N-苄氧羰基-L-苯丙氨酰基-L-苯丙氨酸 | 13122-91-3

• 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-苄氧羰基-L-苯丙氨酰基-L-苯丙氨酸
• 中文别名: N-苄氧羰基-L-苯内氨酰基-L-半胱氨酸；3-苯基-N-[3-苯基-N-[(苯基甲氧基)羰基]-L-丙氨酰]-L-丙氨酸
• 英文名称: N-benzyloxycarbonyl-L-phenylalanyl-L-phenylalanine
• 英文别名: Z-Phe-Phe-OH；Cbz-L-Phe-L-Phe-OH；(S)-2-((S)-2-(((benzyloxy)carbonyl)amino)-3-phenylpropanamido)-3-phenylpropanoic acid；3-Phenyl-N-(3-phenyl-N-((phenylmethoxy)carbonyl)-L-alanyl)-L-alanine；(2S)-3-phenyl-2-[[(2S)-3-phenyl-2-(phenylmethoxycarbonylamino)propanoyl]amino]propanoic acid
• CAS: 13122-91-3
• 化学式: C₂₆H₂₆N₂O₅
• 分子量: 446.503
• InChiKey: JNRHNGGTJOBXHL-GOTSBHOMSA-N

物化性质

• 熔点：
  159 °C
• 沸点：
  730.2±60.0 °C(Predicted)
• 密度：
  1.253±0.06 g/cm3(Predicted)
• 溶解度：
  在甲醇中几乎透明

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  33
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  105
• 氢给体数：
  3
• 氢受体数：
  5

安全信息

• 储存条件：
  -15°C

SDS

N-Carbobenzoxy-L-phenylalanyl-L-phenylalanine
SAFETY DATA SHEET

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Section 1. IDENTIFICATION
Product name: N-Carbobenzoxy-L-phenylalanyl-L-phenylalanine

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Section 2. HAZARDS IDENTIFICATION
GHS classification
PHYSICAL HAZARDS Not classified
Not classified
HEALTH HAZARDS
ENVIRONMENTAL HAZARDS Not classified
GHS label elements, including precautionary statements
Pictograms or hazard symbols None
No signal word
Signal word
Hazard statements None
None
Precautionary statements:

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substance/mixture: Substance
Components: N-Carbobenzoxy-L-phenylalanyl-L-phenylalanine
Percent: >98.0%(T)
CAS Number: 13122-91-3
Synonyms: N-Cbz-L-phenylalanyl-L-phenylalanine , Z-Phe-Phe-OH
Chemical Formula: C26H26N2O5

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Section 4. FIRST AID MEASURES
Inhalation: Remove victim to fresh air and keep at rest in a position comfortable for breathing.
Get medical advice/attention if you feel unwell.
Skin contact: Remove/Take off immediately all contaminated clothing. Rinse skin with
water/shower. If skin irritation or rash occurs: Get medical advice/attention.
Eye contact: Rinse cautiously with water for several minutes. Remove contact lenses, if present
and easy to do. Continue rinsing. If eye irritation persists: Get medical
advice/attention.
Ingestion: Get medical advice/attention if you feel unwell. Rinse mouth.
Protection of first-aiders: A rescuer should wear personal protective equipment, such as rubber gloves and air-
tight goggles.

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Section 5. FIRE-FIGHTING MEASURES
Suitable extinguishing Dry chemical, foam, water spray, carbon dioxide.
media:
Specific hazards arising Take care as it may decompose upon combustion or in high temperatures to
from the chemical: generate poisonous fume.
N-Carbobenzoxy-L-phenylalanyl-L-
phenylalanine

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Section 5. FIRE-FIGHTING MEASURES
Precautions for firefighters: Fire-extinguishing work is done from the windward and the suitable fire-extinguishing
method according to the surrounding situation is used. Uninvolved persons should
evacuate to a safe place. In case of fire in the surroundings: Remove movable
containers if safe to do so.
Special protective When extinguishing fire, be sure to wear personal protective equipment.
equipment for firefighters:

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Section 6. ACCIDENTAL RELEASE MEASURES
Use personal protective equipment. Keep people away from and upwind of spill/leak.
Personal precautions,
protective equipment and Entry to non-involved personnel should be controlled around the leakage area by
emergency procedures: roping off, etc.
Environmental precautions: Prevent product from entering drains.
Methods and materials for Sweep dust to collect it into an airtight container, taking care not to disperse it.
containment and cleaning Adhered or collected material should be promptly disposed of, in accordance with
up: appropriate laws and regulations.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Handling is performed in a well ventilated place. Wear suitable protective equipment.
Technical measures:
Prevent dispersion of dust. Wash hands and face thoroughly after handling.
Use a local exhaust if dust or aerosol will be generated.
Advice on safe handling: Avoid contact with skin, eyes and clothing.
Conditions for safe storage, including any
incompatibilities
Storage conditions: Keep container tightly closed. Store in a cool and dark place.
Store away from incompatible materials such as oxidizing agents.
Packaging material: Comply with laws.

