(S)-2-Fmoc-氨基辛二酸 8-叔丁酯 | 276869-41-1

• 物质功能分类: 有机原料 - 羧酸类化合物及衍生物 - 羧酸酯及其衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 芴
• 中文名称: (S)-2-Fmoc-氨基辛二酸 8-叔丁酯
• 中文别名: (S)-2-Fmoc-氨基辛二酸8-叔丁酯；(S)-2-FMOC-氨基辛二酸8-叔丁酯；(S)-Fmoc-2-氨基辛二酸8-叔丁酯；(S)-2-Fmoc-氨基辛二酸-8-叔丁酯；(S)-2-FMOC-氨基辛二酸 8-叔丁酯
• 英文名称: (S)-Fmoc-Asu(OtBu)-OH
• 英文别名: (S)-2-((((9H-Fluoren-9-yl)methoxy)carbonyl)amino)-8-(tert-butoxy)-8-oxooctanoic acid；(2S)-2-(9H-fluoren-9-ylmethoxycarbonylamino)-8-[(2-methylpropan-2-yl)oxy]-8-oxooctanoic acid
• CAS: 276869-41-1
• 化学式: C₂₇H₃₃NO₆
• mdl: MFCD00080269
• 分子量: 467.562
• InChiKey: ULPCAXORIFXUMN-QHCPKHFHSA-N

物化性质

• 沸点：
  633.8±55.0 °C(Predicted)
• 密度：
  1.184±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  34
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.444
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

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-asu(otbu)-oh
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-asu(otbu)-oh
CAS number: 276869-41-1

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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: C27H33NO6
Molecular weight: 467.6

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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：

  (S)-2-Fmoc-氨基辛二酸 8-叔丁酯 在 碳酸氢钠 、 三氟乙酸 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 1.0h， 生成 2-(9H-fluoren-9-ylmethoxycarbonylamino)-octanedioic acid 1-allyl ester
  参考文献：
  名称：

  通过平行合成衍生自α-氨基异丁烯酸的抗癌药的设计，合成，效能和细胞选择性。

  摘要：

  上个世纪的化学疗法的特征是不能区分癌细胞和正常细胞类型的细胞毒性药物，因此伴有通常限制剂量的毒性副作用。分化剂选择性杀死癌细胞或将其转化为非增殖或正常表型的能力可能导致细胞和组织特异性药物的产生，而没有当前癌症化学疗法的副作用。对于衍生自氨基酸的新一代组蛋白脱乙酰基酶抑制剂来说，这可能是可能的。现已报道了43种衍生自2-氨基磺酸的化合物的结构-活性关系，这些化合物可杀死多种癌细胞，其中26种是针对MM96L黑色素瘤细胞（IC50 20 nM-1 microM）的有效细胞毒素，而17种在杀死MM96L黑色素瘤细胞方面的选择性比正常（新生儿包皮成纤维细胞，NFF）细胞高5到60倍。与先前报道的衍生自半胱氨酸的化合物相比，这表示效力增加了10至100倍，并且选择性提高了多达10倍（J. Med。Chem。2004，47，2984）。选择性也被低估了，因为正常细胞NFF很少被所有药物杀死，这些药物

  DOI：

  10.1021/jm050214x
• 作为产物：
  描述：

  6-碘己酸叔丁酯 在 cobalt(II) chloride lithium hydroxide 、 sodium hydroxide 、 acylase I from Aspergillus melleus 、 水 、 sodium hydride 、 碳酸氢钠 、 lithium chloride 作用下， 以 四氢呋喃 、 phosphate buffer 、 乙醇 、 水 、 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 77.5h， 生成 (S)-2-Fmoc-氨基辛二酸 8-叔丁酯
  参考文献：
  名称：

