N-甲氧羰基-L-叔亮氨酸 | 162537-11-3

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 亮氨酸类衍生物
• 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-甲氧羰基-L-叔亮氨酸
• 中文别名: MOC-L-叔亮氨酸；N-MOC-L-叔亮氨酸；N-甲氧基-L-叔亮氨基酸
• 英文名称: (S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid
• 英文别名: N-methoxycarbonyl-L-tert-leucine；(S)-2-(methoxycarbonylamino)-3,3-dimethylbutyric acid；(S)-2-((Methoxycarbonyl)amino)-3,3-dimethylbutanoic acid；(2S)-2-(methoxycarbonylamino)-3,3-dimethylbutanoic acid
• CAS: 162537-11-3
• 化学式: C₈H₁₅NO₄
• 分子量: 189.211
• InChiKey: NWPRXAIYBULIEI-RXMQYKEDSA-N

物化性质

• 熔点：
  1090C
• 沸点：
  320.9±25.0 °C(Predicted)
• 密度：
  1.126±0.06 g/cm3(Predicted)
• 溶解度：
  溶于乙酸乙酯和甲醇。
• LogP：
  0.832 at 21℃

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  13
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  75.6
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 海关编码：
  2924199090
• WGK Germany：
  1
• 危险性防范说明：
  P261,P305+P351+P338
• 危险性描述：
  H315,H319,H335
• 储存条件：
  室温

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Methoxycarbonyl-L-tert-Leucine
Product Name:
Synonyms:

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Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.
H315: Causes skin irritation
H319: Causes serious eye irritation
H335: May cause respiratory irritation
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
Wear protective gloves/protective clothing/eye protection/face protection
P280:
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing
P304+P340: IF INHALED: Remove victim to fresh air and keep at rest in a position comfortable for breathing
P405: Store locked up

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Section 3. Composition/information on ingredients.
Methoxycarbonyl-L-tert-Leucine
Ingredient name:
CAS number: 162537-11-3

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Section 4. First aid measures
Immediately wash skin with copious amounts of water for at least 15 minutes while removing
Skin contact:
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.
Wash out mouth with copious amounts of water for at least 15 minutes. Seek medical attention.
Ingestion:

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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.
Storage: Store in closed vessels, refrigerated.

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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
Not specified
Appearance:
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C8H15NO4
Molecular weight: 189.2

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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

制备方法与用途

应用 N-甲氧羰基-L-叔亮氨酸可作为有机合成中间体和医药中间体，主要用于实验室研发和化工生产过程中。

制备 将8克L-丙氨酸（168毫摩尔）溶解在168毫升1N NaOH溶液中，并加入8.9克Na2CO3（84毫摩尔）。将该溶液冷却至0°C，然后逐滴加入20.5毫升氯甲酸甲酯（172毫摩尔）。反应混合物在室温下搅拌3.5小时后，用乙醚洗涤，用1N HCl酸化至pH约为1。水层使用DCM萃取，有机层用盐水洗涤，再用Na2SO4干燥并浓缩，最终得到目标中间体N-甲氧羰基-L-叔亮氨酸。

反应信息

• 作为反应物：
  描述：

  N-甲氧羰基-L-叔亮氨酸 在 N-甲基吗啉 、 lithium tri-t-butoxyaluminum hydride 、 sodium iodide 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 、 乙醚 、 乙腈 为溶剂， 反应 4.5h， 生成 阿扎那韦
  参考文献：
  名称：

  通过高度非对映选择性还原方法高效，实用地合成HIV蛋白酶抑制剂Atazanavir

  摘要：

  通过采用非对映选择性还原酮亚甲基氮杂-二肽等排物10作为关键和最终步骤，开发了一种有效且实用的HIV-1蛋白酶抑制剂Atazanavir合成方法。通过Felkin -Anh控制，由于笨重和手性的N -（-）的结果，通过三叔丁氧基氢化铝锂在乙醚中还原氨基酮的高非对映选择性，从而得到所需的顺式1,2-氨基醇结构。甲氧基羰基） -升-叔-leucinyl部分为氮保护基团。两个关键中间体的联接器，ñ - （甲氧羰基） -升-叔亮氨酸酰化的苄基肼7和氯甲基酮9通过S N 2反应在我们优化的条件下以高收率提供了氨基酮10。我们的新方法提供了引入末的小号羟基基团和苄基肼和氯甲基酮与早期酰化Ñ - （甲氧羰基） -升-叔-亮氨酸，分别，其赋予高效率和容易纯化。

  DOI：

  10.1021/op7001563
• 作为产物：
  描述：

  N-Boc-L-叔亮氨酸 在 盐酸 、 sodium hydroxide 作用下， 以 水 、 甲苯 为溶剂， 反应 5.0h， 生成 N-甲氧羰基-L-叔亮氨酸
  参考文献：
  名称：

  EP2423187

  摘要：

  公开号：

文献信息

• HEPATITIS C VIRUS INHIBITORS AND USES THEREOF IN PREPARATION OF DRUGS
  申请人：CHANGZHOU YINSHENG PHARMACEUTICAL CO., LTD.

