Fmoc-D-4-氟苯丙氨酸 | 177966-64-2

• 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: Fmoc-D-4-氟苯丙氨酸
• 中文别名: 保护的-4-氟苯丙氨酸；FMOC-4-氟-D-苯丙氨酸；FMOC-D-4-氟苯丙氨酸；N-(9-芴甲氧羰酰基)-D-4-氟苯丙氨酸
• 英文名称: Fmoc-D-Phe(4-F)-OH
• 英文别名: (R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(4-fluorophenyl)propanoic acid；(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-(4-fluorophenyl)propanoic acid
• CAS: 177966-64-2
• 化学式: C₂₄H₂₀FNO₄
• mdl: MFCD00235900
• 分子量: 405.426
• InChiKey: IXUMACXMEZBPJG-JOCHJYFZSA-N

物化性质

• 熔点：
  180°C
• 比旋光度：
  35 º (c=1,DMF)
• 沸点：
  623.9±55.0 °C(Predicted)
• 密度：
  1.2642 (estimate)
• 稳定性/保质期：
  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  4.7
• 重原子数：
  30
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.166
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29242990
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H335
• 储存条件：
  存储于2-8°C阴凉干燥处

SDS

Name:	(R)-N-FMOC-4-Fluorophenylalanine 95% (98% E.E.) Material Safety Data Sheet
Synonym:	N-(9-Fluorenylmethoxycarbonyl)-4-Fluorophenyl-D-Alanine
CAS:	177966-64-2

Section 1 - Chemical Product MSDS Name:(R)-N-FMOC-4-Fluorophenylalanine 95% (98% E.E.) Material Safety Data Sheet
Synonym:N-(9-Fluorenylmethoxycarbonyl)-4-Fluorophenyl-D-Alanine

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
177966-64-2	(R)-N-FMOC-4-Fluorophenylalanine	95%	unlisted

Hazard Symbols: None Listed.
Risk Phrases: None Listed.

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Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
No information found.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Never give anything by mouth to an unconscious person. Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water. Wash mouth out with water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:
Treat symptomatically and supportively.

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use water spray, dry chemical, carbon dioxide, or chemical foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid breathing dust, vapor, mist, or gas. Avoid contact with eyes, skin, and clothing.
Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 177966-64-2: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
Follow the OSHA respirator regulations found in 29 CFR 1910.134 or European Standard EN 149. Use a NIOSH/MSHA or European Standard EN 149 approved respirator if exposure limits are exceeded or if irritation or other symptoms are experienced.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Solid
Color: white to off-white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: Not available.
Autoignition Temperature: Not available.
Flash Point: Not available.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C24H20FNO4
Molecular Weight: 405.42

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable under normal temperatures and pressures.
Conditions to Avoid:
Incompatible materials, dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, carbon dioxide, hydrogen fluoride gas.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 177966-64-2 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(R)-N-FMOC-4-Fluorophenylalanine - Not listed by ACGIH, IARC, or NTP.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Not regulated as a hazardous material.
IMO
Not regulated as a hazardous material.
RID/ADR
Not regulated as a hazardous material.

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: Not available.
Risk Phrases:
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
WGK (Water Danger/Protection)
CAS# 177966-64-2: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 177966-64-2 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 177966-64-2 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

Fmoc-D-Phe(4-F)-OH是一种苯丙氨酸衍生物。

反应信息

• 作为反应物：
  描述：

  Fmoc-D-4-氟苯丙氨酸 在 氯化亚砜 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 生成 (9H-fluoren-9-yl)methyl (R)-(1-chloro-3-(4-fluorophenyl)-1-oxopropan-2-yl)carbamate
  参考文献：
  名称：

  Discovery of a potent tubulin polymerization inhibitor: Synthesis and evaluation of water-soluble prodrugs of benzophenone analog

  摘要：

  Prodrugs have proven to be very useful in enhancing aqueous solubility of sparingly water-soluble drugs, thereby increasing in vivo efficacy without a need of special excipients. In vitro and in vivo evaluations of a number of amino acid prodrugs of 1, a previously identified potent tubulin polymerization inhibitor and cytotoxic against various cancer cell lines led to the discovery of 3 center dot HCl (L-valine attached) which is highly efficacious in mouse xenografts bearing human cancer. Pharmacokinetic analysis in rats revealed that compound 1 was released immediately upon administration of 3 center dot HCl intravenously, with rapid clearance of 3 center dot HCl indicating the effective cleavage of prodrug. Compound 3 center dot HCl (CKD-516) has now been progressed to phase 1 clinical trial. (C) 2010 Published by Elsevier Ltd.

