N-Boc-顺式-4-羟基-L-脯氨酸 | 87691-27-8

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 脯氨酸类衍生物
• 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-Boc-顺式-4-羟基-L-脯氨酸
• 中文别名: N-Boc-顺-4-羟基-L-脯氨酸；N-Boc-顺式-4-羟基吡咯烷-2-羧酸；N-叔丁氧羰基-顺式-4-羟基-L-脯氨酸；叔丁氧羰基-顺式-L-羟脯氨酸；CIS-BOC-L-HYP-OH
• 英文名称: N-tert-butoxycarbonyl-L-cis-4-hydroxyproline
• 英文别名: (2S,4S)-1-(tert-butoxycarbonyl)-4-hydroxypyrrolidine-2-carboxylic acid；Boc-L-hydroxyproline；N-Boc-cis-4-hydroxy-L-proline；(2S,4S)-4-hydroxy-1-[(2-methylpropan-2-yl)oxycarbonyl]pyrrolidine-2-carboxylic acid
• CAS: 87691-27-8
• 化学式: C₁₀H₁₇NO₅
• mdl: MFCD02094406
• 分子量: 231.249
• InChiKey: BENKAPCDIOILGV-BQBZGAKWSA-N

物化性质

• 熔点：
  146 °C (D) (lit.)
• 比旋光度：
  -50 º (c=0.67, MeOH)
• 沸点：
  390.9±42.0 °C(Predicted)
• 密度：
  1.312±0.06 g/cm3(Predicted)
• 稳定性/保质期：

  按规定使用和贮存的情况下，该物质不会分解，也不会与氧化物发生反应。

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  16
• 可旋转键数：
  3
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  87.1
• 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,N
• 安全说明：
  S26,S36/37,S60,S61
• 危险类别码：
  R50,R36/37/38
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险品运输编号：
  UN 3077 9 / PGIII
• 危险标志：
  GHS07,GHS09
• 危险性描述：
  H315,H319,H335,H400
• 危险性防范说明：
  P261,P273,P305 + P351 + P338
• 储存条件：
  在干燥、阴凉、密闭且充满惰性气体的环境中保存。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: N-Boc-cis-4-hydroxy-L-Proline
Synonyms: (2S,4S)-4-Hydroxypyrrolidine-1,2-dicarboxylic acid, 1-tert-butyl ester

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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
H400: Very toxic to aquatic life
P261: Avoid breathing dust/fume/gas/mist/vapours/spray
P273: Avoid release to the environment
P305+P351+P338: IF IN EYES: Rinse cautiously with water for several minutes. Remove contact lenses if present
and easy to do – continue rinsing

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Section 3. Composition/information on ingredients.
Ingredient name: N-Boc-cis-4-hydroxy-L-Proline
CAS number: 87691-27-8

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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.
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
Appearance: Not specified
Boiling point: No data
Melting point: No data
Flash point: No data
Density: No data
Molecular formula: C10 H17 NO5
Molecular weight: 231.2

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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

简介

N-Boc-顺式-4-羟基-L-脯氨酸的熔点为146°C（文献值），比旋光度为-50º（c=0.67, MeOH），沸点为390.9±42.0°C（预测值），密度为1.312±0.06g/cm³（预测值），酸度系数（pKa）为3.80±0.40（预测值）。脯氨酸衍生物N-Boc-顺式-4-羟基-L-脯氨酸是一类广泛应用于医药、农业和化学领域的关键有机功能化合物。

用途

作为一类重要的非天然氨基酸，N-Boc-顺式-4-羟基脯氨酸常用于肽的合成修饰，以提高对蛋白水解酶降解的抵抗力，调节生物活性肽以及作为不对称手性诱导剂的物理和生化特性。

