(R)-N-FMOC-D-2-噻吩基丙氨酸 | 201532-42-5

• 物质功能分类: 生物化工 - 常见氨基酸及蛋白质类
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (R)-N-FMOC-D-2-噻吩基丙氨酸
• 中文别名: FMOC-D-3-噻吩基丙氨酸；FMOC-D-3-(2-噻吩)丙氨酸；(R)-2-[[[(9H-芴-9-基)甲氧基]羰基]氨基]-3-(噻吩-2-基)丙酸；FMOC-D-2-噻吩基丙氨酸；(R)-N-Fmoc-2-噻吩丙氨酸；(R)-芴甲氧羰基-D-2-噻吩基丙氨酸；Fmoc-D-Ala(2-Thienyl)-OH
• 英文名称: N-fluorenylmethoxycarbonyl-β-(2-thienyl)-D-alanine
• 英文别名: Fmoc-D-Thi-OH, Thi=β-(2-thienyl)alanine；Fmoc-D-Thi-OH；(R)-2-(((9H-fluoren-9-yl)methoxy)carbonylamino)-3-(thiophen-2-yl)propanoic acid；(R)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-3-(thiophen-2-yl)propanoic acid；(2R)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-3-thiophen-2-ylpropanoic acid
• CAS: 201532-42-5
• 化学式: C₂₂H₁₉NO₄S
• 分子量: 393.463
• InChiKey: PXBMQFMUHRNKTG-HXUWFJFHSA-N

物化性质

• 熔点：
  169 °C
• 沸点：
  623.4±55.0 °C(Predicted)
• 密度：
  1.343±0.06 g/cm3 (20 ºC 760 Torr)
• 稳定性/保质期：

  遵照规定使用和储存，则不会发生分解。

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  104
• 氢给体数：
  2
• 氢受体数：
  5

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• 安全说明：
  S24/25
• WGK Germany：
  3
• 海关编码：
  29309090
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335

SDS

Name:	(R)-N-FMOC-2-Thienylalanine 95% (98% E.E.) Material Safety Data Sheet
Synonym:	N-(9-Fluorenylmethoxycarbonyl)-2-Thienyl-D-Alanine
CAS:	201532-42-5

Section 1 - Chemical Product MSDS Name:(R)-N-FMOC-2-Thienylalanine 95% (98% E.E.) Material Safety Data Sheet
Synonym:N-(9-Fluorenylmethoxycarbonyl)-2-Thienyl-D-Alanine

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
201532-42-5	(R)-N-FMOC-2-Thienylalanine	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# 201532-42-5: 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: 169 deg C
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: C22H19NO4S
Molecular Weight: 393.46

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, dust generation.
Incompatibilities with Other Materials:
Oxidizing agents.
Hazardous Decomposition Products:
Nitrogen oxides, carbon monoxide, oxides of sulfur, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 201532-42-5 unlisted.
LD50/LC50:
Not available.
Carcinogenicity:
(R)-N-FMOC-2-Thienylalanine - 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# 201532-42-5: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 201532-42-5 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 201532-42-5 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

概述

(R)-N-FMOC-D-2-噻吩基丙氨酸又被称为N-芴甲氧羰基-β-(2-噻吩基)-D-丙氨酸，是一种非天然氨基酸。

制备方法

目前现有技术中，用于制备非天然氨基酸N-芴甲氧羰基-β-(2-噻吩基)-D-丙氨酸及其中间体的方法路线如下：首先将2-噻吩甲醇通过羟基氯酰化处理转化为2-氯甲基噻吩；然后与金属钠、乙醇以及乙酰氨基丙二酸二乙酯混合，生成相应的二乙酯；接着加入D-酰化酶进行拆分得到h-d-thi-oh；最后再与FMOC基团反应制得FMOC-D-2-噻吩基丙氨酸。尽管这种方法看起来操作步骤相对简单，但需要使用昂贵的D-酰化酶，导致成本较高，不适合商业化生产。

反应信息

• 作为反应物：
  描述：

  甲醇 、 苯乙酸 、 (R)-N-FMOC-D-2-噻吩基丙氨酸 在 N,N-二异丙基乙胺 、 哌啶 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.5h， 生成
  参考文献：
  名称：

  Lipophilic Permeability Efficiency Reconciles the Opposing Roles of Lipophilicity in Membrane Permeability and Aqueous Solubility

  摘要：

  As drug discovery moves increasingly toward previously "undruggable" targets such as protein-protein interactions, lead compounds are becoming larger and more lipophilic. Although increasing lipophilicity can improve membrane permeability, it can also incur serious liabilities, including poor water solubility, increased toxicity, and faster metabolic clearance. Here we introduce a new efficiency metric, especially relevant to "beyond rule of 5" molecules, that captures, in a simple, unitless value, these opposing effects of lipophilicity on molecular properties. Lipophilic permeability efficiency (LPE) is defined as log D-dec/w(7.4) - m(lipo)cLogP + b(scaffold), where log D-dec/w(7.4) is the experimental decadiene-water distribution coefficient (pH 7.4), cLogP is the calculated octanol-water partition coefficient, and m(lipo) and b(scaffold) are scaling factors to standardize LPE values across different cLogP metrics and scaffolds. Using a variety of peptidic and nonpeptidic macrocycle drugs, we show that LPE provides a functional assessment of the efficiency with which a compound achieves passive membrane permeability at a given lipophilicity.

