顺式-3-羟基-L-脯氨酸 | 567-35-1

• 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: 顺式-3-羟基-L-脯氨酸
• 中文别名: (2S,3r)-3-羟基吡咯烷-2-羧酸
• 英文名称: (2S,3R)-3-hydroxyproline
• 英文别名: cis-3-hydroxy-L-proline；(2S,3R)-3-hydroxypyrrolidine-2-carboxylic acid
• CAS: 567-35-1
• 化学式: C₅H₉NO₃
• 分子量: 131.131
• InChiKey: BJBUEDPLEOHJGE-DMTCNVIQSA-N

物化性质

• 熔点：
  221-228℃ (dec.) (ethanol water )
• 沸点：
  355.2±42.0 °C(Predicted)
• 密度：
  1.395±0.06 g/cm3 (20 ºC 760 Torr)
• 溶解度：
  酸性DMSO（少量溶解）、DMSO（少量溶解）、水（少量溶解）

计算性质

• 辛醇/水分配系数(LogP)：
  -2.5
• 重原子数：
  9
• 可旋转键数：
  0
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.8
• 拓扑面积：
  77
• 氢给体数：
  2
• 氢受体数：
  3

安全信息

• 储存条件：
  应存放在2-8°C的环境中，避免光照，并保存在惰性气体中。

SDS

Material Safety Data Sheet

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Section 1. Identification of the substance
Product Name: Cis-L-3-hydroxyproline
Synonyms: 3-Hydroxy-(3R)-L-proline

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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: Cis-L-3-hydroxyproline
CAS number: 567-35-1

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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.
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: C5H9NO3
Molecular weight: 131.1

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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：

  顺式-3-羟基-L-脯氨酸 在 cis-3-hydroxy‑L‑proline dehydratase 、 magnesium chloride 作用下， 以 aq. phosphate buffer 、 水 为溶剂， 反应 3.0h， 生成 L-1-pyrroline-5-carboxylic acid
  参考文献：
  名称：

  A Unique cis-3-Hydroxy-l-proline Dehydratase in the Enolase Superfamily

  摘要：

  The genome of Labrenzia aggregata IAM 12614 encodes an uncharacterized member of the muconate lactonizing enzyme (MLE) subgroup of the enolase superfamily (UniProt ID A0NXQ8). The gene encoding A0NXQ8 is located between genes that encode members of the proline racemase superfamily, 4R-hydroxyproline 2-epimerase (UniProt ID A0NXQ7; 4HypE) and trans-3-hydroxy-l-proline dehydratase (UniProt ID A0NXQ9; t3LHypD). A0NXQ8 was screened with a library of proline analogues; two reactions were observed with cis-3-hydroxy-l-proline (c3LHyp), competing 2-epimerization to trans-3-hydroxy-d-proline (1,1-proton transfer) and dehydration to Delta(1)-pyrroline-2-carboxylate (beta-elimination; c3LHyp dehydratase), with eventual total dehydration. The genome context encoding A0NXQ8 both (1) confirms its novel c3LHyp dehydratase function and (2) provides evidence for metabolic pathways that allow L. aggregata to utilize several isomeric 3- and 4-hydroxyprolines as sole carbon sources.

  DOI：

  10.1021/ja5103986
• 作为产物：
  描述：

  L-脯氨酸 在 iron(II) sulfate 、 disodium α-ketoglutarate 作用下， 以 culture medium 为溶剂， 反应 72.0h， 以61%的产率得到顺式-3-羟基-L-脯氨酸
  参考文献：
  名称：

  用重组表达的脯氨酸羟化酶对L-脯氨酸和L-哌柯酸进行选择性羟化的简单程序

  摘要：

  由于脯氨酸羟化酶具有不同的区域选择性和立体选择性，因此可以直接获得羟脯氨酸和其他羟基化的环式氨基酸，这是化学合成的重要手性基石，而经典化学合成通常无法以合理的费用获得。迄今为止，脯氨酸羟化酶的应用仅限于生产两种羟脯氨酸异构体的复杂工业方法。这主要是由于其异源表达困难，体外稳定性有限以及复杂的产品纯化程序所致。在这里，我们描述了一种简便的生产顺式‐3‐，顺式‐4‐和反式的方法-4-脯氨酸羟化酶，以及它们用于的区域选择性和立体选择性的羟基化应用大号脯氨酸和其六元环同源物1-哌可酸。由于在体外催化用这些酶不是非常有效和转换被限制在毫克规模，一个在体内过程成立，这允许6 mM的定量转化1-脯氨酸在摇瓶培养。通过离子交换色谱纯化简便的产品后，羟脯氨酸的分离率为35-61％（每瓶175-305 mg）。大号-用分离出的酶将哌可可酸转化，以证明反应的选择性。在优化铁（II）浓度的转化中，实现了17-68

