骆驼蓬碱 | 6159-55-3

• 物质功能分类: 生物化工 - 中草药成分
• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 中文名称: 骆驼蓬碱
• 中文别名: 哈尔明；鸭嘴花碱；(R)-1,2,3,9-四氢吡咯并[2,1-B]喹唑啉-3-醇
• 英文名称: (+)-vasicinol
• 英文别名: (-)-peganine；(-)-vasicine；(S)-vasicine；L-vasicine；linarine；peganine；(3S)-1,2,3,9-tetrahydropyrrolo[2,1-b]quinazolin-3-ol
• CAS: 6159-55-3
• 化学式: C₁₁H₁₂N₂O
• mdl: MFCD01544498
• 分子量: 188.229
• InChiKey: YIICVSCAKJMMDJ-JTQLQIEISA-N

物化性质

• 熔点：
  211.5°C
• 沸点：
  323.23°C (rough estimate)
• 密度：
  1.1124 (rough estimate)
• 溶解度：
  DMSO：83.33 mg/mL（442.70 mM；需要超声波）

计算性质

• 辛醇/水分配系数(LogP)：
  0.4
• 重原子数：
  14
• 可旋转键数：
  0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  35.8
• 氢给体数：
  1
• 氢受体数：
  2

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 危险类别码：
  R22
• 危险品运输编号：
  UN 1544
• 海关编码：
  2933990090
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 储存条件：
  存储条件：2-8℃，干燥，密闭

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Vasicine
REACH No. : A registration number is not available for this substance as the substance
or its uses are exempted from registration, the annual tonnage does not
require a registration or the registration is envisaged for a later
registration deadline.
CAS-No. : 6159-55-3
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
Classification according to Regulation (EC) No 1272/2008
Acute toxicity, Oral (Category 4), H302
For the full text of the H-Statements mentioned in this Section, see Section 16.
Classification according to EU Directives 67/548/EEC or 1999/45/EC
Xn Harmful R22
For the full text of the R-phrases mentioned in this Section, see Section 16.
Label elements
Labelling according Regulation (EC) No 1272/2008
Pictogram
Signal word Warning
Hazard statement(s)
H302 Harmful if swallowed.
Precautionary statement(s) none
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Formula : C11H12N2O
Molecular Weight : 188,23 g/mol
CAS-No. : 6159-55-3
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Vasicine
CAS-No. 6159-55-3 Acute Tox. 4; H302 <= 100 %
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Vasicine
CAS-No. 6159-55-3 Xn, R22 <= 100 %
For the full text of the H-Statements and R-Phrases mentioned in this Section, see Section 16

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SECTION 4: First aid measures
Description of first aid measures
General advice
Consult a physician. Show this safety data sheet to the doctor in attendance.
If inhaled
If breathed in, move person into fresh air. If not breathing, give artificial respiration. Consult a physician.
In case of skin contact
Wash off with soap and plenty of water. Consult a physician.
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. Consult a physician.
Most important symptoms and effects, both acute and delayed
The most important known symptoms and effects are described in the labelling (see section 2.2) and/or in
section 11
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
Use personal protective equipment. Avoid dust formation. Avoid breathing vapours, mist or gas. Ensure
adequate ventilation. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Do not let product enter drains.
Methods and materials for containment and cleaning up
Pick up and arrange disposal without creating dust. Sweep up and shovel. 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
Avoid contact with skin and eyes. Avoid formation of dust and aerosols.
Provide appropriate exhaust ventilation at places where dust is formed.
For precautions see section 2.2.
Conditions for safe storage, including any incompatibilities
Store in cool place. Keep container tightly closed in a dry and well-ventilated place.
Specific end use(s)
A part from the uses mentioned in section 1.2 no other specific uses are stipulated

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SECTION 8: Exposure controls/personal protection
Control parameters
Components with workplace control parameters
Exposure controls
Appropriate engineering controls
Handle in accordance with good industrial hygiene and safety practice. Wash hands before breaks and
at the end of workday.
Personal protective equipment
Eye/face protection
Safety glasses with side-shields conforming to EN166 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
Complete suit protecting against chemicals, The type of protective equipment must be selected
according to the concentration and amount of the dangerous substance at the specific workplace.
Respiratory protection
For nuisance exposures use type P95 (US) or type P1 (EU EN 143) particle respirator.For higher
level protection use type OV/AG/P99 (US) or type ABEK-P2 (EU EN 143) respirator cartridges.
Use respirators and components tested and approved under appropriate government standards
such as NIOSH (US) or CEN (EU).
Control of environmental exposure
Do not let product enter drains.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: powder
Colour: off-white
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 no data available
boiling range
g) Flash point no data available
h) Evapouration 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 no data available
n) Water solubility no data available
o) Partition coefficient: n- no data available
octanol/water
p) Auto-ignition 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
Stable under recommended storage conditions.
Possibility of hazardous reactions
no data available
Conditions to avoid
no data available
Incompatible materials
Oxidizing agents
Hazardous decomposition products
Other decomposition products - no data available
In the event of fire: see section 5

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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 sensitisation
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
Additional Information
RTECS: Not available
To the best of our knowledge, the chemical, physical, and toxicological properties have not been
thoroughly investigated.