合成方法

将市售（Aldrich）化合物6（525mg，4mmol）溶于10mL水中和5mL THF中。加入NaOH水溶液调节pH值至9-10。随后，将Boc酸酐（959mg，4.4mmol）溶解在2mL THF中并滴加至反应混合物中。继续用NaOH水溶液维持pH 9-10。完成后，使用稀HCl水溶液将反应酸化至pH为3，并用乙酸乙酯（EtOAc，2x）萃取。有机相经无水硫酸钠干燥后减压浓缩，得到Boc保护的脯氨酸（化合物6a）。该固体产物用己烷（3x）洗涤并真空干燥，最终获得中间体固体N-Boc-顺式-4-羟基-L-脯氨酸，产率为882mg，收率95%。

反应信息

• 作为反应物：
  描述：

  N-Boc-顺式-4-羟基-L-脯氨酸 在 盐酸 、 Jones reagent 、 聚合甲醛 、 三乙酰氧基硼氢化钠 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 、 甲苯 为溶剂， 生成 特力利汀
  参考文献：
  名称：

  氢溴酸特力利汀的制备方法

  摘要：

  本发明提供了一种氢溴酸特力利汀的制备方法，其包括如下步骤：制备L‑羟基脯氨酸；将L‑羟基脯氨酸与碳酸氢钠混合后溶于水，加入丙酮，然后滴入二碳酸二叔丁酯室温反应过夜，经后处理得到叔丁氧羰基‑N‑羟脯氨酸；用叔丁氧羰基‑N‑羟脯氨酸制备叔丁氧羰基‑N‑4‑氧代‑脯氨酸；用叔丁氧羰基‑N‑4‑氧代‑脯氨酸制备(2S)‑4‑氧代‑2‑(3‑噻唑烷基羰基)‑1‑吡咯烷羧酸叔丁酯；用化合物IV制备化合物III；用化合物III制备化合物II；用化合物II制备化合物1‑(3‑甲基‑1‑苯基‑1H‑吡唑‑5‑基))哌嗪；制备中间体I；用中间体I制备氢溴酸特力利汀。本发明具有如下的有益效果：1、本发明的制备方法成本较低，仅仅为现有技术中成本的三分之二；2、产率高于95％，纯度高于98％。

  公开号：

  CN106349237A
• 作为产物：
  描述：

  L-羟基脯氨酸 在 氯化亚砜 、 水 、 三乙胺 、 三苯基膦 、 偶氮二甲酸二乙酯 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 18.0h， 生成 N-Boc-顺式-4-羟基-L-脯氨酸
  参考文献：
  名称：

  基于2-甲基-卤代羟脯氨酸的二肽的吡咯烷环起皱和脯氨酰胺键构型。

  摘要：

  使用衍生自d / l丙氨酸的双环内酯的直接氨解方法，开发了一种快速的方法，用于合成含有l-丙氨酸和d / l 2-甲基异羟丙基脯氨酸的同型和杂手性二肽。通过溶液NMR研究确定了C-2甲基化及其空间取向对吡咯烷环折叠和脯氨酰胺键构型的影响。本研究表明，C-2甲基化会导致脯氨酰胺键仅在反式几何结构中均存在于同手性和杂手性二肽中。但是，C-2甲基的空间取向及其在适当加帽的模型二肽中的i + 2位置可能成核为匝状结构。

  DOI：

  10.1039/c9ob00150f

文献信息

• [EN] DERIVATIVES OF 1-[(CYCLOPENTYL OR 2-PYRROLIDINYL)CARBONYLAMINOMETHYL]-4-(1,3-THIAZOL-5-YL) BENZENE WHICH ARE USEFUL FOR THE TREATMENT OF PROLIFERATIVE, AUTOIMMUNE OR INFLAMMATORY DISEASES<br/>[FR] DÉRIVÉS DE 1-[(CYCLOPENTYL OU 2-PYRROLIDINYL)CARBONYLAMINOMÉTHYL]-4-(1,3-THIAZOL-5-YL)-BENZÈNE QUI SONT UTILES POUR LE TRAITEMENT DE MALADIES PROLIFÉRATIVES, AUTO-IMMUNES OU INFLAMMATOIRES
  申请人：UNIV DUNDEE

