Fmoc-L-天冬氨酸 4-烯丙酯 | 146982-24-3

• 物质功能分类: 生物化工 - 生化试剂 - 氨基酸
• 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-L-天冬氨酸 4-烯丙酯
• 中文别名: N-芴甲氧羰基-L-天冬氨酸4-烯丙酯；N-[(2-丙烯-1-基氧基)羰基]-L-天冬氨酸4-(9H-芴-9-基甲基)酯；Fmoc-L-天冬氨酸4-烯丙酯；N-芴甲氧羰基-L-天冬氨酸 4-烯丙酯；Fmoc-Asp(OAll)-OH
• 英文名称: N-alpha-(9-fluorenylmethyloxycarbonyl)-L-aspartic acid beta-allyl ester
• 英文别名: Fmoc-Asp(OAllyl)-OH；Fmoc-Asp-OAll；Fmoc-Asp(OAll)-OH；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-4-oxo-4-prop-2-enoxybutanoic acid；Fmoc-Asp(OAl)-OH；(S)-2-((((9H-fluoren-9-yl)methoxy)carbonyl)amino)-4-(allyloxy)-4-oxobutanoic acid；N-α-(9-fluorenylmethoxycarbonyl)-L-aspartic acid β-allyl ester；Fmoc-Asp(All)
• CAS: 146982-24-3
• 化学式: C₂₂H₂₁NO₆
• 分子量: 395.412
• InChiKey: FBNFRRNBFASDKS-IBGZPJMESA-N

物化性质

• 熔点：
  111-115 °C
• 沸点：
  638.5±55.0 °C(Predicted)
• 密度：
  1.286±0.06 g/cm3(Predicted)
• 溶解度：
  溶于水或1%醋酸

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.23
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 安全说明：
  S22
• WGK Germany：
  3
• 海关编码：
  2924 29 70
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  2-8°C

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Fmoc-Asp(OAll)-OH
Synonyms:

---

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

---

Section 3. Composition/information on ingredients.
Ingredient name: Fmoc-Asp(OAll)-OH
CAS number: 146982-24-3

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C22H21NO6
Molecular weight: 395.4

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

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

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

用途

N-芴甲氧羰基-L-天冬氨酸4-烯丙酯是一种天冬氨酸衍生物，在医药和食品领域有着广泛的应用。

制备方法

1. 在三口瓶中，将四氢呋喃与天冬氨酸混合，然后在低温下滴加氧氯化磷。反应6小时后进行过滤，得到固体中间体。
2. 使用无水乙醚洗涤固体中间体，并烘干。随后将其与丙烯醇反应，在控制温度和时间的条件下完成反应，反应结束后用三乙胺调节pH值至7，促使固体析出。
3. 经过乙醚洗涤和干燥后，得到中间体L-Asp-0A11。
4. 将L-Asp-0A11溶解在碳酸氢钠溶液中，加入丙酮与Fmoc-0Su，并控制pH值约9，低温下反应3小时。
5. 反应完成后，用无水乙醚洗涤。通过醋酸乙酯进行产品提取，经过酸化、洗涤和干燥等步骤后浓缩至干。
6. 最终，使用石油醚结晶得到目标产物N-芴甲氧羰基-L-天冬氨酸4-烯丙酯。

反应信息

• 作为反应物：
  描述：

  Fmoc-L-天冬氨酸 4-烯丙酯 在 magnesium iodide 作用下， 以 四氢呋喃 为溶剂， 反应 1.0h， 以94%的产率得到Fmoc-L-天冬氨酸
  参考文献：
  名称：

  MgI2介导的保护基团的化学选择性切割：常规脱保护方法的替代方法

  摘要：

  在此描述了MgI 2作为定量和轻度化学选择性切割保护基的有价值工具的范围。这种新颖的合成方法扩大了保护基的使用范围，拓宽了合成过程中正交性的概念，并提供了从固体载体上释放化合物的简便机会。

  DOI：

  10.1002/chem.201501799
• 作为产物：
  描述：

  Fmoc-Asp-(OAll)-OH 在 Alcalase-cross-linked-enzyme-aggregates 作用下， 以 叔丁醇 为溶剂， 反应 16.0h， 以77%的产率得到Fmoc-L-天冬氨酸 4-烯丙酯
  参考文献：
  名称：

  A versatile and selective chemo-enzymatic synthesis of β-protected aspartic and γ-protected glutamic acid derivatives

  摘要：

  Two versatile, high yielding, and efficient chemo-enzymatic methods for the synthesis of beta-protected Asp and gamma-protected Glu derivatives using Alcalase are described. The first method is based on the alpha-selective enzymatic hydrolysis of symmetrical aspartyl and glutamyl diesters. The second method involving mixed diesters comprises a three-step protocol using (i) alpha-selective enzymatic methyl-esterification, (ii) chemical beta-esterification, and finally (iii) alpha-selective enzymatic methyl ester hydrolysis. The yields of the purified beta- and gamma-esters range from 77% to 91%. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2009.03.130

文献信息

• [EN] DIRECTED CONJUGATION TECHNOLOGIES<br/>[FR] TECHNOLOGIES DE CONJUGAISON DIRIGÉE
  申请人：KLEO PHARMACEUTICALS INC

  公开号：WO2021102052A1

  公开（公告）日：2021-05-27

  Among other things, the present disclosure provides technologies for site-directed conjugation of various moieties of interest to target agents. In some embodiments, the present disclosure utilizes target binding moieties to provide high conjugation efficiency and selectivity. In some embodiments, provided technologies are useful for preparing antibody conjugates.

