文多灵 | 2182-14-1

• 物质功能分类: 天然产物 - 生物碱
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 鸡蛋花型生物碱
• 中文名称: 文多灵
• 中文别名: 文多林；长春花朵灵；文朵灵
• 英文名称: vindoline
• 英文别名: methyl (1R,9R,10S,11R,12R,19R)-11-acetyloxy-12-ethyl-10-hydroxy-5-methoxy-8-methyl-8,16-diazapentacyclo[10.6.1.01,9.02,7.016,19]nonadeca-2(7),3,5,13-tetraene-10-carboxylate
• CAS: 2182-14-1
• 化学式: C₂₅H₃₂N₂O₆
• 分子量: 456.539
• InChiKey: CXBGOBGJHGGWIE-ACSXSLCXSA-N

物化性质

• 熔点：
  163-1650C
• 比旋光度：
  D20 -18° (chloroform); D27 +42° (chloroform)
• 沸点：
  569.8±50.0 °C(Predicted)
• 密度：
  1.33±0.1 g/cm3(Predicted)
• 溶解度：
  氯仿（微溶）、乙醇（微溶）、甲醇（微溶）
• 稳定性/保质期：

  遵照规定使用和储存，则不会分解。

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  88.5
• 氢给体数：
  1
• 氢受体数：
  8

安全信息

• 危险品标志：
  Xn
• 安全说明：
  S24/25,S36/37
• 危险类别码：
  R68
• 海关编码：
  29339900
• 储存条件：
  存于阴凉干燥处

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Vindoline
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. : 2182-14-1
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
Germ cell mutagenicity (Category 2), H341
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 R68
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)
H341 Suspected of causing genetic defects.
Precautionary statement(s)
P281 Use personal protective equipment as required.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
: Methyl (2β,3β,4β,5α,12R,19α)- 4-(Acetyloxy)-6,7-didehydro-3-hydroxy-
Synonyms
16-methoxy-1-methylaspidospermidine-3-carboxylate
CAS-No. : 2182-14-1
EC-No. : 218-558-0
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Aspidospermidine-3-carboxylic acid, 4-(acetyloxy)-6,7-didehydro-3-hydroxy-16-methoxy-1-methyl-,
methyl ester, (2β,3β,4β,5α,12β,19α)-
CAS-No. 2182-14-1 Muta. 2; H341 <= 100 %
EC-No. 218-558-0
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Aspidospermidine-3-carboxylic acid, 4-(acetyloxy)-6,7-didehydro-3-hydroxy-16-methoxy-1-methyl-,
methyl ester, (2β,3β,4β,5α,12β,19α)-
CAS-No. 2182-14-1 Xn, R68 <= 100 %
EC-No. 218-558-0
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. Evacuate personnel to safe areas. Avoid breathing dust.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. 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.
Store under inert gas.
Specific end use(s)
Apart 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.
Full contact
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Material tested:Dermatril® (KCL 740 / Z677272, Size M)
Splash contact
Material: Nitrile rubber
Minimum layer thickness: 0,11 mm
Break through time: 480 min
Material tested:Dermatril® (KCL 740 / Z677272, Size M)
data source: KCL GmbH, D-36124 Eichenzell, phone [phone], test method: EN374
If used in solution, or mixed with other substances, and under conditions which differ from EN 374,
contact the supplier of the CE approved gloves. This recommendation is advisory only and must
be evaluated by an industrial hygienist and safety officer familiar with the specific situation of
anticipated use by our customers. It should not be construed as offering an approval for any
specific use scenario.
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
Where risk assessment shows air-purifying respirators are appropriate use a full-face particle
respirator type N100 (US) or type P3 (EN 143) respirator cartridges as a backup to engineering
controls. If the respirator is the sole means of protection, use a full-face supplied air respirator. Use
respirators and components tested and approved under appropriate government standards such
as NIOSH (US) or CEN (EU).
Control of environmental exposure
Prevent further leakage or spillage if safe to do so. 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: 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
Strong 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
LDLO Intraperitoneal - mouse - 400 mg/kg
Remarks: Behavioral:Somnolence (general depressed activity). Behavioral:Excitement.
Skin corrosion/irritation
no data available
Serious eye damage/eye irritation
no data available
Respiratory or skin sensitisation
no data available
Germ cell mutagenicity
In vitro tests showed mutagenic effects which were not observed with in vivo test.
Human
Other cell types
Result: positive
Cytogenetic analysis
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: CJ0120000
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
This safety datasheet complies with the requirements of Regulation (EC) No. 1907/2006.
Safety, health and environmental regulations/legislation specific for the substance or mixture
no data available
Chemical Safety Assessment
For this product a chemical safety assessment was not carried out