  DOI：

  10.1002/adsc.201000863
• 作为试剂：
  描述：

  对硝基苯甲醛 、 丙酮 在 顺式-3-羟基-L-脯氨酸 作用下， 以 二甲基亚砜 为溶剂， 反应 18.0h， 生成 (4R)-4-hydroxy-4-(4-nitrophenyl)-butan-2-one 、 (4S)-4-hydroxy-4-(4-nitrophenyl)-butan-2-one
  参考文献：
  名称：

  羟基-L-脯氨酸作为羟醛、迈克尔加成和曼尼希反应的不对称催化剂

  摘要：

  羟脯氨酸 (Hyps) 2-6 被测试为羟醛、迈克尔加成和曼尼希反应的有机催化剂。结果与众所周知的类似物L-脯氨酸(1)进行了比较。研究了额外羟基和手性中心在三种反应中的影响。催化剂 2 显示出醛醇反应立体选择性的增强，而迈克尔加成中的 3 和曼尼希反应中的 5 给出了最好的结果。羟脯氨酸的衍生物在催化行为方面表现出多样性，如 6。

  DOI：

  10.3998/ark.5550190.0013.609

文献信息

• Regio- and stereoselective oxygenation of proline derivatives by using microbial 2-oxoglutarate-dependent dioxygenases
  作者：Ryotaro Hara、Naoko Uchiumi、Naoko Okamoto、Kuniki Kino

  DOI：10.1080/09168451.2014.918490

  日期：2014.8.3

  We evaluated the substrate specificities of four proline cis-selective hydroxylases toward the efficient synthesis of proline derivatives. In an initial evaluation, 15 proline-related compounds were investigated as substrates. In addition to l-proline and l-pipecolinic acid, we found that 3,4-dehydro-l-proline, l-azetidine-2-carboxylic acid, cis-3-hydroxy-l-proline, and l-thioproline were also oxygenated. Subsequently, the product structures were determined, revealing cis-3,4-epoxy-l-proline, cis-3-hydroxy-l-azetidine-2-carboxylic acid, and 2,3-cis-3,4-cis-3,4-dihydroxy-l-proline.

  我们评估了四种脯氨酸顺式选择性羟化酶对脯氨酸衍生物高效合成的底物特异性。在初步评估中，我们研究了15种脯氨酸相关化合物作为底物。除了l-脯氨酸和l-哌哌酸外，我们发现3,4-去氢脯氨酸、l-吡啶二羧酸、顺式-3-羟基-l-脯氨酸和l-硫脯氨酸也被氧化。随后，确定了产物结构，揭示了顺式-3,4-环氧-l-脯氨酸、顺式-3-羟基-l-吡啶二羧酸和2,3-顺式-3,4-顺式-3,4-二羟基-l-脯氨酸。
• Studies on the selectivity of proline hydroxylases reveal new substrates including bicycles
  作者：Tristan J. Smart、Refaat B. Hamed、Timothy D.W. Claridge、Christopher J. Schofield

  DOI：10.1016/j.bioorg.2019.103386

  日期：2020.1

  Studies on the substrate selectivity of recombinant ferrous-iron- and 2-oxoglutarate-dependent proline hydroxylases (PHs) reveal that they can catalyse the production of dihydroxylated 5-, 6-, and 7-membered ring products, and can accept bicyclic substrates. Ring-substituted substrate analogues (such hydroxylated and fluorinated prolines) are accepted in some cases. The results highlight the considerable

