灰叶草素; 羟基鱼藤素 | 76-80-2

• 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 - 苯丙烷和聚酮 - 异黄酮类化合物
• 中文名称: 灰叶草素; 羟基鱼藤素
• 中文别名: 羟基鱼藤素；灰叶草素;羟基鱼藤素
• 英文名称: tephrosin
• 英文别名: (6aR,12aR)-tephrosin；(1R,14R)-14-hydroxy-17,18-dimethoxy-7,7-dimethyl-2,8,21-trioxapentacyclo[12.8.0.03,12.04,9.015,20]docosa-3(12),4(9),5,10,15,17,19-heptaen-13-one
• CAS: 76-80-2
• 化学式: C₂₃H₂₂O₇
• 分子量: 410.423
• InChiKey: AQBZCCQCDWNNJQ-AUSIDOKSSA-N

物化性质

• 熔点：
  198° (218-220°)
• 沸点：
  450.42°C (rough estimate)
• 密度：
  1.2284 (rough estimate)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  30
• 可旋转键数：
  2
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  83.4
• 氢给体数：
  1
• 氢受体数：
  7

安全信息

• 危险品标志：
  N
• 安全说明：
  S61
• 危险类别码：
  R50
• WGK Germany：
  3
• 储存条件：
  -20°C

SDS

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SECTION 1: Identification of the substance/mixture and of the company/undertaking
Product identifiers
Product name : Tephrosin
: SMB00172
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. : 76-80-2

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SECTION 2: Hazards identification
Classification of the substance or mixture
Classification according to Regulation (EC) No 1272/2008
Acute aquatic toxicity (Category 1), H400
Chronic aquatic toxicity (Category 1), H410
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
N Dangerous for the R50
environment
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)
Very toxic to aquatic life with long lasting effects.
Precautionary statement(s)
Avoid release to the environment.
Dispose of contents/ container to an approved waste disposal plant.
Supplemental Hazard none
Statements
Other hazards - none

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SECTION 3: Composition/information on ingredients
Substances
Molecular Weight : 410,42 g/mol
CAS-No. : 76-80-2
Hazardous ingredients according to Regulation (EC) No 1272/2008
Component Classification Concentration
Tephrosin
Aquatic Acute 1; Aquatic -
Chronic 1; H410
Hazardous ingredients according to Directive 1999/45/EC
Component Classification Concentration
Tephrosin
N, R50 -
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
no data available
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 dust formation. Avoid breathing vapours, mist or gas. Ensure adequate ventilation.
For personal protection see section 8.
Environmental precautions
Prevent further leakage or spillage if safe to do so. Do not let product enter drains. Discharge into the
environment must be avoided.
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
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.
Recommended storage temperature: -20 °C
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
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
Choose body protection in relation to its type, to the concentration and amount of dangerous
substances, and to the specific work-place., 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 is not required. Where protection from nuisance levels of dusts are desired,
use type N95 (US) or type P1 (EN 143) dust masks. 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. Discharge into
the environment must be avoided.

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SECTION 9: Physical and chemical properties
Information on basic physical and chemical properties
a) Appearance Form: solid
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- log Pow: 3,688
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
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
Very toxic to aquatic life with long lasting 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: 3077 IMDG: 3077 IATA: 3077
UN proper shipping name
ADR/RID: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (Tephrosin)
IMDG: ENVIRONMENTALLY HAZARDOUS SUBSTANCE, SOLID, N.O.S. (Tephrosin)
IATA: Environmentally hazardous substance, solid, n.o.s. (Tephrosin)
Transport hazard class(es)
ADR/RID: 9 IMDG: 9 IATA: 9
Packaging group
ADR/RID: III IMDG: III IATA: III
Environmental hazards
ADR/RID: yes IMDG Marine pollutant: yes IATA: yes
Special precautions for user
Further information
EHS-Mark required (ADR 2.2.9.1.10, IMDG code 2.10.3) for single packagings and combination
packagings containing inner packagings with Dangerous Goods > 5L for liquids or > 5kg for solids.

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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
Further information
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

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

生物活性

Tephrosin 是一种天然类胡萝卜素，具有较强的抗肿瘤活性。它通过诱导受体内化来促进 EGFR 和 ErbB2 的降解。

体外研究

处理 HT-29 细胞 (0-10μM 浓度的 Tephrosin) 可抑制配体诱导和固有磷酸化的 EGFR、ErbB2 和 ErbB3，并相应地抑制下游信号分子如 Akt 和 MAPK（丝裂原活化蛋白激酶 Erk1/2）的激活。

反应信息

• 作为反应物：
  描述：

  灰叶草素; 羟基鱼藤素 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以92%的产率得到(6aR,12R,12aS)-12-deoxo-12-hydroxytephrosin
  参考文献：
  名称：