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Section 8. EXPOSURE CONTROLS / PERSONAL PROTECTION
Install a closed system or local exhaust as possible so that workers should not be
Engineering controls:
exposed directly. Also install safety shower and eye bath.
Personal protective equipment
Respiratory protection: Dust respirator. Follow local and national regulations.
Hand protection: Protective gloves.
Eye protection: Safety glasses. A face-shield, if the situation requires.
Skin and body protection: Protective clothing. Protective boots, if the situation requires.

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Physical state (20°C): Solid
Form: Crystal- Powder
White - Almost white
Colour:
Odour: No data available
pH: No data available
Melting point/freezing point:159°C
No data available
Boiling point/range:
Flash point: No data available
Flammability or explosive
limits:
No data available
Lower:
Upper: No data available
No data available
Relative density:
Solubility(ies):
No data available
[Water]
[Other solvents] No data available
N-Carbobenzoxy-L-phenylalanyl-L-
phenylalanine

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Section 10. STABILITY AND REACTIVITY
Chemical stability: Stable under proper conditions.
Possibility of hazardous No special reactivity has been reported.
reactions:
Incompatible materials: Oxidizing agents
Hazardous decomposition Carbon monoxide, Carbon dioxide, Nitrogen oxides (NOx)
products:

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Section 11. TOXICOLOGICAL INFORMATION
No data available
Acute Toxicity:
Skin corrosion/irritation: No data available
No data available
Serious eye
damage/irritation:
Germ cell mutagenicity: No data available
Carcinogenicity:
No data available
IARC =
NTP = No data available
No data available
Reproductive toxicity:

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Section 12. ECOLOGICAL INFORMATION
Ecotoxicity:
Fish: No data available
Crustacea: No data available
Algae: No data available
Persistence / degradability: No data available
Bioaccumulative No data available
potential(BCF):
Mobility in soil
Log Pow: No data available
Soil adsorption (Koc): No data available
Henry's Law No data available
constant(PaM3/mol):

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Section 13. DISPOSAL CONSIDERATIONS
Recycle to process, if possible. Consult your local regional authorities. You may be able to dissolve or mix material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber system.
Observe all federal, state and local regulations when disposing of the substance.

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Section 14. TRANSPORT INFORMATION
Hazards Class: Does not correspond to the classification standard of the United Nations
UN-No: Not listed

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Section 15. REGULATORY INFORMATION
Safe management ordinance of dangerous chemical product (State Council announces on January 26, 2002
and revised on February 16,2011): Safe use and production, the storage of a dangerous chemical, transport,
loading and unloading were prescribed.
N-Carbobenzoxy-L-phenylalanyl-L-
phenylalanine

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SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  N-苄氧羰基-L-苯丙氨酰基-L-苯丙氨酸 在 tris(dibenzylideneacetone)dipalladium (0) Cu(I) thiophenecarboxylate 、 1-羟基苯并三唑 、 N,N'-二环己基碳二亚胺 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 乙酸乙酯 为溶剂， 反应 3.0h， 生成 (-)-2-(S)-benzyloxycarbonylamino-N-(1-(S)-benzyl-2-oxo-4-phenyl-but-3-enyl)-3-phenyl-propionamide
  参考文献：
  名称：

  肽基硫醇酯-硼酸交叉偶联法在常温下合成高对映纯度N保护的肽基酮

  摘要：

  在化学计量的 Cu(I) 噻吩-2-羧酸盐和催化作用下，衍生自 N-保护的单肽、二肽和三肽的 α-氨基酸硫羟酸酯与芳基、富含 π 电子的杂芳基或烯基硼酸偶联Pd(2)(dba)(3)/亚磷酸三乙酯生成相应的 N 保护肽基酮，产率和对映体纯度都非常好。亚磷酸三乙酯通过减轻不希望的钯催化脱羰-β-消除α-氨基硫羟酸酯，作为支持配体发挥关键作用。肽基酮的合成在室温下非碱性条件下进行，并表现出对功能的高度耐受性。

  DOI：

  10.1021/ja0658719
• 作为产物：
  描述：

  N-(benzyloxycarbonyl)-L-phenylalanyl-L-phenylalanine methyl ester 在 sodium hydroxide 作用下， 生成 N-苄氧羰基-L-苯丙氨酰基-L-苯丙氨酸
  参考文献：
  名称：