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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
PBT/vPvB assessment not available as chemical safety assessment not required/not conducted
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. Dissolve or mix the material
with a combustible solvent and burn in a chemical incinerator equipped with an afterburner and scrubber.
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

制备方法与用途

生物活性

Vasicine 是一种分离自骆驼蓬（A. vasica）的生物碱，具有天然的胆碱酯酶抑制作用。在临床前模型中，它表现出抗胆碱酯酶活性，因此被视为阿尔茨海默病治疗药物开发的重要候选物质。

化学性质

Vasicine 是一种白色针状结晶，能够溶于甲醇、乙醇和 DMSO 等有机溶剂。

用途

主要用于含量测定、鉴定以及药理实验等。

反应信息

• 作为反应物：
  描述：

  骆驼蓬碱 在 POCl₃#PCl₅ 作用下， 生成 3-去氧鸭嘴花碱
  参考文献：
  名称：

  天然（−）‐ Vasicine作为光学纯的1-Benzylpyrrolidin‐3‐ol的新型来源

  摘要：

  据报道，一种重要的药物前体光学活性（3 S）-1-苄基吡咯烷酮3-ol（3）的制备方法简便易行。（ - ） -选自天然存在的生物碱开始vasicine（1），一个大工厂的生物碱藏药vasica，3在84％的总收率（获得方案3）。

  DOI：

  10.1002/hlca.201200307
• 作为产物：
  描述：

  (±)-鸭咀花碱 在 D-酒石酸 作用下， 生成 骆驼蓬碱
  参考文献：
  名称：

  Spaeth; Hicks; Zajic, Chemische Berichte, 1935, vol. 68, p. 1389

  摘要：

  DOI：
• 作为试剂：
  描述：

  胡椒醛 、 diethylzinc 在 骆驼蓬碱 作用下， 以 甲苯 为溶剂， 反应 12.5h， 以86%的产率得到
  参考文献：
  名称：

  瓦西辛作为三齿配体，用于将二乙基锌对映体选择性地加成到醛中

  摘要：

  描述了天然1- vasicine作为三齿手性配体用于将二乙基锌对映选择地添加到各种脂族和芳族醛中的第一个报道。所述配体产生仲醇的R-异构体，其高达98％ee。喹唑啉结构可能赋予配体刚性，因此，始终如一的高对映选择性。与其他相关配体的反应（部分缺乏结构特征）也支持了喹唑啉环的重要性，从而导致较差的对映选择性。

  DOI：

  10.1016/j.tetlet.2014.03.002

文献信息

• Exploring Derivatives of Quinazoline Alkaloid <scp>l</scp>-Vasicine as Cap Groups in the Design and Biological Mechanistic Evaluation of Novel Antitumor Histone Deacetylase Inhibitors
  作者：Mudassier Ahmad、Mushtaq A. Aga、Javeed Ahmad Bhat、Brijesh Kumar、Abdul Rouf、Neena Capalash、Mubashir Javeed Mintoo、Ashok Kumar、Priya Mahajan、Dilip Manikrao Mondhe、Amit Nargotra、Parduman Raj Sharma、Mohmmad Afzal Zargar、Ram A. Vishwakarma、Bhahwal Ali Shah、Subhash Chandra Taneja、Abid Hamid

  DOI：10.1021/acs.jmedchem.7b00322

  日期：2017.4.27

  inhibited cancer cell growth and induced cell death by various mechanisms. However, 4a was found to induce cell death independent of ROS generation, and unlike many natural product based HDAC inhibitors, 4a was found to be nontoxic under in vivo conditions. Importantly, we for the first time report the possibility of using a 3-hydroxypyrrolidine cap for the synthesis of HDAC inhibitors with good potency

  1- Vasicine是一种喹唑啉生物碱，具有电子致密环，并且在其结构中具有其他功能。利用基于计算机模拟研究的靶向定向合成（TOS），合成了具有显着对接分数的分子，其中包含1- vasicine的不同衍生物作为帽。有趣的是，发现一个分子，即4a，它含有3-羟基吡咯烷作为帽基和一个六碳长的脂肪族链作为连接基，可以抑制HDAC。图4a显示了对I类HDAC同工型的更多特异性。与癌细胞系相比，还发现4a对正常细胞系的细胞毒性较小。4a通过多种机制抑制癌细胞的生长并诱导细胞死亡。但是，发现4a可以诱导细胞死亡而与ROS的产生无关，并且与许多基于天然产物的HDAC抑制剂不同，发现4a在体内条件下是无毒的。重要的是，我们首次报道了使用3-羟基吡咯烷帽合成具有良好效力的HDAC抑制剂的可能性。
• Synthesis of Ofornine mimics from natural product l-vasicine as anti-hypertensive agents
  作者：Mushtaq A. Aga、Sheikh Rayees、Abdul Rouf、Brijesh Kumar、Anjna Sharma、P.V.V.S. Nagaraju、Gurdarshan Singh、Subhash C. Taneja