  羟基化鱼藤素选择性抑制前列腺癌细胞的增殖。

  摘要：

  前列腺癌是男性癌症相关死亡的主要原因之一。因此，确定选择性靶向前列腺癌细胞的新疗法至关重要。最近，据报道，鱼藤类药物鱼藤酮 ( 1 ) 和鱼藤素 ( 2 ) 可以选择性杀死前列腺癌细胞，并且确定线粒体复合物 I 的抑制对其作用机制至关重要。然而，这些疏水性鱼色素很容易穿过血脑屏障，并在动物中诱发帕金森病的特征症状。由于1和2的羟基化衍生物更亲水并且不太容易穿过血脑屏障，因此合成了29种天然和非天然的1和2的羟基化衍生物用于评估。测量了每种衍生物对复合物I的抑制效力(IC 50 )，并预测其疏水性(Slog 10 P)。使用 C4-2 和 C4-2B 前列腺癌细胞以及对照 PNT2 前列腺细胞，在基于细胞的测定中选择和评估 Amorphigenin ( 3 )、dalpanol ( 4 )、二氢 amorphigenin ( 5 ) 和 amorphigenol ( 6 )。这些类鱼色素抑制细胞中的复合物

  DOI：

  10.1021/acs.jnatprod.9b01224
• 作为产物：
  描述：

  3-氟苯酚 在 盐酸 、 N,N-二甲基丙烯基脲 、 potassium dichromate 、 bis(1,5-cyclooctadiene)nickel (0) 、 正丁基锂 、 2,6-二叔丁基吡啶 、 15-冠醚-5 、 四甲基乙二胺 、 三氟化硼乙醚 、 potassium tert-butylate 、 四丁基氟化铵 、 仲丁基锂 、 4-甲基苯磺酸吡啶 、 sodium hydride 、 二异丁基氢化铝 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 、 copper dichloride 、 palladium dichloride 、 三环己基膦 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 1,4-二氧六环 、 乙醚 、 乙醇 、 正己烷 、 二氯甲烷 、 环己烷 、 氘代甲苯 、 水 、 二甲基亚砜 、 甲苯 为溶剂， 反应 27.83h， 生成 灰叶草素; 羟基鱼藤素
  参考文献：
  名称：

  通过芳基氟化物的立体特异性，基团选择性1,2-重排和双SNAr环化合成类胡萝卜素的通用方法

  摘要：

  献给已故的伊藤翔教授 作为《五十周年综合报告》的一部分发行-黄金周年纪念日 抽象的 描述了类胡萝卜素的一般合成方法，其特征在于1）环氧醇的立体有择，基团选择性的1,2-重排，以及2）芳基氟化物的S N Ar氧环化。由d-阿拉伯抗坏血酸分5步制备通常的中间体环氧酮（在途中会生成（-）-鱼藤酮和（-）- deguelin）。还描述了将（–）-地精蛋白转变为氧化的同类物，（–）-邻苯三酚和（+）-12a-表位-邻苯三酚。 描述了类胡萝卜素的一般合成方法，其特征在于1）环氧醇的立体有择，基团选择性的1,2-重排，以及2）芳基氟化物的S N Ar氧环化。由d-阿拉伯抗坏血酸分5步制备通常的中间体环氧酮（在途中会生成（-）-鱼藤酮和（-）- deguelin）。还描述了将（–）-地精蛋白转变为氧化的同类物，（–）-邻苯三酚和（+）-12a-表位-邻苯三酚。

  DOI：

  10.1055/s-0037-1611654

文献信息

• Stereocontrolled semi-syntheses of deguelin and tephrosin
  作者：David A. Russell、Julien J. Freudenreich、Joe J. Ciardiello、Hannah F. Sore、David R. Spring

  DOI：10.1039/c6ob02659a

  日期：——

  We describe stereocontrolled semi-syntheses of deguelin and tephrosin, anti-cancer rotenoids isolated from Tephrosia vogelii. Firstly, we present a new two-step transformation of rotenone into rot-2′-enonic acid via a zinc-mediated ring opening of rotenone hydrobromide. Secondly, following conversion of rot-2′-enonic acid into deguelin, a chromium-mediated hydroxylation provides tephrosin as a single

  我们描述了Deguelin和Tephrosin立体控制的半合成，这是从Tephrosia vogelii中分离出来的抗癌类胡萝卜素。首先，我们提出了一种新的两步法，将鱼藤酮通过锌介导的氢溴酸鱼藤酮开环转化为rot-2'-烯酸。其次，在将rot-2'-烯酸转化为杜格琳之后，铬介导的羟基化作用将特罗泊辛作为单一的非对映异构体提供。提出了一种类似Étard的反应机制来解释立体化学结果。我们合成的地精蛋白和去氧肾上腺素操作简单，可扩展且产率高，与以前的方法相比具有相当大的优势。
• Concise Modular Asymmetric Synthesis of Deguelin, Tephrosin and Investigation into Their Mode of Action
  作者：José Garcia、Sofia Barluenga、Kristin Beebe、Len Neckers、Nicolas Winssinger

  DOI：10.1002/chem.201001080

  日期：2010.8.23

  The concise nature and modularity of the synthesis described for deguelin and tephrosin (retrosynthetic analysis depicted) should facilitate access to labeled analogues to dissect the mechanism of action of this important pharmacophore.

