基)羰基]-3-甲氧基-L-苯丙氨酸
• 中文别名: Fmoc-L-3-甲氧基苯丙氨酸；FMOC-3-甲氧基-L-苯丙氨酸
• 英文名称: (S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-3-(3-methoxyphenyl)propanoic acid
• 英文别名: (2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(3-methoxyphenyl)propanoic acid
• CAS: 206060-40-4
• 化学式: C₂₅H₂₃NO₅
• 分子量: 417.461
• InChiKey: IKKQVAWYVGALAQ-QHCPKHFHSA-N

物化性质

• 沸点：
  647.5±55.0 °C(Predicted)
• 密度：
  1.274±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  84.9
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Fmoc-l-3-methoxyphenylalanine
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-l-3-methoxyphenylalanine
CAS number: 206060-40-4

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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.
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: C25H23NO5
Molecular weight: 417.5

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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.

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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

反应信息

• 作为反应物：
  描述：

  N-[(9H-芴-9-基甲氧基)羰基]-3-甲氧基-L-苯丙氨酸 在 二乙胺 作用下， 以 二氯甲烷 、 环己烷 为溶剂， 反应 48.0h， 生成 (S)-2-Amino-3-(3-methoxy-phenyl)-propionic acid tert-butyl ester
  参考文献：
  名称：

  Toward a Rational Design of Peptide Inhibitors of Ribonucleotide Reductase:  Structure−Function and Modeling Studies

  摘要：

  Mammalian ribonucleotide reductase, a chemotherapeutic target, has two subunits, mR1 and mR2, and is inhibited by AcF(1)TLDADF(7), denoted P7. P7 corresponds to the C-terminus of mR2 and competes with mR2 for binding to mR1. We report results of a structure-function analysis of P7, obtained using a new assay measuring peptide ligand binding to mR1, that demonstrate stringent specificity for Phe at F-7, high specificity for Phe at F-1, and little specificity for the N-acyl group. They support a structural model in which the dominant interactions of P7 occur at two mR1 sites, the F-1 and F-7 subsites. The model is constructed from the structure of Escherichia colt R1 (eR1) complexed with the C-terminal peptide from eR2, aligned sequences of mR1 and eR1, and the trNOE-derived structure of mR1-bound P7. Comparison of this model with similar models constructed for mR1 complexed with other inhibitory ligands indicates that increased F-1 subsite interaction can offset lower F-7 subsite interaction and suggests strategies for the design of new, higher affinity inhibitors.

  DOI：

  10.1021/jm000335r
• 作为产物：
  描述：

  在 lithium hydroxide monohydrate 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 1.0h， 生成 N-[(9H-芴-9-基甲氧基)羰基]-3-甲氧基-L-苯丙氨酸
  参考文献：
  名称：

  使用简单实用的助剂对 α-氨基酸进行配体激活的 β-C-H 芳基化

  摘要：

  在过去十年中，人们广泛探索了使用助剂作为导向基团的 Pd 催化的羧酸衍生物的 β-CH 官能化。与不对称合成中使用最广泛的助剂相比，为 CH 活化开发的助剂的简单性和实用性仍有待提高。我们之前开发了一种简单的 N-甲氧基酰胺辅助剂来指导 β-CH 活化，尽管该系统与含有 α-氢原子的羧酸不兼容。在此，我们报道了一种吡啶型配体的开发，该配体克服了 N-甲氧基酰胺助剂的这种限制，从而显着改善了羧酸衍生物，尤其是 α-氨基酸的 β-芳基化。使用这种实用助剂的芳基化应用于非天然氨基酸的克级合成，

  DOI：

  10.1021/ja512690x

文献信息

• [EN] LIGAND-CONTROLLED C(SP3)-H ARYLATION AND OLEFINATION IN SYNTHESIS OF UNNATURAL CHIRAL ALPHA AMINO ACIDS<br/>[FR] ARYLATION COMMANDÉE PAR LIGAND DE C(SP3)-H ET OLÉFINATION UTILISABLES DANS LE CADRE DE LA SYNTHÈSE D'ACIDES ALPHA-AMINÉS CHIRAUX NON NATURELS
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2015131100A1

  公开（公告）日：2015-09-03

  The use of ligands to tune the reactivity and selectivity of transition metal-catalysts for C(-sp3)-H bond functionalization is a central challenge in synthetic organic chemistry. Herein, we report a rare example of catalyst-controlled C(sp3)-H arylation using pyridine and quinoline derivatives: the former promotes exclusive monoarylation, whereas the latter activates the catalyst further to achieve diarylation. Successive application of these ligands enables the sequential diarylation of a methyl group in an alanine derivative with two different aryl iodides, affording a wide range of β-Ar-p-Ar ' -cc-amino acids with excellent levels of diastereoselectivity (d.r. > 20:1). Both configurations of the β-chiral center can be accessed by choosing the order in which the aryl groups are installed. The use of a quinoline derivative as a ligand also enables C(sp3)-H olefination of a protected alanine.

  使用配体调节过渡金属催化剂对C(-sp3)-H键官能化的反应性和选择性是合成有机化学中的一个核心挑战。在这里，我们报告了一个罕见的催化剂控制的C(sp3)-H芳基化的例子，使用吡啶和喹啉衍生物：前者促进了独特的单芳基化，而后者进一步激活了催化剂以实现二芳基化。这些配体的连续应用使得在丙氨酸衍生物中的甲基基团上进行顺序二芳基化成为可能，使用两种不同的芳基碘化物，得到了一系列具有优异立体选择性的β-Ar-p-Ar' -cc-氨基酸（d.r. > 20:1）。通过选择芳基基团的安装顺序，可以访问β-手性中心的两种构型。使用喹啉衍生物作为配体还可以实现保护丙氨酸的C(sp3)-H烯烃化。
• 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。
• 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。
• Identification of Compounds Modifying A Cellular Response
  申请人：Thastrup Ole

  公开号：US20090239755A1

  公开（公告）日：2009-09-24

  The present invention relates to methods for identifying compounds capable of modulating a cellular response. The methods involve attaching living cells to solid supports comprising a library of test compounds. The test compounds are linked to the solid support via cleavable linkers and may thus be released from the solid supports. Solid supports comprising cells, wherein the cellular response of interest has been modulated are selected and the test compound of the solid support can then be identified. The cellular response may for example be changes in complex formation between proteins.

  本发明涉及识别能够调节细胞反应的化合物的方法。该方法涉及将活细胞附着在包含测试化合物库的固体支撑体上。测试化合物通过可切割的连接剂与固体支撑体连接，因此可以从固体支撑体释放出来。选择细胞被固体支撑体调节了感兴趣的细胞反应的固体支撑体，并且可以鉴定固体支撑体上的测试化合物。细胞反应可以是蛋白质复合物形成的变化，例如。
• Compounds Modifying Apoptosis
  申请人：Thastrup Ole

  公开号：US20080194537A1

  公开（公告）日：2008-08-14

  The present invention relates to compounds capable of inhibiting binding of the Smac protein to Inhibitors of apoptosis (IAPs). Such compounds are preferably capable of inhibiting IAP and thus may promote apoptosis or sensitize cells for apoptosis. The compounds may be used in the treatment of proliferative diseases, such as cancer.

  本发明涉及一种能够抑制Smac蛋白与凋亡抑制剂（IAPs）结合的化合物。这些化合物最好能够抑制IAP，从而可能促进细胞凋亡或增加细胞对凋亡的敏感性。这些化合物可用于治疗增生性疾病，如癌症。