  DOI：

  10.1021/acs.jmedchem.8b01259
• 作为产物：
  描述：

  diethyl 2-thienylmalonate 、 9-芴甲基-N-琥珀酰亚胺基碳酸酯 在 sodium hydroxide 、 盐酸 作用下， 以 丙酮 、 甲醇 、 水 为溶剂， 反应 60.0h， 以48g的产率得到(R)-N-FMOC-D-2-噻吩基丙氨酸
  参考文献：
  名称：

  一种非天然氨基酸N-芴甲氧羰基-β-(2-噻吩 基)-D-丙氨酸的制备方法

  摘要：

  本发明公开了一种非天然氨基酸N‑芴甲氧羰基‑β‑(2‑噻吩基)‑D‑丙氨酸的制备方法，主要解决原工艺中的复杂性，收率低，成本高等技术问题，本发明制备方法包括以下步骤：第一步，将2‑噻吩甲醇和氯酰化剂经过氯酰化制备成2‑氯甲基噻吩；第二步，将2‑氯甲基噻吩和乙酰氨基丙二酸二乙酯经过乙醇钠反应制得2‑噻吩基丙二酸二乙酯，第三步2‑噻吩基丙二酸二乙酯经过碱皂化、L‑乙酰化酶拆分并和fmoc‑基团反应，将所得L氨基保护产物过滤，将母液收集，加盐酸和甲醇溶液回流反应，经NMR检测反应进程，之后加入fmoc‑osu反应，TLC跟踪检测反应进程，之后经过在经过萃取杂质，酸化等，得到N‑芴甲氧羰基‑β‑(2‑噻吩基)‑D‑丙氨酸。

  公开号：

  CN106565665B

文献信息

• 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。
• Synthesis and Pharmacological Characterization of Novel Glucagon-like Peptide-2 (GLP-2) Analogues with Low Systemic Clearance
  作者：Kazimierz Wiśniewski、Javier Sueiras-Diaz、Guangcheng Jiang、Robert Galyean、Mark Lu、Dorain Thompson、Yung-Chih Wang、Glenn Croston、Alexander Posch、Diane M. Hargrove、Halina Wiśniewska、Régent Laporte、John J. Dwyer、Steve Qi、Karthik Srinivasan、Jennifer Hartwig、Nicky Ferdyan、Monica Mares、John Kraus、Sudarkodi Alagarsamy、Pierre J. M. Rivière、Claudio D. Schteingart

  DOI：10.1021/acs.jmedchem.5b01909

  日期：2016.4.14

  pharmacokinetic characteristics, a series of GLP-2 analogues containing Gly substitution at position 2, norleucine in position 10, and hydrophobic substitutions in positions 11 and/or 16 was designed and synthesized. In vitro receptor potency at the human GLP-2, selectivity vs the human GLP-1 and GCG receptors, and PK profile in rats were determined for the new analogues. A number of compounds more potent at the

  胰高血糖素样肽2受体激动剂具有治疗肠道疾病的潜力。天然的hGLP-2是一种33个氨基酸的胃肠道肽，由于其在人体内的半衰期非常短，因此不适合作为临床候选药物。为了寻找具有更好的药代动力学特性的GLP-2受体激动剂，设计并合成了一系列GLP-2类似物，其在2位，2位正亮氨酸，10位和11位和/或16位疏水取代含有甘氨酸取代。体外确定了新的类似物对人GLP-2的效价，对人GLP-1和GCG受体的选择性以及大鼠的PK谱。已发现许多在hGLP-2R上比天然激素更有效的化合物，表现出出色的受体选择性和非常低的全身清除率（CL）。类似物69（[Gly 2，Nle 10，d -Thi 11，Phe 16 ] hGLP-2-（1-30）-NH 2），72（[Gly 2，Nle 10，d -Phe 11，Leu 16 ] hGLP -2-（1-33）-OH），73（[Gly 2，Nle 10，d -Phe 11，Leu
• Structure-activity relationship study on artificial CXCR4 ligands possessing the cyclic pentapeptide scaffold: the exploration of amino acid residues of pentapeptides by substitutions of several aromatic amino acids
  作者：Tomohiro Tanaka、Wataru Nomura、Tetsuo Narumi、Ai Esaka、Shinya Oishi、Nami Ohashi、Kyoko Itotani、Barry J. Evans、Zi-xuan Wang、Stephen C. Peiper、Nobutaka Fujii、Hirokazu Tamamura

  DOI：10.1039/b908286g

  日期：——

  -Gly5-)]. In the present study, cyclic pentapeptide libraries that were designed by substitutions of several amino acids for D-Tyr1 and Arg2 in peptide 2 were prepared and screened to evaluate binding activity for CXCR4. The above structure-activity relationship study led to the finding of several potent CXCR4 ligands.

  以前，缩小14个残基的肽类CXCR4拮抗剂1导致开发出高效的CXCR4拮抗剂2 [环（-D -Tyr 1 -Arg 2 -Arg 3 -Nal 4 -Gly 5-）]。在本研究中，被设计由几个氨基酸的取代为环状五肽文库d -Tyr 1和Arg 2中的肽2的制备和筛选以评价CXCR4结合活性。上述结构-活性关系研究导致发现了几种有效的CXCR4配体。
• 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。