  德桂林和替弗罗辛合成的简明性质和模块性（所描述的逆合成分析）应有助于获得标记的类似物，以剖析这一重要药效团的作用机制。
• Structural Elucidation and Chemical Conversion of Amorphispironone, a Novel Spironone from Amorpha fruticosa, to Rotenoids.
  作者：Hiroki TERADA、Midori KOKUMAI、Takao KONOSHIMA、Mutsuo KOZUKA、Mitsumasa HARUNA、Kazuo ITO、James R ESTES、Leping LI、Hui-Kang WANG、Kuo-Hsiung LEE

  DOI：10.1248/cpb.41.187

  日期：——

  To search for possible antiumor promoters, we carried out an investigation of the leaves of Amorpha fruticosa L. (Leguminosae). The novel spironone type rotenoid, amorphispironone (1), isolated together with four known rotenoids, tephrosin (2), amorphigenin (3), 12a-hydroxyamorphigenin (4) and 12a-hydroxydalpanol (5). Some of these compounds were inhibitors of Epstein-Barr virus early antigen activation induced by 12-O-tetradecanoylphorbol-13-acetate. The structure of 1 was derermined from 2D-NMR spectral data and difference NOE experiments.Amorphispironone (1) was also converted to know rotenoids in order to confirm the proposed structure.

  为了寻找可能的抗肿瘤促进剂，我们对豆科植物果实苜蓿（Amorpha fruticosa L.）的叶子进行了研究。我们分离出了新型螺旋酮类 rotenoid——果实螺旋酮（amorphispironone，1），同时还分离出四种已知的 rotenoid：特弗罗辛（tephrosin，2）、果实苷（amorphigenin，3）、12a-羟基果实苷（12a-hydroxyamorphigenin，4）和12a-羟基达尔潘醇（12a-hydroxydalpanol，5）。这些化合物中有些是12-O-四十烷酯-13-乙酸诱导的埃普斯坦-巴尔病毒早期抗原活化的抑制剂。1的结构是通过二维核磁共振（2D-NMR）光谱数据和差异NOE实验确定的。果实螺旋酮（1）还被转换为已知的 rotenoid，以确认其提议的结构。
• Deguelin as a chemopreventive agent for lung cancer
  申请人：Lee Ho-Young

  公开号：US20060128792A1

  公开（公告）日：2006-06-15

  The present invention provides the chemopreventive agent deguelin, a natural product isolated from Mundulea serica (Leguminosae), and derivatives thereof, for use in combination with a second agent for inhibiting growth premalignant and malignant lung cancer cells by causing G2/M arrest and apoptosis. Thus, the present invention provides deguelin-based combination therapies for the treatment and prevention of lung cancer. The second agent of the present invention may, in particular, be an inhibitor of the P13K, MAPK or JNK signaling pathways, or a chemotherapeutic agent, or radiotherapeutic agent.

  本发明提供了一种化学预防剂deguelin，它是从丝光木属（豆科）中分离出的一种天然产物及其衍生物，用于与第二种制剂结合使用，通过引起G2/M阻滞和凋亡来抑制恶性和前恶性肺癌细胞的生长。因此，本发明提供了基于deguelin的联合治疗方法，用于治疗和预防肺癌。本发明的第二种制剂可能特别是P13K、MAPK或JNK信号通路的抑制剂，或化疗剂，或放射治疗剂。
• [DE] VERWENDUNG MINDESTENS EINER SÄURE DES ZITRONENSÄURE-KREISLAUFS IN KOMBINATION MIT GLYCERIN ALS SCHÄDLINGSBEKÄMPFUNGSMITTEL<br/>[EN] USE OF AT LEAST ONE ACID FROM THE CITRIC ACID CYCLE COMBINED WITH GLYCERINE AS A PESTICIDE<br/>[FR] UTILISATION D'AU MOINS UN ACIDE DU CYCLE ACIDE CITRIQUE EN COMBINAISON AVEC DE LA GLYCERINE, COMME AGENT DE LUTTE CONTRE LES PARASITES
  申请人：BIOLINK TECHNOLOGIES AG

  公开号：WO1999063818A1

  公开（公告）日：1999-12-16

  (DE) Die vorliegende Erfindung betrifft die Verwendung mindestens einer Säure des Zitronensäurekreislaufs in Kombination mit Glycerin zur Schädlingsbekämpfung.(EN) The present invention relates to the use of at least one acid from the citric acid cycle combined with glycerine in order to control pests.(FR) L'invention concerne l'utilisation d'un acide du cycle de l'acide citrique en combinaison avec de la glycérine pour lutter contre les parasites.

  (德语)这项发明涉及利用柠檬酸循环中的一种酸与甘油结合以防治害虫。 (英文)这项发明涉及利用柠檬酸循环中的一种酸与甘油结合以防治害虫。 (法语)这项发明涉及利用柠檬酸循环酸与甘油来防治害虫。