Cbz-反式-4-羟基-L-脯氨醇 | 95687-41-5

• 物质功能分类: 生物化工 - 氨基酸及其衍生物 - 氨基醇类衍生物
• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: Cbz-反式-4-羟基-L-脯氨醇
• 中文别名: CBZ-反式-4-羟基-L-脯氨醇；1-Cbz-反式-4-羟基-l-脯氨醇；CBZ-L-羟脯氨醇；反式-N-苄氧羰基-4-羟基-L-脯氨醇；(2S,4R)-N-CBZ-2-羟甲基-4-氧-吡咯烷；CBZ-反-4-羟基-L-脯氨醇
• 英文名称: (2S,4R)-N1-(benzyloxycarbonyl)-4-hydroxy-2-(hydroxymethyl)-pyrrolidine
• 英文别名: benzyl (2S,4R)-4-hydroxy-2-(hydroxymethyl)pyrrolidine-1-carboxylate
• CAS: 95687-41-5
• 化学式: C₁₃H₁₇NO₄
• 分子量: 251.282
• InChiKey: WDEQGLDWZMIMJM-NWDGAFQWSA-N

物化性质

• 沸点：
  240 °C(lit.)
• 密度：
  1.297 g/mL at 25 °C(lit.)
• 闪点：
  >230 °F
• 稳定性/保质期：

  在常温常压下稳定，应避免接触强氧化剂。

计算性质

• 辛醇/水分配系数(LogP)：
  0.5
• 重原子数：
  18
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  4

安全信息

• 危险等级：
  IRRITANT
• 危险品标志：
  Xi
• WGK Germany：
  3
• 海关编码：
  2933990090
• 危险性防范说明：
  P261,P280,P305+P351+P338
• 危险性描述：
  H302,H315,H319,H332,H335
• 储存条件：
  保持贮藏器密封，并将其放入一个紧密封装的容器中。储存在阴凉、干燥的地方。

SDS

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Section 1. IDENTIFICATION OF THE SUBSTANCE/MIXTURE
Product identifiers
Product name : Z-trans-4-Hydroxy-L-prolinol
CAS-No. : 95687-41-5
Relevant identified uses of the substance or mixture and uses advised against
Identified uses : Laboratory chemicals, Manufacture of substances

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Section 2. HAZARDS IDENTIFICATION
Classification of the substance or mixture
Not a hazardous substance or mixture according to Regulation (EC) No. 1272/2008.
This substance is not classified as dangerous according to Directive 67/548/EEC.
Label elements
Caution - substance not yet tested completely.
Other hazards - none

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Section 3. COMPOSITION/INFORMATION ON INGREDIENTS
Substances
Formula : C13H17NO4
Molecular Weight : 251,28 g/mol

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Section 4. FIRST AID MEASURES
Description of first aid measures
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration.
In case of skin contact
Wash off with soap and plenty of water.
In case of eye contact
Flush eyes with water as a precaution.
If swallowed
Never give anything by mouth to an unconscious person. Rinse mouth with water.
Most important symptoms and effects, both acute and delayed
Indication of any immediate medical attention and special treatment needed
no data available

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Section 5. FIREFIGHTING MEASURES
Extinguishing media
Suitable extinguishing media
Use water spray, alcohol-resistant foam, dry chemical or carbon dioxide.
Special hazards arising from the substance or mixture
Carbon oxides, nitrogen oxides (NOx)
Advice for firefighters
Wear self contained breathing apparatus for fire fighting if necessary.
Further information
no data available

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Section 6. ACCIDENTAL RELEASE MEASURES
Personal precautions, protective equipment and emergency procedures
Avoid breathing vapors, mist or gas.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Keep in suitable, closed containers for disposal.
Reference to other sections
For disposal see section 13.