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SECTION 16: Other information
Full text of H-Statements referred to under sections 2 and 3.
H341 Suspected of causing genetic defects.
Muta. Germ cell mutagenicity
Full text of R-phrases referred to under sections 2 and 3
Xn Harmful
R68 Possible risk of irreversible effects.
Further information
Copyright 2014 Co. LLC. License granted to make unlimited paper copies for internal use
only.
The above information is believed to be correct but does not purport to be all inclusive and shall be
used only as a guide. The information in this document is based on the present state of our knowledge
and is applicable to the product with regard to appropriate safety precautions. It does not represent any
guarantee of the properties of the product. Corporation and its Affiliates shall not be held
liable for any damage resulting from handling or from contact with the above product. See
and/or the reverse side of invoice or packing slip for additional terms and conditions of sale.

制备方法与用途

生物活性

Vindoline 是从长春花（Catharanthus roseus）叶片中提取的一种生物碱，对微管蛋白 (tubulin) 的自组装具有弱抑制作用。

化学性质

Vindoline 可溶于甲醇、乙醇和 DMSO 等有机溶剂，并来源于长春花。

用途

文多灵不仅具有抗菌和消炎的作用，还表现出抗癌活性。作为一种单体长春花碱，它通过抑制微管的组装表现出抗核分裂的活性。

反应信息

• 作为反应物：
  描述：

  文多灵 以70%的产率得到3-demethoxycarbonyl-3-aminomethyl-4-deacetylvindoline
  参考文献：
  名称：

  细胞毒性脱水长春碱酰胺衍生物的合成及其构效关系研究

  摘要：

  设计，合成了一系列3-脱甲氧基羰基-3-酰胺甲基脱水长春碱衍生物（5b - 24b），并评估了它们对两种肿瘤细胞系（A549和HeLa）的增殖抑制活性。大多数酰胺脱水长春碱衍生物表现出强的细胞毒性，所引入的取代基的大小是确定所得细胞毒性活性的最主要因素。针对三种有效化合物（6b，12b和24b）对肉瘤180的体内测试结果表明，在脱水长春碱（1e）的22位引入酰胺基可以提高效力和毒性。

  DOI：

  10.1021/np900157t
• 作为产物：
  描述：

  Ervamycine; 11-甲氧基水甘草碱 在 acetate buffer pH 4.2 、 W-2 Raney Ni 、 苯亚硒酸酐 、 sodium acetate 、 sodium cyanoborohydride 、 potassium carbonate 、 间氯过氧苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 水 、 苯 为溶剂， 生成 文多灵
  参考文献：
  名称：

  快速获取高度氧化的曲霉精生物碱长春花碱，长春花碱和长春花碱

  摘要：

  据报道，通过迄今未知的氮杂二烯（3a，b），一种高度方便有效的合成长春新碱（1a）和长春新碱（1b）的方法。

  DOI：

  10.1039/c39840000909
• 作为试剂：
  描述：

  文多灵 在 文多灵 、 三氟乙酸 、 sodium hydroxide 作用下， 以 乙腈 为溶剂， 反应 25.5h， 生成
  参考文献：
  名称：

  长春多辛及其衍生物的结构与合成

  摘要：

  本文描述了文多啉与甲醛和原甲酸三甲酯反应制备文多碱、三文多碱甲烷和更高分子量的同系物。 10-甲酰基文多灵作为中间体的合成可以进一步探索其化学性质，特别是与丙酮反应产生对称二聚体，该二聚体进一步与文多灵反应得到含有三个和四个文多灵单元的分子。这些分子通过 NMR 进行了表征，其中一些分子（文多碱、10-甲酰基文多啉、10-(1'-(but-1'-en-3'-one))-vindoline）通过 X 射线晶体学进行了表征。根据取代和对称轴的缺失，NMR 谱显示文多灵部分的非等效自旋系统。 10-甲酰文多灵与丙酮双缩合形成的二聚体显示出微摩尔范围内的细胞毒活性。

