Cbz-反式-4-羟基-L-脯氨醇 | 73872-71-6

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 谷氨酸类衍生物
• 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: Cbz-反式-4-羟基-L-脯氨醇
• 中文别名: BOC-D-谷氨酸1叔丁酯；N-BOC-D-谷氨酸1-叔丁酯
• 英文名称: boc-D-glutamic acid α-tert-butyl ester
• 英文别名: (R)-5-(tert-butoxy)-4-((tert-butoxycarbonyl)amino)-5-oxopentanoic acid；Boc-D-Glu-OtBu；(4R)-5-[(2-methylpropan-2-yl)oxy]-4-[(2-methylpropan-2-yl)oxycarbonylamino]-5-oxopentanoic acid
• CAS: 73872-71-6
• 化学式: C₁₄H₂₅NO₆
• mdl: MFCD00076926
• 分子量: 303.356
• InChiKey: YMOYURYWGUWMFM-SECBINFHSA-N

物化性质

• 沸点：
  449.8±40.0 °C(Predicted)
• 密度：
  1.121

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  21
• 可旋转键数：
  9
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.785
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  6

安全信息

• 海关编码：
  2924199090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335

SDS

Material Safety Data Sheet

---

Section 1. Identification of the substance
Product Name: Boc-d-glu-otbu
Synonyms:

---

Section 2. Hazards identification
Harmful by inhalation, in contact with skin, and if swallowed.

---

Section 3. Composition/information on ingredients.
Ingredient name: Boc-d-glu-otbu
CAS number: 73872-71-6

---

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.

---

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.

---

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.

---

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:

---

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.

---

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: C14H25NO6
Molecular weight: 303.4

---

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.

---

Section 11. Toxicological information
No data.

---

Section 12. Ecological information
No data.

---

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.

---

Section 14. Transportation information
Non-harzardous for air and ground transportation.

---

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.

---

SECTION 16 - ADDITIONAL INFORMATION
N/A

反应信息

• 作为反应物：
  描述：

  Cbz-反式-4-羟基-L-脯氨醇 在 N-甲基吗啉 、 咪唑 、 碘 、 三苯基膦 、 氯甲酸异丁酯 作用下， 以 四氢呋喃 为溶剂， 反应 14.5h， 生成 tert-butyl (R)-2-((tert-butoxycarbonyl)amino)-5-iodopentanoate
  参考文献：
  名称：

  [EN] MLL1 INHIBITORS AND ANTI-CANCER AGENTS
  [FR] INHIBITEURS DE MLL1 ET AGENTS ANTICANCÉREUX

  摘要：

  本发明提供了一种公式（I）的化合物：或其对映体、对映体混合物或药学上可接受的盐；其中变量如本文所定义。本发明还提供了包含这样的化合物的药物组合物；以及使用这样的化合物治疗由混合谱系白血病1（MLL1）介导的疾病或病况的方法。

  公开号：

  WO2021239077A1
• 作为产物：
  描述：

  Boc-D-Glu(α-O^tBu)(γ-OBn) 在 palladium 10% on activated carbon 、 氢气 作用下， 以 乙醇 为溶剂， 20.0 ℃ 、310.27 kPa 条件下， 反应 3.0h， 生成 Cbz-反式-4-羟基-L-脯氨醇
  参考文献：
  名称：

  C类β-内酰胺酶的新型共价抑制剂揭示了扩展的活性位点特异性

  摘要：

  先前已经证明，O-芳氧基羰基异羟肟酸酯通过使活性位点中的丝氨酸和赖氨酸残基交联而有效地灭活C类β-内酰胺酶。这些抑制剂的新类似物，d - （[R ）- Ö - （苯氧基羰基） - ñ - [（4-氨基-4-羧基-1-丁基）氧基羰基]羟胺，设计成灭活某些低分子量DD -peptidases ，现已合成。尽管发现新分子只是后者酶的弱灭活剂，但出乎意料的是，它被证明是一种非常有效的灭活剂（k i = 3.5×10 4 M –1 s –1）C类β-内酰胺酶，比原始的先导化合物O-苯氧羰基-N-（苄氧羰基）羟胺更是如此。此外，灭活的机制是不同的。质谱表明，新分子使β-内酰胺酶失活涉及形成O-烷氧基羰基异羟肟酸酯与亲核活性位点丝氨酸残基。该酰基酶不像前导化合物那样环化以交联活性位点。模型的建立表明，由于新分子的侧链极性末端与与活性位点邻接的Ω环的元素（尤其是Arg 204）之间的良好相互作用，因此可能

  DOI：

  10.1021/acs.biochem.5b01149

文献信息

• Composition Containing Novel Glutamic Acid Derivative And Block Copolymer, And Use Thereof
  申请人：Nippon Kayaku Kabushiki Kaisha

  公开号：US20200190101A1

  公开（公告）日：2020-06-18

  Provided is a pharmaceutical preparation that is suitable for more effectively exhibiting the efficacy of a glutamic acid derivative, which is a GGT-recognizable prodrug, by producing a composition including a glutamic acid derivative capable of rapidly releasing a physiologically active substance by being recognized by GGT, or a pharmacologically acceptable salt thereof; and a block copolymer in which a polyethylene glycol segment is linked to a polyamino acid segment with a hydrophobic group. Particularly, the composition based on a glutamic acid derivative that uses an antitumor compound as a physiologically active substance is capable of effectively accumulating the glutamic acid derivative at a tumor affected area, exhibits a superior effect against tumors, and is capable of suppressing the release of a physiologically active substance in bone marrow tissue where the expression ratio of GGT is low. Therefore, side effects such as myelosuppression, which pose a problem in the use of antitumor drugs, may be avoided.