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Section 7. HANDLING AND STORAGE
Precautions for safe handling
Normal measures for preventive fire protection.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place. Containers which are
opened must be carefully resealed and kept upright to prevent leakage.
Specific end uses
no data available

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Section 8. EXPOSURE CONTROLS/PERSONAL PROTECTION
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
General industrial hygiene practice.
Personal protective equipment
Eye/face protection
Use equipment for eye protection tested and approved under appropriate government standards
such as NIOSH (US) or EN 166(EU).
Skin protection
Handle with gloves. Gloves must be inspected prior to use. Use proper glove removal technique
(without touching glove's outer surface) to avoid skin contact with this product. Dispose of
contaminated gloves after use in accordance with applicable laws and good laboratory practices.
Wash and dry hands.
The selected protective gloves have to satisfy the specifications of EU Directive 89/686/EEC and
the standard EN 374 derived from it.
Body Protection
impervious clothing, The type of protective equipment must be selected according to the
concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
Respiratory protection not required. For nuisance exposures use type OV/AG (US) or type ABEK
(EU EN 14387) respirator cartridges. Use respirators and components tested and approved under
appropriate government standards such as NIOSH (US) or CEN (EU).

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Section 9. PHYSICAL AND CHEMICAL PROPERTIES
Information on basic physical and chemical properties
a) Appearance Form: viscous, liquid
b) Odour no data available
c) Odour Threshold no data available
d) pH no data available
e) Melting point/freezing no data available
point
f) Initial boiling point and 240 °C
boiling range
g) Flash point no data available
h) Evaporation rate no data available
i) Flammability (solid, gas) no data available
j) Upper/lower no data available
flammability or
explosive limits
k) Vapour pressure no data available
l) Vapour density no data available
m) Relative density 1,297 g/mL at 25 °C
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Autoignition no data available
temperature
q) Decomposition no data available
temperature
r) Viscosity no data available
s) Explosive properties no data available
t) Oxidizing properties no data available
Other safety information
no data available

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Section 10. STABILITY AND REACTIVITY
Reactivity
no data available
Chemical stability
no data available
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Strong oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available

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Section 11. TOXICOLOGICAL INFORMATION
Information on toxicological effects
Acute toxicity
no data available
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitization
no data available
Germ cell mutagenicity
no data available
Carcinogenicity
IARC: No component of this product present at levels greater than or equal to 0.1% is identified as
probable, possible or confirmed human carcinogen by IARC.
Reproductive toxicity
no data available
Specific target organ toxicity - single exposure
no data available
Specific target organ toxicity - repeated exposure
no data available
Aspiration hazard
no data available
Potential health effects
Inhalation May be harmful if inhaled. May cause respiratory tract irritation.
Ingestion May be harmful if swallowed.
Skin May be harmful if absorbed through skin. May cause skin irritation.
Eyes May cause eye irritation.
Additional Information
RTECS: Not available

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Section 12. ECOLOGICAL INFORMATION
Toxicity
no data available
Persistence and degradability
no data available
Bioaccumulative potential
no data available
Mobility in soil
no data available
Results of PBT and vPvB assessment
no data available
Other adverse effects
no data available

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Section 13. DISPOSAL CONSIDERATIONS
Waste treatment methods
Product
Offer surplus and non-recyclable solutions to a licensed disposal company.
Contaminated packaging
Dispose of as unused product.

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Section 14. TRANSPORT INFORMATION
UN number
ADR/RID: - IMDG: - IATA: -
UN proper shipping name
ADR/RID: Not dangerous goods
IMDG: Not dangerous goods
IATA: Not dangerous goods
Transport hazard class(es)
ADR/RID: - IMDG: - IATA: -
Packaging group
ADR/RID: - IMDG: - IATA: -
Environmental hazards
ADR/RID: no IMDG Marine pollutant: no IATA: no
Special precautions for user
no data available

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SECTION 15 - REGULATORY INFORMATION
N/A