  DOI：

  10.1016/j.bmcl.2010.05.060

文献信息

• [EN] REAGENT AND PROCESS FOR THE SITE-SPECIFIC DEOXYFLUORINATION OF PEPTIDES<br/>[FR] RÉACTIF ET PROCÉDÉ DE DÉSOXYFLUORATION DE PEPTIDES SPÉCIFIQUES AU SITE
  申请人：STUDIENGESELLSCHAFT KOHLE MBH

  公开号：WO2020007893A1

  公开（公告）日：2020-01-09

  The present invention refers to reagents and methods for preparing a peptide sequence having a [18F]fluoro-aromatic amino acid side which may be further substituted, in particular a 4-[18F]fluoro-phenylalanine side chain in peptide sequences, by chemoselective radio-deoxyfluorination of an aromatic amino acid residue, in particular a tyrosine residue using a traceless-activating group and the reagents used in said process.

  本发明涉及用于制备具有[18F]氟芳基氨基酸侧链的肽序列的试剂和方法，该侧链可以进一步取代，特别是在肽序列中的4-[18F]氟苯丙氨酸侧链，通过对芳香族氨基酸残基进行化学选择性的放射性脱氧氟化，特别是使用无痕激活基团和所述过程中使用的试剂对酪氨酸残基进行脱氧氟化。
• 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。
• A comprehensive study on the effect of backbone stereochemistry of a cyclic hexapeptide on membrane permeability and microsomal stability
  作者：Yuki Hosono、Jumpei Morimoto、Shinsuke Sando

  DOI：10.1039/d1ob02090k

  日期：——

  Backbone stereochemistry of cyclic peptides has been reported to have a great influence on microsomal stability and membrane permeability, two important factors that determine oral bioavailability. Here, we comprehensively investigated the correlation between the backbone stereochemistry of cyclic hexapeptide stereoisomers and their stability in liver microsomes, as well as passive membrane permeability

  据报道，环肽的骨架立体化学对微粒体稳定性和膜通透性有很大影响，而微粒体稳定性和膜通透性是决定口服生物利用度的两个重要因素。在这里，我们全面研究了环状六肽立体异构体的主链立体化学与其在肝微粒体中的稳定性以及被动膜通透性之间的相关性。
• Melanocortin Receptor-Specific Peptides
  申请人：AstraZeneca AB

  公开号：US20150252077A1

  公开（公告）日：2015-09-10

  The invention relates to melanocortin receptor-specific cyclic peptides of Formula (I) or a pharmaceutically acceptable salt thereof, where R 1 , R 2 , R 3 , R 4a , R 4b , R 4c , R 5 , x and y are as defined in the specification. These compounds are particularly useful in the treatments of energy homeostasis and metabolism related (e.g. diabetes), food intake related and/or energy balance and body weight related diseases, disorders and/or conditions, including obesity, overweight and diseases, disorders and/or conditions associated with obesity and/or overweight, such as type 2 diabetes and metabolic syndrome.

  本发明涉及公式（I）的黑素皮质素受体特异性环肽或其药学上可接受的盐，其中R1、R2、R3、R4a、R4b、R4c、R5、x和y如规范中所定义。这些化合物在能量稳态和代谢相关（例如糖尿病）、食物摄入相关和/或能量平衡和体重相关的疾病、疾病和/或状况，包括肥胖、超重以及与肥胖和/或超重相关的疾病、疾病和/或状况的治疗中特别有用，例如2型糖尿病和代谢综合征。
• Inhibition of Ras Signaling by Blocking Ras-Effector Interactions with Cyclic Peptides
  作者：Punit Upadhyaya、Ziqing Qian、Nicholas G. Selner、Sarah R. Clippinger、Zhengrong Wu、Roger Briesewitz、Dehua Pei

  DOI：10.1002/anie.201502763

  日期：2015.6.22

  cell‐penetrating properties. These cell‐permeable cyclic peptides inhibit Ras signaling by binding to Ras‐GTP and blocking its interaction with downstream proteins and they induce apoptosis of cancer cells. Our results demonstrate the feasibility of developing cyclic peptides for the inhibition of intracellular protein–protein interactions and of direct Ras inhibitors as a novel class of anticancer agents

  Ras基因在人类癌症中经常被激活，但是由于其表面上没有任何明显的结合口袋，因此通过传统的小分子方法，Ras突变蛋白在很大程度上仍然“不可吸收”。通过筛选组合肽库，然后进行结构-活性关系（SAR）分析，我们发现了同时具有Ras结合和细胞穿透特性的环状肽家族。这些可渗透细胞的环肽通过与Ras-GTP结合并阻断其与下游蛋白的相互作用来抑制Ras信号传导，并诱导癌细胞凋亡。我们的结果证明了开发环肽以抑制细胞内蛋白质间相互作用以及将直接Ras抑制剂作为一类新型抗癌剂的可行性。