  公开号：WO2016146985A1

  公开（公告）日：2016-09-22

  There is provided novel small molecule E3 ubiquitin ligase protein binding ligand compounds, having utility in PROteolysis Targeted Chimeras (PROTACs), as well as processes for the preparation thereof, and use in medicine. There is particularly provided PROTACs which bind to a protein within the bromo- and Extra-terminal (BET) family of proteins, and especially to PROTACs including novel small molecule E3 ubiquitin ligase protein binding ligand compounds which selectively induce degradation of the BRD4 protein within the bromodomain of the BET family of proteins.

  提供了新型小分子E3泛素连接酶蛋白结合配体化合物，适用于蛋白质降解靶向嵌合物（PROTACs），以及其制备过程和在医学中的用途。特别提供了能够结合到溴-和额外末端（BET）蛋白家族中的蛋白质的PROTACs，尤其是包括新型小分子E3泛素连接酶蛋白结合配体化合物的PROTACs，其选择性诱导BET蛋白家族中溴结构域内的BRD4蛋白降解。
• [EN] NEW PYRROLIDINE-2-CARBOXYLIC ACID DERIVATIVES FOR TREATING PAIN AND PAIN RELATED CONDITIONS<br/>[FR] NOUVEAUX DÉRIVÉS D'ACIDE PYRROLIDINE-2-CARBOXYLIQUE POUR LE TRAITEMENT DE LA DOULEUR ET D'ÉTATS PATHOLOGIQUES ASSOCIÉS À LA DOULEUR
  申请人：ESTEVE PHARMACEUTICALS SA

  公开号：WO2020120539A1

  公开（公告）日：2020-06-18

  The present invention relates to new compounds that show pharmacological dual activity towards the subunit α2δ of voltage-gated calcium channels (VGCC), especially the α2δ-1 subunit of voltage-gated calcium channels, and the µ-opiod receptor (MOR or mu-opioid). The invention is also related to the process for the preparation of said compounds as well as to compositions comprising them, and to their use as medicaments (formula (I)).

  本发明涉及显示对电压门控钙通道（VGCC）的α2δ亚基，特别是电压门控钙通道的α2δ-1亚基，以及µ-阿片受体（MOR或μ-阿片）具有药理双重活性的新化合物。该发明还涉及所述化合物的制备过程，以及包含它们的组合物，以及它们作为药物的用途（公式（I））。
• 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。
• SUBSTITUTED PYRROLIDINE AMIDES AS MODULATORS OF THE HISTAMINE H3 RECEPTOR
  申请人：Carruthers Nicholas I.

  公开号：US20090291903A1

  公开（公告）日：2009-11-26

  Certain substituted pyrrolidine amide compounds are histamine H 3 receptor modulators useful in the treatment of histamine H 3 receptor-mediated diseases.

  某些替代吡咯烷酰胺化合物是组胺H3受体调节剂，可用于治疗组胺H3受体介导的疾病。
• [EN] SULFONAMIDE COMPOUNDS HAVING TNAP INHIBITORY ACTIVITY<br/>[FR] COMPOSÉS DE SULFONAMIDE AYANT UNE ACTIVITÉ INHIBITRICE DE TNAP
  申请人：DAIICHI SANKYO CO LTD

  公开号：WO2018119444A1

  公开（公告）日：2018-06-28

  The present invention relates to a compound or a pharmacologically acceptable salt thereof having excellent tissue non-specific alkaline phosphatase inhibitory activity. The present invention provides a compound represented by the formula (I) or a pharmacologically acceptable salt thereof.

  本发明涉及一种具有优异的组织非特异性碱性磷酸酶抑制活性的化合物或其药理学上可接受的盐。本发明提供一种由式(I)表示的化合物或其药理学上可接受的盐。