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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 palladium on activated charcoal 、 镍 吡啶 、 草酰氯 、 potassium tert-butylate 、 氢气 、 氟化氢吡啶 、 一水合肼 、 二甲基亚砜 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醇 、 二氯甲烷 、 水 为溶剂， -55.0~20.0 ℃ 、344.74 kPa 条件下， 反应 35.5h， 生成 1,1'-[(propane-1,3-diyl)dioxy]bis[(11S,11aS)-10-(allyloxycarbonyl)-11-hydroxy-7-methoxy-2-methylidene-1,2,3,10,11,11a-hexahydro-5H-pyrrolo[2,1-c][1,4]benzodiazepin-5-one]
  参考文献：
  名称：

  Linker Length Modulates DNA Cross-Linking Reactivity and Cytotoxic Potency of C8/C8‘ Ether-Linked C2-exo-Unsaturated Pyrrolo[2,1-c][1,4]benzodiazepine (PBD) Dimers

  摘要：

  A C2/C2'-exo-unsaturated pyrrolo [2, 1-c] [1,4]benzodiazepine (PBD) dimer 4b (DRG-16) with a C8-O(CH2)(n)O-C8' diether linkage (n = 5) has been synthesized that shows markedly superior in vitro cytotoxic potency (e.g., > 3400-fold in IGROV1 ovarian cells) and interstrand DNA cross-linking reactivity (> 10-fold) compared to the shorter homologue 4a (SJG-136; n = 3). In contrast, for the C-ring unsubstituted series, the corresponding n = 5 dimer (3c) is generally less cytotoxic and has a lower interstrand cross-linking reactivity compared to its shorter n = 3 homologue (3a). Dimer 4b cross-links DNA with > 10-fold efficiency compared to 4a, and also inhibits the activity of the restriction endonuclease BamH1 more efficiently than either 3a or 4a. The C2-exo-unsaturated PBD dimers 4a,b are not only more effective than their C-ring saturated counterparts in terms of induced DeltaT(m) shift, but they also exert this effect more rapidly. Thus, while 3a and 3c exert 68 and 35% of their maximum effect immediately upon interaction with DNA, this level increases to 76 and 97% for 4a and 4b, respectively. Molecular modeling shows a rank order of 4b (n = 5) > 4a (n = 3) > 3a (n = 3) > 3c (n = 5) in terms of binding energy toward duplexes containing embedded target 5'-GAT(1-2)C cross-link sequences, reflecting the superior fit of the C2-exo-unsaturated rather than saturated C-rings of the PBD dimers. A novel synthesis of core synthetic building blocks for PBD dimers via stepwise Mitsunobu reaction and nitration with Cu(NO3)(2) is also reported.

  DOI：

  10.1021/jm030897l
• 作为产物：
  描述：

  L-羟基脯氨酸 在 sodium tetrahydroborate 、 氯化亚砜 、 水 、 lithium chloride 、 sodium hydroxide 作用下， 以 四氢呋喃 、 甲基叔丁基醚 、 水 为溶剂， 反应 14.5h， 生成 Cbz-反式-4-羟基-L-脯氨醇
  参考文献：
  名称：

  新型杂化分子吡咯并苯二氮卓-蒽羧酰亚胺作为抗体-药物偶联物有效载荷的设计、合成和生物评价

  摘要：

  设计、合成了一系列结合吡咯并苯二氮卓 (PBD) 和蒽羧酰亚胺药效团的新型混合分子，并测试了其对各种癌细胞系的体外细胞毒性。该系列中最有效的化合物37b3表现出亚纳摩尔水平的细胞毒性，IC 50为 0.17–0.94 nM。37b3诱导 DNA 损伤并导致肿瘤细胞周期停滞和细胞凋亡。我们使用37b3作为有效载荷与曲妥珠单抗偶联以获得抗体-药物偶联物 (ADC) T-PBA。T-PBA保持了曲妥珠单抗的靶向模式和内化能力。我们证明了 T-PBA 可以通过溶酶体途径降解以释放有效载荷37b3内化后。T-PBA在体外对 Her2 阳性癌细胞显示出强大的杀伤作用。此外，T-PBA 显着抑制胃癌和卵巢癌异种移植小鼠模型中的肿瘤生长，而没有明显的毒性。总的来说，这些研究表明 T-PBA 代表了一种有前途的新 ADC，值得进一步研究。