  DOI：10.1016/j.bmc.2017.01.006

  日期：2017.2

  report the chemical synthesis of Ofornine mimics from l-vasicine, structure-activity relationship studies and their in vivo screening for anti-hypertensive action in Wistar rats. It was observed that most of the analogs possessed anti-hypertensive effect; however, the duration of the effect was variable and mostly transient. The results demonstrated that the analogs 12, 13, 14, 15, and 16 showed a sharp

  我们报告了L-vasicine的Ofornine模拟物的化学合成，结构-活性关系研究以及它们在Wistar大鼠中的抗高血压作用的体内筛选。据观察，大多数类似物都具有抗高血压作用。但是，效果的持续时间是可变的，并且大多是短暂的。结果表明，类似物12、13、14、15和16在静脉内给药后30-60分钟内收缩压和舒张压急剧而显着降低。类似物（S）-（3-羟基吡咯烷-1-基）（2-（吡啶-4-基氨基）苯基）甲酮（8）以剂量依赖性方式显示血压显着降低，最大反应降至79.29±4.26静脉内剂量为10mg / kg时，SBP为mmHg，DBP为62.55±2.9。此外，显着的抗高血压作用8持续了大约2。10mg / kg剂量5h。我们还根据OECD指南评估了类似物8的急性毒性，发现该化合物在剂量为2000mg / kg体重时是安全的。这些临床前发现表明，类似物8可以被认为是有前途的先导和持久的抗高血压
• Stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic pharmacodynamics, and toxic properties of vasicine enantiomers in vitro and in vivo
  作者：Yudan Zhu、Wei Liu、Shenglan Qi、Hanxue Wang、Yuwen Wang、Gang Deng、Yunpeng Zhang、Shuping Li、Chao Ma、Yongli Wang、Xuemei Cheng、Changhong Wang

  DOI：10.1016/j.ejps.2018.07.058

  日期：2018.10

  Vasicine (VAS) is a potential natural cholinesterase inhibitor for treatment of Alzheimer's disease. Due to one chiral centre (C-3) presenting in molecule, VAS has two enantiomers, d-vasicine (d-VAS) and l-vasicine (l-VAS). The study was undertaken to investigate the stereoselective glucuronidation metabolism, pharmacokinetics, anti-amnesic effect and acute toxicity of VAS enantiomers. In results,

  Vasicine（VAS）是潜在的天然胆碱酯酶抑制剂，可用于治疗阿尔茨海默氏病。由于分子中存在一个手性中心（C-3），VAS具有两种对映异构体，即d-vasicine（d-VAS）和l-vasicine（1-VAS）。进行该研究以研究VAS对映异构体的立体选择性葡萄糖醛酸化代谢，药代动力学，抗健忘作用和急性毒性。结果，在人肝微粒体和同工酶试验中，l-VAS的葡萄糖醛酸化代谢速率比d-VAS快，并且证明UDP-葡萄糖醛酸糖基转移酶（UGT）1A9和UGT2B15是l-VAS葡萄糖醛酸化的主要代谢酶。 VAS，而只有d-VAS的UGT1A9，在HLM和rhUGT1A9中，d-VAS的代谢亲和力明显低于l-VAS。d-VAS在大鼠中的血浆暴露为1.3倍和1。静脉内和口服给予d-VAS和l-VAS后，它们分别比l-VAS高6倍。而且，无论是静脉内还是口服给药，主要葡萄糖醛酸化代谢产物d-VASG的
• PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES
  申请人：Taneja Subhash Chandra

  公开号：US20120101285A1

  公开（公告）日：2012-04-26

  The present invention relates to a facile, highly efficient and economical process for the preparation of optically active N-benzyl-3-hydroxypyrrolidine in high yield from a naturally occurring alkaloid vasicine. The natural alkaloid vasicine is used as a precursor of (S)—N-benzyl-3-hydroxypyrrolidine and (R)—N-benzyl-3-hydroxypyrrolidines which can easily be sourced from the medicinal plant Adatoda vasica by the method known in the art and transformed to optical isomers (R) and (S)—N-benzyl-3-hydroxypyrrolidine by the method described in the present invention.

  本发明涉及一种简便、高效、经济的方法，用于从天然生物碱vasicine中高产得到光学活性的N-苄基-3-羟基吡咯烷。天然生物碱vasicine被用作(S)-N-苄基-3-羟基吡咯烷和(R)-N-苄基-3-羟基吡咯烷的前体，这些可通过已知的方法从药用植物Adatoda vasica中轻易获取，并通过本发明中所述的方法转化为光学异构体(R)和(S)-N-苄基-3-羟基吡咯烷。
• [EN] A PROCESS FOR THE PREPARATION OF OPTICALLY ACTIVE N-BENZYL-3 HYDROXYPYRROLIDINES<br/>[FR] PROCÉDÉ DE PRÉPARATION DE N-BENZYL-3-HYDROXYPYRROLIDINES OPTIQUEMENT ACTIVES
  申请人：COUNCIL SCIENT IND RES

  公开号：WO2010058429A8

  公开（公告）日：2011-07-07