  公开号：US20170253614A1

  公开（公告）日：2017-09-07

  A series of hepatitis C virus (HCV) inhibitors and compositions and applications thereof in the preparation of drugs for treating chronic HCV infection. Especially, a series of compounds that are used as NS5A inhibitors, and compositions and uses thereof in the preparations of drugs.

  一系列丙型肝炎病毒（HCV）抑制剂及其组合物，以及在制备用于治疗慢性HCV感染的药物时的应用。特别是一系列用作NS5A抑制剂的化合物，以及在药物制剂中的组合物和用途。
• Anti-Viral Compounds
  申请人：DeGoey David A.

  公开号：US20100317568A1

  公开（公告）日：2010-12-16

  Compounds effective in inhibiting replication of Hepatitis C virus (“HCV”) are described. This invention also relates to processes of making such compounds, compositions comprising such compounds, and methods of using such compounds to treat HCV infection.

  描述了一种有效抑制丙型肝炎病毒（“HCV”）复制的化合物。本发明还涉及制备这种化合物的方法、包含这种化合物的组合物，以及使用这种化合物治疗HCV感染的方法。
• Coupling of an Acyl Migration Prodrug Strategy with Bio-activation To Improve Oral Delivery of the HIV-1 Protease Inhibitor Atazanavir
  作者：Murugaiah A. M. Subbaiah、Nicholas A. Meanwell、John F. Kadow、Lakshumanan Subramani、Mathiazhagan Annadurai、Thangeswaran Ramar、Salil D. Desai、Sarmistha Sinha、Murali Subramanian、Sandhya Mandlekar、Srikanth Sridhar、Shweta Padmanabhan、Priyadeep Bhutani、Rambabu Arla、Susan M. Jenkins、Mark R. Krystal、Chunfu Wang、Ramakanth Sarabu

  DOI：10.1021/acs.jmedchem.8b00277

  日期：2018.5.10

  they are characterized by poor oral bioavailability and a need for boosting with a pharmacokinetic enhancer, which results in additional drug–drug interactions that are sometimes difficult to manage. We investigated a chemo-activated, acyl migration-based prodrug design approach to improve the pharmacokinetic profile of 1 but failed to obtain improved oral bioavailability over dosing the parent drug

  HIV-1蛋白酶抑制剂（PIs）包括atazanavir（ATV，1）仍然是治疗HIV-1感染的重要药物。但是，它们的特点是口服生物利用度差，并且需要使用药代动力学增强剂进行增强，从而导致有时难以管理的其他药物相互作用。我们研究了一种基于化学活化，酰基转移的前药设计方法，以改善1的药代动力学。但与给大鼠服用母体药物相比，口服生物利用度没有提高。通过将胺与旨在进行生物活化的蛋白缀合来完善此策略，以作为调节后续化学活化的手段。这最终导致在铅前体药物：（1）产生的显着更好的口服药物递送1相对于亲本本身，简单的基于酰基迁移的前药，和相应的简单，当升-Val前药，（2）充当一个贮库，其导致母体药物在体内的持续释放，并且（3）具有减轻与1相关的pH依赖性吸收的好处，从而潜在地降低了同时使用降低胃酸的药物导致生物利用度降低的风险。
• [EN] CHEMICAL COMPOUNDS<br/>[FR] COMPOSÉS CHIMIQUES
  申请人：GLAXOSMITHKLINE LLC

  公开号：WO2011050146A1

  公开（公告）日：2011-04-28

  Disclosed are compounds of Formula (I). Also disclosed are pharmaceutical compositions comprising the compounds, and methods for treating HCV invention by administration of the compounds.

  揭示了化合物的化学式（I）。还揭示了包含这些化合物的药物组合物，以及通过给药这些化合物来治疗HCV的方法。
• [EN] HIV PROTEASE INHIBITING COMPOUNDS<br/>[FR] COMPOSES INHIBITEURS DE LA PROTEASE DU VIH
  申请人：ABBOTT LAB

  公开号：WO2005061487A1

  公开（公告）日：2005-07-07

  A compound of the formula (I) is disclosed as an HIV protease inhibitor. Methods and compositions for inhibiting an HIV infection are also disclosed.

  公开了一种公式(I)的化合物作为HIV蛋白酶抑制剂。还公开了用于抑制HIV感染的方法和组合物。