  本公开提供了用于将各种感兴趣的分子与目标剂进行定点偶联的技术。在某些实施方式中，本公开利用目标结合分子以提供高偶联效率和选择性。在某些实施方式中，所提供的技术可用于制备抗体偶联物。
• Dipeptidyl Peptidase IV Dependent Water-Soluble Prodrugs of Highly Lipophilic Bicyclic Nucleoside Analogues
  作者：Alberto Diez-Torrubia、Jan Balzarini、Graciela Andrei、Robert Snoeck、Ingrid De Meester、María-José Camarasa、Sonsoles Velázquez

  DOI：10.1021/jm101624e

  日期：2011.3.24

  upon selective conversion by purified DPPIV/CD26 and by soluble DPPIV/CD26 present in bovine, murine, and human serum. Vildagliptin, a specific inhibitor of DPPIV/CD26, was able to completely block the hydrolysis of the prodrugs in the presence of purified DPPIV/CD26 human, murine, and bovine serum. Several novel prodrugs showed remarkable increases in water solubility (up to more than 3 orders of magnitude)

  我们提出基于二肽基肽酶IV（DPPIV / CD26）的前药方法在含羟基药物衍生物中的首次报道。特别是，我们将此策略应用于双环呋喃并嘧啶核苷类似物（BCNA）的高度亲脂性抗病毒药物家族，以改善其理化和药代动力学特性。我们的稳定性数据表明，通过纯化的DPPIV / CD26和存在于牛，鼠和人血清中的可溶性DPPIV / CD26的选择性转化，前药可有效释放母体BCNA药物。维达列汀，一种DPPIV / CD26的特异性抑制剂，在纯化的DPPIV / CD26人，鼠和牛血清的存在下能够完全阻断前药的水解。与难溶性母体药物相比，几种新颖的前药显示出水溶性的显着提高（最高超过3个数量级）。我们还证明了与小鼠母体药物相比，前药的口服生物利用度显着提高。
• Amphiphilic peptide-based MMP3 inhibitors for intra-articular treatment of knee OA
  作者：Cristian Guarise、Davide Ceradini、Martina Tessari、Mauro Pavan、Stefano Moro、Veronica Salmaso、Carlo Barbera、Riccardo Beninatto、Devis Galesso

  DOI：10.1016/j.bmc.2021.116132

  日期：2021.5

  interactive cycles of design, synthesis and screening, accompanied by computational evaluation and optimization. Two MMP3Is, e(I) and l(II), were selected because of their effective inhibitory activity (3.2 and 10.2 µM, respectively) and water solubility. Both MMPIs showed a broad range of inhibitory effects against almost all the MMPs tested. In an in vitro model of inflammatory OA, e(I) was the most effective

  自 2007 年以来，金属蛋白酶 (MMP) 被认为是治疗骨关节炎 (OA) 的潜在目标，其主要致病事件是关节软骨的广泛退化。MMP3 是一种对这些退行性变化至关重要的酶。然而，在 MMPs 抑制剂 (MMPIs) 的临床试验期间，选择性、低生物利用度和不良代谢特征的问题导致有限的有益效果，因此没有理由进一步开展临床研究。在之前的一项工作中，一种新的透明质酸 (HA) 烷基衍生物 HYADD4®，之前被批准用于膝关节 OA 的关节内治疗，在体外和体内进行了研究作为 MMP3I。分子模拟研究证实了这种 HA 衍生物的烷基侧链与 MMP3 的额外 S1' 口袋之间的相互作用。然而，HYADD4® 的高分子量和极性 HA 骨架意味着高去溶剂化能量成本，这可能会降低其抑制效力。在这项研究中，通过设计、合成和筛选的交互循环，以及计算评估和优化，开发了一类基于小肽主链 (CGV) 化学衍生的新型 MMP3Is。选择了两种
• [EN] BETA-HAIRPIN PEPTIDOMIMETICS<br/>[FR] PEPTIDOMIMÉTIQUES EN ÉPINGLE À CHEVEUX BÊTA
  申请人：POLYPHOR AG

  公开号：WO2016150576A1

  公开（公告）日：2016-09-29

  Beta-hairpin peptidomimetics of the general formula (I), and pharmaceutically acceptable salts thereof, with P, T, Q., and optionally L being elements as defined in the description and the claims, have Gram-negative antimicrobial activity to e.g. inhibit the growth or to kill microorganisms such as Klebsiellapneumoniae and/or Acinetobacter baumannii and/or Escherichia coli and/or Pseudomonas aeruginosa. They ca n be used as medicaments to treat or prevent infections or as disinfectants for foodstuffs, cosmetics, medicaments or other nutrient-containing materials. These peptidomimetics can be manufactured by a process which is based on a mixed solid- and solution phase synthetic strategy.

  Beta-发夹仿生肽的一般公式（I），及其药学上可接受的盐，其中P、T、Q.，以及可选的L作为描述和权利要求中定义的元素，具有抗革兰氏阴性微生物活性，例如抑制生长或杀灭肺炎克雷伯菌、包括鲍曼不动杆菌、大肠杆菌和铜绿假单胞菌等微生物。它们可用作药物治疗或预防感染，或用作食品、化妆品、药物或其他含营养物质的材料的消毒剂。这些仿生肽可以通过基于混合固相和溶液相合成策略的过程制造。
• 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。