  Effects of Normal and Their Branched Alcohols with Structurally Minimal Variation on Kinetic Parameters in Thermolysin-catalyzed Peptide Hydrolysis and Synthesis ofN-(Benzyloxycarbonyl)-L-phenylalanyl-L-phenylalanine and Its Methyl Ester

  摘要：

  当在反应介质中加入较高的醇类溶剂时，在热溶解酶催化肽水解和合成过程中观察到酶活性增强，随后酶活性降低，最后失活。所使用的有机溶剂含量低于缓冲液（即水有机单相体系）中的饱和浓度。在这些反应中，当酒精浓度达到最大酶活性时，动力学参数 Km 和 kcat 随酒精对数 P 值的增加而线性变化，因此 kcat/Km 也随之增加。当使用对数 P 值理论上相等的结构变化最小的醇的支链异构体作为附件时，动力学参数也发生了变化。这些结果，尤其是每种有机溶剂的 Km 变化，表明每种醇都以其自身的有效模式作用于酶的活性位点。

  DOI：

  10.1271/bbb.59.535

文献信息

• <i>α-N</i>-Protected dipeptide acids: a simple and efficient synthesis via the easily accessible mixed anhydride method using free amino acids in DMSO and tetrabutylammonium hydroxide
  作者：G. Verardo、A. Gorassini

  DOI：10.1002/psc.2503

  日期：2013.5

  to find simple and efficient methods for their synthesis. For this reason, we have investigated the synthesis of α‐N‐protected dipeptide acids by reacting the easily accessible mixed anhydride of α‐N‐protected amino acids with free amino acids under different reaction conditions. The combination of TBA‐OH and DMSO has been found to be the best to overcome the low solubility of amino acids in organic

  在医学和药理学领域中，二肽的重要性已得到充分证明，并且已进行了许多努力来寻找简单有效的合成方法。因此，我们通过使易于获得的α-N混合酸酐反应，研究了α-N保护的二肽酸的合成在不同的反应条件下用游离氨基酸保护氨基酸。已经发现，TBA-OH和DMSO的组合是克服氨基酸在有机溶剂中低溶解度的最佳方法。在这些实验条件下，均相缩合反应迅速发生且没有可检测的差向异构。本方法也适用于未保护的侧链Tyr，Trp，Glu和Asp，但不适用于Lys。后一个残基能够结合两个混合酸酐分子，得到相应的异三肽。此外，已经测试了该方案对三肽和四肽合成的适用性。这种方法减少了对保护基的需求，具有成本效益，可扩展性，并产生了可用作较大肽合成的基础材料的二肽酸。
• 4-(4,6-Dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium Toluene-4-sulfonate (DMT/NMM/TsO⁻ ) Universal Coupling Reagent for Synthesis in Solution
  作者：Justyna Fraczyk、Zbigniew J. Kaminski、Joanna Katarzynska、Beata Kolesinska

  DOI：10.1002/hlca.201700187

  日期：2018.1

  environmentally‐friendly N‐triazinylammonium family of sulfonates, has been found to be a very effective coupling reagent for the synthesis of amides, esters and peptides in solution. This study confirms the usefulness of DMT/NMM/TsO− for peptide synthesis in solution, starting from Z‐, Fmoc‐, and Boc‐protected substrates as well as unnatural building blocks. Peptide synthesis with DMT/NMM/TsO− produced

  4-（4,6-二甲氧基-1,3,5-三嗪-2-基）-4-甲基吗啉的甲苯-4-磺酸酯（DMT / NMM / TSO - ），则廉价且环境友好的代表性构件Ñ磺酸的三叠氮基铵家族被发现是溶液中酰胺，酯和肽合成的非常有效的偶联剂。这项研究证实DMT / NMM / TSO的有用性-在溶液中的肽合成，从Z-，将Fmoc-，和起始Boc-保护的底物，以及不自然的构建块。用DMT / NMM / TSO进行肽合成-产量高，原油纯度高，外消旋化风险低。在所有情况下，都使用化学计量的试剂和标准的合成程序，而无需耗时的优化阶段或昂贵的色谱纯化。DMT / NMM / TSO -也被发现是用于使用片段偶联策略寡肽的合成中非常有用的。
• Sodium Borohydride Reduction of Carbamoyl Azide Function: A Synthesis of<i>N</i>-Protected<i>N′</i>-Formyl-<i>gem</i>-diaminoalkyl Derivatives
  作者：Giancarlo Verardo、Andrea Gorassini