  DOI：

  10.1002/cbdv.202301928

文献信息

• [EN] A CONJUGATE OF A CYTOTOXIC AGENT TO A CELL BINDING MOLECULE WITH BRANCHED LINKERS<br/>[FR] CONJUGUÉ D'UN AGENT CYTOTOXIQUE À UNE MOLÉCULE DE LIAISON CELLULAIRE AVEC DES LIEURS RAMIFIÉS
  申请人：HANGZHOU DAC BIOTECH CO LTD

  公开号：WO2020257998A1

  公开（公告）日：2020-12-30

  Provided is a conjugation of cytotoxic drug to a cell-binding molecule with a side-chain linker. It provides side-chain linkage methods of making a conjugate of a cytotoxic molecule to a cell-binding ligand, as well as methods of using the conjugate in targeted treatment of cancer, infection and immunological disorders.

  提供了一种将细胞毒性药物与一个侧链连接分子结合的共轭物。它提供了制备细胞毒性分子与细胞结合配体的共轭物的侧链连接方法，以及在靶向治疗癌症、感染和免疫性疾病中使用该共轭物的方法。
• A simple synthesis of bannucine and 5′-epibannucine from (−)-vindoline
  作者：Viktor Ilkei、Péter Bana、Flórián Tóth、Anna Palló、Tamás Holczbauer、Mátyás Czugler、Zsuzsanna Sánta、Miklós Dékány、Áron Szigetvári、László Hazai、Csaba Szántay、Csaba Szántay、György Kalaus

  DOI：10.1016/j.tet.2015.10.020

  日期：2015.12

  is an Aspidosperma alkaloid isolated from the dried leaves of Catharanthus roseus. The molecule is a derivative of vindoline bearing a C10 substituent, a pattern common to the antineoplastic dimeric indole alkaloids of C. roseus. In bannucine, a 2-pyrrolidone moiety is attached at C5′ to the aromatic ring of the vindoline core at C10. In the present work we report the synthesis of bannucine and its

  Bannucine是一种从矢车菊（Catharanthus roseus）的干燥叶片中分离出的一种孢子生物碱。所述分子是文多灵带有C10取代基，图案共同的抗肿瘤二聚吲哚生物碱的衍生物长春花。在bannucine中，将2-吡咯烷酮部分在C5'处连接到在C10上的vindoline核心的芳香环。在目前的工作我们报告bannucine的合成和其来自天然5'-差向异构体（ - ） -文多灵使用环状Ñ -acyliminium离子，其中间体Ñ-酰基氨基甲醇前体是通过琥珀酰亚胺的部分还原而合成的。我们还使用单晶X射线衍射方法描述了两种差向异构体的分离和结构分析，以阐明与C5'碳相连的质子的取向。还研究了纯差向异构体的体外抗肿瘤活性，但两种物质均未在所检查的肿瘤细胞系上显示出显着活性。
• [EN] ULTRA-POTENT VINA ALKALOIDS: ADDED MOLECULAR COMPLEXITY FURTHER DISRUPTS THE TUBLIN DIMER-DIMER INTERFACE<br/>[FR] VINCA-ALCALOÏDES ULTRA-PUISSANTS : PERTURBATION SUPPLÉMENTAIRE DE L'INTERFACE DIMÈRE-DIMÈRE DE LA TUBULINE PAR UNE COMPLEXITÉ MOLÉCULAIRE AJOUTÉE
  申请人：SCRIPPS RESEARCH INST