  通过平行合成衍生自α-氨基异丁烯酸的抗癌药的设计，合成，效能和细胞选择性。

  摘要：

  上个世纪的化学疗法的特征是不能区分癌细胞和正常细胞类型的细胞毒性药物，因此伴有通常限制剂量的毒性副作用。分化剂选择性杀死癌细胞或将其转化为非增殖或正常表型的能力可能导致细胞和组织特异性药物的产生，而没有当前癌症化学疗法的副作用。对于衍生自氨基酸的新一代组蛋白脱乙酰基酶抑制剂来说，这可能是可能的。现已报道了43种衍生自2-氨基磺酸的化合物的结构-活性关系，这些化合物可杀死多种癌细胞，其中26种是针对MM96L黑色素瘤细胞（IC50 20 nM-1 microM）的有效细胞毒素，而17种在杀死MM96L黑色素瘤细胞方面的选择性比正常（新生儿包皮成纤维细胞，NFF）细胞高5到60倍。与先前报道的衍生自半胱氨酸的化合物相比，这表示效力增加了10至100倍，并且选择性提高了多达10倍（J. Med。Chem。2004，47，2984）。选择性也被低估了，因为正常细胞NFF很少被所有药物杀死，这些药物

  DOI：

  10.1021/jm050214x

文献信息

• GLYCOSYLATED PSMA INHIBITORS FOR IMAGING AND ENDORADIOTHERAPY
  申请人：Technische Universität München

  公开号：EP3494998A1

  公开（公告）日：2019-06-12

  The present disclosure relates to imaging and endoradiotherapy of diseases involving prostate-specific membrane antigen (PSMA). Provided are compounds which bind or inhibit PSMA and furthermore carry at least one moiety which is amenable to radiolabeling. Provided are also medical uses of such compounds.

  本公开涉及涉及前列腺特异性膜抗原（PSMA）相关疾病的成像和内放射治疗。提供了结合或抑制PSMA并且携带至少一个适合于放射标记的基团的化合物。还提供了这类化合物的医学用途。
• [EN] PSMA LIGANDS FOR IMAGING AND ENDORADIOTHERAPY<br/>[FR] LIGANDS DE PSMA POUR L'IMAGERIE ET L'ENDORADIOTHÉRAPIE
  申请人：UNIV MUENCHEN TECH

  公开号：WO2019115547A1

  公开（公告）日：2019-06-20

  The present disclosure relates to imaging and endoradiotherapy of diseases involving prostate-specific membrane antigen (PSMA). Provided are compounds which bind or inhibit PSMA and furthermore carry at least one moiety which is amenable to radiolabeling. Provided are also medical uses of such compounds.

  本公开涉及涉及前列腺特异性膜抗原（PSMA）相关疾病的成像和内放射治疗。提供了结合或抑制PSMA并且携带至少一个适合于放射标记的基团的化合物。还提供了这类化合物的医疗用途。
• Novel sirtuin inhibitory warheads derived from the N^ε-acetyl-lysine analog <scp>l</scp>-2-amino-7-carboxamidoheptanoic acid
  作者：Yanhua He、Lingling Yan、Wenwen Zang、Weiping Zheng

  DOI：10.1039/c5ob01721a

  日期：——

  Potent sirtuin inhibitory warheads respectively against SIRT1/2/3, SIRT5, and SIRT6 were identified in the current study among the carboxamide NH₂-alkylated analogs of our lead sirtuin inhibitory warhead l-2-amino-7-carboxamidoheptanoic acid.

  在当前研究中，我们在我们的主要sirtuin抑制剂头部的羧酰胺NH₂-烷基化类似物中分别发现了针对SIRT1/2/3、SIRT5和SIRT6的有效sirtuin抑制剂。
• PeIA-5466: A Novel Peptide Antagonist Containing Non-natural Amino Acids That Selectively Targets α3β2 Nicotinic Acetylcholine Receptors
  作者：Arik J. Hone、Fernando Fisher、Sean Christensen、Joanna Gajewiak、David Larkin、Paul Whiteaker、J. Michael McIntosh