  提供的是一种药物制剂，适用于更有效地展现谷氨酸衍生物的功效，该衍生物是一种GGT可识别的前药，通过制备包括一种能够被GGT识别从而快速释放生理活性物质的谷氨酸衍生物或其药理学可接受的盐的组合物；以及一种嵌段共聚物，其中聚乙二醇段与一个疏水基团连接到一个聚氨基酸段。特别是，基于谷氨酸衍生物的组合物使用抗肿瘤化合物作为生理活性物质，能够有效地在受肿瘤影响的区域积累谷氨酸衍生物，对肿瘤具有优越效果，并能够抑制在GGT表达比例较低的骨髓组织中释放生理活性物质。因此，可以避免使用抗肿瘤药物时可能出现的骨髓抑制等副作用。
• [EN] NEW DERIVATIVES OF INDOLE FOR THE TREATMENT OF CANCER, VIRAL INFECTIONS AND LUNG DISEASES<br/>[FR] NOUVEAUX DÉRIVÉS D'INDOLE UTILES DANS LE TRAITEMENT DU CANCER, DES INFECTIONS VIRALES ET DES MALADIES PULMONAIRES
  申请人：BIOKINESIS

  公开号：WO2014086964A1

  公开（公告）日：2014-06-12

  The present invention relates to a new class of indole derivatives, having a particular MKlp2 inhibition profile and useful as a therapeutic agent, in particular for the treatment of cancer, viral infections and lung diseases.

  本发明涉及一类新的吲哚衍生物，具有特定的MKlp2抑制剂作用，并可用作治疗剂，特别是用于癌症、病毒感染和肺部疾病的治疗。
• Design, Synthesis, and Biological Evaluation of Beauveriolide Analogues Bearing Photoreactive Amino Acids
  作者：Yuichi Masuda、Kazumasa Aoyama、Masahito Yoshida、Keisuke Kobayashi、Taichi Ohshiro、Hiroshi Tomoda、Takayuki Doi

  DOI：10.1248/cpb.c16-00095

  日期：——

  we designed beauveriolide analogues 1a-1d wherein the Leu or D-allo-Ile residue was replaced by photoreactive amino acids possessing methyldiazirine or trifluoromethyldiazirine in the side chains. The methyldiazirine moiety was installed by reaction of methyl ketones with liquid ammonia to provide imine intermediates, followed by treatment with hydroxylamine-O-sulfonic acid to provide the diaziridines

  据报道，天然存在的环二肽中的白僵菌内酯I和III与固醇O-酰基转移酶（SOAT）结合，抑制了其合成胆固醇酯的能力。为便于分析这些化合物的结合位点，我们设计了甜菜素内酯类似物1a-1d，其中Leu或D-allo-Ile残基被侧链上具有甲基二氮杂或三氟甲基二氮杂的光敏氨基酸取代。通过使甲基酮与液氨反应以提供亚胺中间体来安装甲基二嗪基部分，然后用羟胺-O-磺酸处理以提供二氮丙啶。随后的氧化得到甲基二嗪。相反，三氟甲基二嗪衍生物是通过肟中间体由三氟甲基酮制备的，将其转化为重氮丙啶。随后的氧化得到三氟甲基重氮。将合成的光反应性氨基酸3a-3d与3-羟基-4-甲基辛酸4和二肽5偶联，然后进行大内酰胺化，以提供甜菜碱内酯类似物1a-1d。发现1a-1d的SOAT抑制活性与金紫红色内酯I和III一样有效。此外，1a-1d选择性抑制SOAT1而不是SOAT2，这也与金紫苏内酯I和III的行为一致。发现1a-
• [EN] NOVEL COMPOUNDS AND COMPOSITION FOR TARGETED THERAPY OF KIDNEY-ASSOCIATED CANCERS<br/>[FR] NOUVEAUX COMPOSÉS ET COMPOSITION POUR LA THÉRAPIE CIBLÉE DE CANCERS ASSOCIÉS AU REIN
  申请人：MICURX PHARMACEUTICALS INC

  公开号：WO2021150792A1

  公开（公告）日：2021-07-29

  The present invention provides therapeutic compounds of the following formula I: or pharmaceutically acceptable salts, hydrates, or solvates thereof that are therapeutic or anticancer agents, pharmaceutical compositions containing them, methods for their use, and methods for preparing these compounds.

  本发明提供了以下化合物I的治疗性化合物：或其药用可接受的盐、水合物或溶剂合物，这些化合物是治疗性或抗癌剂，包含它们的药物组合物，使用它们的方法，以及制备这些化合物的方法。
• ENZYME AND RECEPTOR MODULATION
  申请人：Davidson Alan Hornsby

  公开号：US20100317865A1

  公开（公告）日：2010-12-16

  Covalent conjugates of an α,α-disubstituted glycine ester and a modulator of the activity of a target intracellular enzyme or receptor, wherein the ester group of the conjugate is hydrolysable by one or more intracellular carboxylesterase enzymes to the corresponding acid and the α,α-disubstituted glycine ester is conjugated to the modulator at a position remote from the binding interface between the inhibitor and the target enzyme or receptor pass into cells and the active acid hydrolysis product accumulates within the cells.

  一种α，α-二取代甘氨酸酯和靶细胞内酶或受体活性调节剂的共价结合物，其中共轭物的酯基可被一个或多个细胞内羧酯酶水解为相应的酸，α，α-二取代甘氨酸酯与调节剂结合在远离抑制剂与靶酶或受体之间结合界面的位置，进入细胞并使活性酸水解产物在细胞内积累。