  公开号：WO2017210206A1

  公开（公告）日：2017-12-07

  Synthetically-derived and previously inaccessible modifications of 20'-hydroxy-vinca derivative compounds such as vinblastine, vincristine or vindesine are disclosed that are a stunning 100-fold more active than the natural product (IC50's 50-75 pM vs 7 nM, HCT116), and are now accessible as a result of advances in the total synthesis of the natural product. Illustrative new ultra-potent vinblastines bind tubulin with much higher affinity and likely further disrupt the tubulin head-to-tail α/β dimer-dimer interaction by virtue of the strategic placement of an added conformationally well-defined, rigid and extended C20'-urea along the adjacent protein-protein interface. Added molecular complexity was used to markedly enhance target binding and functional biological activity, and represents a general approach to improving the properties of other natural products targeting a protein-protein interaction. A pharmaceutical composition containing an ultra-potent 20'-hydroxy-vinca derivative compound and a method of treating cancerous cells with such a compound are also disclosed.

  合成衍生和以前无法获取的20'-羟基长春碱衍生物化合物的修改被披露，这些化合物如长春碱、长春新碱或长春新素比天然产物活性高出惊人的100倍（IC50为50-75 pM vs 7 nM，HCT116），现在可以通过对天然产物的全合成的进展来获得。说明性的新型超高效长春碱与微管结合的亲和力更高，很可能通过在相邻的蛋白质-蛋白质界面上添加构象明确定、刚性和延伸的C20'-尿素来进一步破坏微管头尾α/β二聚体-二聚体相互作用。增加的分子复杂性被用来显著增强靶标结合和功能生物活性，并代表了改善其他以蛋白质-蛋白质相互作用为靶点的天然产物性质的一般方法。还披露了一种含有超高效20'-羟基长春碱衍生物化合物的药物组合物和用这种化合物治疗癌细胞的方法。
• Hypervalent Iodine(III)-Promoted Intermolecular C–C Coupling of Vindoline with β-Ketoesters and Related Substrates
  作者：Travis C. Turner、Kotaro Shibayama、Dale L. Boger

  DOI：10.1021/ol400135n

  日期：2013.3.1

  regioselective intermolecular coupling reaction of vindoline with a wide range of substrates including β-ketoesters, β-diketones, β-ketoaldehydes, β-ketonitriles, malononitriles, and β-cyanoesters provides an opportunity for the synthesis of vinblastine analogues containing deep-seated changes in the upper velbanamine subunit. The transition-metal-free hypervalent iodine(III)-promoted intermolecular sp3/sp2

  文多林与多种底物的区域选择性分子间偶联反应，包括β-酮酯、β-二酮、β-酮醛、β-酮腈、丙二腈和β-氰酯，为合成含有深层变化的长春碱类似物提供了机会在上部 velbanamine 亚基中。不含过渡金属的高价碘 (III) 促进的分子间 sp 3 / sp 2偶联代表一类特殊的选择性 C-H 活化，直接形成碳 - 碳键，继续生成能够结合长春碱 C16' 甲酯和功能化用于后续不同的杂环引入。
• Syntheses and biological evaluation of vinblastine congeners
  作者：Martin E. Kuehne、William G. Bornmann、Istvan Markó、Yong Qin、Karen L. LeBoulluec、Deborah A. Frasier、Feng Xu、Tshilundu Mulamba、Carol L. Ensinger、Linda S. Borman、Anne E. Huot、Christopher Exon、Fred T. Bizzarro、Julia B. Cheung、Susan L. Bane

  DOI：10.1039/b209990j

  日期：——

  Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at <10−6 M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10−4 M concentrations. An ID50 range of >107 M concentrations was found for L1210 inhibition by these compounds, with the most active 1000× as potent as vinblastine.

  合成了长春碱（VLB）的62个类似物，主要是通过改变二元生物碱中碳甲氧基克拉维胺部分的哌啶环来修改结构，并评估了它们对小鼠L1210白血病和大鼠RCC-2结肠癌细胞的细胞毒性，以及它们在<10^-6 M浓度下抑制微管蛋白聚合、诱导微管蛋白螺旋化和在10^-4 M浓度下解聚微管的能力。这些化合物对L1210的抑制作用表现出>10^7 M的ID50范围，其中最活跃的化合物比长春碱的效力高出1000倍。