  DOI：10.1021/acs.jmedchem.9b00566

  日期：2019.7.11

  were synthesized by replacing amino acid residues in the second disulfide loop with standard or nonstandard residues and assessing their activity on α3β2 and α6/α3β2β3 nAChRs heterologously expressed in Xenopus laevis oocytes. Asparagine11 was found to occupy a pivotal position, and when replaced with negatively charged amino acids, selectivity for α3β2 over α6/α3β2β3 nAChRs was substantially increased

  由于缺乏亚型选择性配体，从药理学上将α3β2烟碱型乙酰胆碱受体（nAChRs）与密切相关的亚型（尤其是α6β2）区分开来具有挑战性。我们创建了α-芋螺毒素（α-Ctx）PeIA的类似物，以鉴定可被利用来选择性提高α3β2nAChRs的效力和选择性的配体-受体相互作用。通过用标准或非标准残基替换第二个二硫键环中的氨基酸残基并评估它们对非洲爪蟾卵母细胞中异源表达的α3β2和α6/α3β2β3nAChRs的活性，合成了一系列PeIA类似物。发现天冬酰胺11占据关键位置，当用带负电荷的氨基酸代替时，相对于α6/α3β2β3nAChRs，α3β2的选择性大大提高。然后设计第二代肽以进一步提高效能和选择性。一种肽PeIA-5466在α3β2上的效力比α6/α3β2β3大约300倍，是迄今为止报道的对α3β2选择性最高的拮抗剂。
• Substrates and Cyclic Peptide Inhibitors of the Oligonucleotide‐Activated Sirtuin 7**
  作者：Julie E. Bolding、Alexander L. Nielsen、Iben Jensen、Tobias N. Hansen、Line A. Ryberg、Samuel T. Jameson、Pernille Harris、Günther H. J. Peters、John M. Denu、Joseph M. Rogers、Christian A. Olsen

  DOI：10.1002/anie.202314597

  日期：2023.12.4

  The sirtuins are NAD⁺‐dependent lysine deacylases, comprising seven isoforms (SIRT1–7) in humans, which are involved in the regulation of a plethora of biological processes, including gene expression and metabolism. The sirtuins share a common hydrolytic mechanism but display preferences for different ϵ‐N‐acyllysine substrates. SIRT7 deacetylates targets in nuclei and nucleoli but remains one of the lesser studied of the seven isoforms, in part due to a lack of chemical tools to specifically probe SIRT7 activity. Here we expressed SIRT7 and, using small‐angle X‐ray scattering, reveal SIRT7 to be a monomeric enzyme with a low degree of globular flexibility in solution. We developed a fluorogenic assay for investigation of the substrate preferences of SIRT7 and to evaluate compounds that modulate its activity. We report several mechanism‐based SIRT7 inhibitors as well as de novo cyclic peptide inhibitors selected from mRNA‐display library screening that exhibit selectivity for SIRT7 over other sirtuin isoforms, stabilize SIRT7 in cells, and cause an increase in the acetylation of H3 K18.

  摘要sirtuins是一种依赖于NAD+的赖氨酸脱乙酰酶，在人类中有7种同工酶（SIRT1-7），它们参与了大量生物过程的调控，包括基因表达和新陈代谢。sirtuins具有共同的水解机制，但对ϵ-N-酰基赖氨酸底物有不同的偏好。SIRT7 可使细胞核和核小体中的靶标去乙酰化，但仍是七种同工酶中研究较少的一种，部分原因是缺乏特异性探究 SIRT7 活性的化学工具。在这里，我们表达了 SIRT7，并利用小角 X 射线散射揭示了 SIRT7 是一种单体酶，在溶液中具有较低的球状柔性。我们开发了一种荧光测定法，用于研究 SIRT7 的底物偏好，并评估调节其活性的化合物。我们报告了几种基于机制的 SIRT7 抑制剂以及从 mRNA 显示库筛选出的新环肽抑制剂，它们对 SIRT7 比其他 sirtuin 同工酶具有选择性，能稳定细胞中的 SIRT7，并能增加 H3 K18 的乙酰化。