  对依赖于铁-铁和2-氧戊二酸酯的脯氨酸羟化酶重组酶的底物选择性的研究表明，它们可以催化二羟基化的5、6和7元环产物的产生，并且可以接受双环底物。在某些情况下，可以接受环取代的底物类似物（例如羟基化和氟化的脯氨酸）。结果突出了在生物催化中氨基酸羟化酶和其他2OG加氧酶的巨大潜力，但尚未充分开发。
• Modular Chemoenzymatic Synthesis of GE81112 B1 and Related Analogues Enables Elucidation of Its Key Pharmacophores
  作者：Christian R. Zwick、Max B. Sosa、Hans Renata

  DOI：10.1021/jacs.0c13424

  日期：2021.1.27

  initiation. Herein we report the use of a chemoenzymatic strategy to complete the first total synthesis of GE81112 B1. By pairing iron and α-ketoglutarate dependent hydroxylases found in GE81112 biosynthesis with traditional synthetic methodology, we were able to access the natural product in 11 steps (longest linear sequence). Following this strategy, 10 GE81112 B1 analogues were synthesized, allowing for identification

  GE81112 复合物因其广泛的抗菌特性和独特的抑制细菌翻译起始的能力而备受关注。在此，我们报告了使用化学酶促策略完成 GE81112 B1 的首次全合成。通过将 GE81112 生物合成中发现的铁和 α-酮戊二酸依赖性羟化酶与传统合成方法配对，我们能够通过 11 个步骤（最长的线性序列）获得天然产物。遵循这一策略，合成了 10 个 GE81112 B1 类似物，从而确定了其关键药效团。我们药物化学工作的一个关键特征是在模块化类似物合成中加入额外的生物催化羟基化，以快速探索相关的化学空间。
• Asymmetric Syntheses of All Stereoisomers of 3-Hydroxyproline; A Constituent of Several Bioactive Compounds
  作者：Srivari Chandrasekhar、Togapur Kumar

  DOI：10.1055/s-0032-1316734

  日期：——

  3-hydroxyproline, and its derivatives have been achieved enantioselectively by employing Sharpless asymmetric epoxidation and reductive cyclization as the key steps. Synthesis of an unusual β-hydroxy-α-amino acid, 3-hydroxyproline, and its derivatives have been achieved enantioselectively by employing Sharpless asymmetric epoxidation and reductive cyclization as the key steps.

  摘要 通过使用Sharpless不对称环氧化和还原环化作为关键步骤，对映体选择性合成了一种不寻常的β-羟基-α-氨基酸，3-羟基脯氨酸及其衍生物。 通过使用Sharpless不对称环氧化和还原环化作为关键步骤，对映体选择性合成了一种不寻常的β-羟基-α-氨基酸，3-羟基脯氨酸及其衍生物。
• Total Synthesis of Cyclothialidine
  作者：Erwin Götschi、Christian-Johannes Jenny、Peter Reindl、Fabienne Ricklin

  DOI：10.1002/hlca.19960790816

  日期：1996.12.11

  ester derivative 25 thereof and its subsequent coupling with Boc-Ser-Cys-OMe (11); cyclization of the ω-hydroxy acid 2929 to the 12-membered lactone 30 using preferably Mitsunobu conditions; completion of the peptidic side chains of 1 using Boc strategy (Scheme 4). Optically pure cis-N-(tert-butoxycarbonyl)-3-hydroxy-L-proline ((–)-14) was obtained by resolution of the racemate via an efficient reaction

  描述了从硫链霉菌分离出的一种新的DNA促旋酶抑制剂cyclothialidine（1）的总合成。通过制备内酯13（方案2）来测试合成的概念，该内酯13包含特征性双环核心实体1。合成1的关键特征是：通过两个连续的曼尼希氨基甲基化/氢化序列，由3,5-二羟基苯甲酸（19）制备3,5-二羟基-2,6-二甲基苯甲酸（23）；酯衍生物的苄基N-溴琥珀酰亚胺溴化25其及其随后与Boc-Ser-Cys-OMe的偶联（11）；使用优选的Mitsunobu条件将ω-羟基酸29 29环化为12元内酯30；的肽侧链的完成1使用Boc策略（路线4）。通过外消旋物通过含有脂肪酶催化的对映体特异性乙酸酯水解的有效反应序列拆分，得到旋光纯的顺式-N-（叔丁氧基羰基）-3-羟基-L-脯氨酸（（-）- 14）（方案3） 。自然结构1通过与合成材料比较确认。描述的合成路线还提供方便的类似物1，例如经由中间30。