  DOI：10.1002/ejoc.201300442

  日期：2013.8

  reduction of the carbamoyl azide of α-N-Boc/Fmoc/Z-protected amino acids and dipeptides (Boc = tert-butoxycarbonyl, Fmoc = 9-fluorenylmethoxycarbonyl, Z = benzyloxycarbonyl) by treatment with NaBH4 at room temperature. The reaction proceeds rapidly (45 min) without detectable epimerization (by HPLC-ESI-MS analysis) and is not influenced by the nature of the starting carbamoyl azide. The 1H and 13C NMR

  报道了 N-保护的 N'-甲酰基-宝石-二氨基烷基衍生物的简单、有效的两步合成。该程序涉及通过在室温下用 NaBH4 处理，前所未有地还原 α-N-Boc/Fmoc/Z 保护的氨基酸和二肽（Boc = 叔丁氧基羰基，Fmoc = 9-芴基甲氧基羰基，Z = 苄氧基羰基）的氨基甲酰基叠氮化物. 反应进行得很快（45 分钟），没有可检测到的差向异构化（通过 HPLC-ESI-MS 分析），并且不受起始氨基甲酰叠氮化物的性质影响。合成的 N-保护的 N'-甲酰胺的 1H 和 13C NMR 分析在 [D6]DMSO 中进行。由于围绕 N-CO 甲酰基键的旋转受限，光谱显示溶液中存在两种旋转异构形式。两种异构体的 N-CH-N 质子的整合表明，顺式异构体（旋转异构体 B）是丰度更高的构象异构体 60% 到 78%。报道的合成代表了氨基甲酰基叠氮化物作为用于许多合成目的的通用手性起始材料的潜在价值。
• Highly Diastereoselective Peptide Chain Extensions of Unprotected Amino Acids with<i>N</i>-(Z-α-Aminoacyl)benzotriazoles
  作者：Alan R. Katritzky、Kazuyuki Suzuki、Sandeep K. Singh

  DOI：10.1055/s-2004-831255

  日期：——

  Coupling an unprotected amino acid or dipeptide in partially aqueous solution with a readily available N-(Z-α-amino­acyl)benzotriazole or N-(Z-α-aminopetidoyl)benzotriazole affords N-terminal-protected di-, tri-, and tetrapeptides in yields of 85-98% (average 95% for 2a-i, 93% for 4a-f and 4a′, 86% for 5a-b) with minimal epimerization.

  在部分含水溶液中，将未保护的氨基酸或二肽与易得的N-(Z-α-氨基酰基)苯并三唑或N-(Z-α-氨基肽酰基)苯并三唑结合，可以以85-98%的产率（平均产率分别为2a-i的95%，4a-f和4a′的93%，5a-b的86%）获得N端保护的二肽、三肽和四肽，且消旋化程度最小。
• Phenylalanine derivatives enhancing intestinal absorption of insulin in mice.
  作者：YUSUKE AMINO、KAZUHIRO KAWADA、KOJI TOI、IZUMI KUMASHIRO、KOJI FUKUSHIMA

  DOI：10.1248/cpb.36.4426

  日期：——

  The adjuvant effect of N-acyl-L-and D-phenylalanine derivatives on intestinal absorption of insulin was investigated in normal mice. The correlation between the chemical structural properties of the N-acyl moiety and the absorption-promoting activity was estimated from the glucose concentrations and the insulin levels in the blood of mice after oral combined administration of insulin and adjuvant. The chemical structural properties of N-acyl-phenylalanine derivatives necessary for adjuvant effect on intestinal absorption of insulin were as follows. 1. An aromatic ring is present, separated by two atoms from the acyl carbonyl group. 2. Either of X or Y is oxygen or X-Y is a double bond in Fig.2. 3. The N-acyl moiety has small hydrophobic substituents, such as F, Cl, or Me at Rα, Rβ, Rη and has an appropriate hydrophilic-hydrophobic balance of the overall molecule. The use of these agents to enhance insulin absorption offers the possibility of a new approach to oral insulin therapy.

  研究了N-酰基-L-和D-苯丙氨酸衍生物对正常小鼠胰岛素肠道吸收的辅助效应。根据小鼠口服胰岛素和辅料联合给药后的血糖浓度和胰岛素水平，推测了N-酰基部分的化学结构性质与促吸收活性之间的相关性。N-酰基-苯丙氨酸衍生物对胰岛素肠道吸收具有辅效应的化学结构性质如下：1. 芳环存在，与酰基羰基相隔两个原子。2. 图2中的X或Y之一为氧，或者X-Y是双键。3. N-酰基部分具有较小的疏水取代基，如F、Cl或Me在Rα、Rβ、Rη位置，并且整个分子具有适当的亲水-疏水平衡。利用这些制剂增强胰岛素吸收，为口服胰岛素治疗提供了新的途径。

表征谱图