  DOI：

  10.1021/acs.jmedchem.2c00471

文献信息

• [EN] CONJUGATED ANTISENSE COMPOUNDS AND THEIR USE<br/>[FR] COMPOSÉS ANTISENS CONJUGUÉS ET LEUR UTILISATION
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2014179620A1

  公开（公告）日：2014-11-06

  Provided herein are oligomeric compounds with conjugate groups. In certain embodiments, the oligomeric compounds are conjugated to N-Acetylgalactosamine.

  本文提供了具有共轭基团的寡聚化合物。在某些实施例中，这些寡聚化合物与N-乙酰半乳糖结合。
• [EN] TARGETED THERAPEUTIC NUCLEOSIDES AND THEIR USE<br/>[FR] NUCLÉOSIDES THÉRAPEUTIQUES CIBLÉES ET LEUR UTILISATION
  申请人：ISIS PHARMACEUTICALS INC

  公开号：WO2015042447A1

  公开（公告）日：2015-03-26

  Provided herein are compounds comprising one or more therapeutic nucleosides and one or more targeting groups. In certain embodiments, the compounds further comprise one or more oligonucleotides. In certain embodiments, a targeting group comprises one or more N-Acetylgalactosamine.

  本文提供的化合物包括一个或多个治疗性核苷和一个或多个靶向基团。在某些实施例中，这些化合物进一步包括一个或多个寡核苷酸。在某些实施例中，一个靶向基团包括一个或多个N-乙酰半乳糖胺。
• NOVEL BENZODIAZEPINE DERIVATIVES AND USES THEREOF
  申请人：IntoCell, Inc.

  公开号：US20190367488A1

  公开（公告）日：2019-12-05

  The present disclosure provides compounds and compositions capable of extending lifespan, and methods of use thereof.

  本公开提供了能够延长寿命的化合物和组合物，以及其使用方法。
• Scale-up Synthesis of Tesirine
  作者：Arnaud C. Tiberghien、Christina von Bulow、Conor Barry、Huajun Ge、Christian Noti、Florence Collet Leiris、Marc McCormick、Philip W. Howard、Jeremy S. Parker

  DOI：10.1021/acs.oprd.8b00205

  日期：2018.9.21

  This work describes the enabling synthesis of tesirine, a pyrrolobenzodiazepine antibody–drug conjugate drug-linker. Over the course of four synthetic campaigns, the discovery route was developed and scaled up to provide a robust manufacturing process. Early intermediates were produced on a kilogram scale and at high purity, without chromatography. Midstage reactions were optimized to minimize impurity

  这项工作描述了能够合成合成的酪胺酸，一种吡咯并苯并二氮杂卓抗体-药物偶联物药物连接物。在四次合成运动过程中，开发了发现路线并扩大了规模，以提供可靠的制造过程。早期中间体以千克规模和高纯度生产，无需色谱。优化了中间阶段的反应，以最大程度地减少杂质的形成。使用少量关键的高压色谱步骤生产和纯化后期材料，最终在34个步骤后得到169 g批料。在撰写本文时，tesirine是多项临床试验中8种抗体-药物偶联物的药物连接物成分，其中4种是关键的。
• Backbone-extended pyrrolidine peptide nucleic acids (bepPNA): design, synthesis and DNA/RNA binding studies
  作者：T. Govindaraju、Vaijayanti A. Kumar

  DOI：10.1039/b413542c

  日期：——

  One-carbon extended conformationally constrained pyrrolidine PNA monomer (bepPNA) has been synthesized, incorporated into PNA sequences at predefined positions, and showed selective RNA binding properties.

  一碳扩展构象约束的吡咯烷PNA单体（bepPNA）已被合成，并在预定位置掺入PNA序列，并显示出选择性的RNA结合特性。