青霉酸 | 90-65-3

• 物质功能分类: 化学试剂 - 有机试剂 - 脂肪酸
• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 酮酸及其衍生物
• 中文名称: 青霉酸
• 英文名称: 3-methoxy-5-methyl-4-oxohexa-2,5-dienoic acid
• CAS: 90-65-3
• 化学式: C₈H₁₀O₄
• 分子量: 170.16
• InChiKey: VOUGEZYPVGAPBB-UHFFFAOYSA-N

物化性质

• 熔点：
  83-87 °C
• 沸点：
  219.79°C (rough estimate)
• 密度：
  1.1456 (rough estimate)
• 溶解度：
  二甲基亚砜：>10mg/mL
• 颜色/状态：
  NEEDLES FROM PETROLEUM ETHER
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 稳定性/保质期：
  1. 常温常压下稳定，避免与不相容材料接触。
  2. 与强氧化剂反应。
  3. 存在于烟叶中。
  4. 高毒，疑为致癌物。

计算性质

• 辛醇/水分配系数(LogP)：
  0.9
• 重原子数：
  12
• 可旋转键数：
  4
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  63.6
• 氢给体数：
  1
• 氢受体数：
  4

ADMET

代谢

青霉素酸是已知与蓝纹奶酪相关的青霉菌菌株的代谢产物。

PENICILLIC ACID IS A KNOWN METABOLITE OF STRAINS OF PENICILLIUM ROQUEFORTI ASSOCIATED WITH BLUE-VEINED CHEESES.

来源:Hazardous Substances Data Bank (HSDB)

代谢

百分之十的青霉素酸代谢物在小鼠雄性中检测为葡萄糖醛酸苷结合物。尿液、血浆和胆汁中的所有代谢物都比原化合物更具极性。主要的代谢物是谷胱甘肽或半胱氨酸的结合物或衍生物。

TEN PERCENT OF PENICILLIC ACID METABOLITES IN MALE MICE WERE DETECTED AS GLUCURONIDE CONJUGATES. ALL METABOLITES IN URINE, PLASMA AND BILE WERE MORE POLAR THAN THE PARENT COMPOUND. THE MAJOR METABOLITES WERE CONJUGATES OR DERIVATIVES OF GLUTATHIONE OR CYSTEINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在小鼠肝脏匀浆的亚细胞组分中，青酸与谷胱甘肽发生酶促和非酶促反应；每个反应都同等重要。当没有谷胱甘肽时，各种肝脏亚细胞组分的新陈代谢基本上是非酶促的，但是当谷胱甘肽可用时，新陈代谢增加了。在谷胱甘肽的存在下，30分钟内添加的青酸有75%被生物转化为不能被有机溶剂提取且比青酸极性更大的代谢物。

IN SUBCELLULAR FRACTIONS OF MOUSE LIVER HOMOGENATES, PENICILLIC ACID REACTS WITH GLUTATHIONE BOTH ENZYMICALLY AND NONENZYMICALLY; EACH REACTION WAS OF EQUAL IMPORTANCE. METABOLISM BY VARIOUS HEPATIC SUBCELLULAR FRACTIONS WAS ESSENTIALLY NONENZYMIC WHEN GLUTATHIONE WAS ABSENT, BUT METABOLISM WAS INCREASED WHEN GLUTATHIONE WAS AVAILABLE. IN THE PRESENCE OF GLUTATHIONE, 75% OF ADDED PENICILLIC ACID WAS BIOTRANSFORMED WITHIN 30 MINUTES TO METABOLITES NOT EXTRACTABLE WITH ORGANIC SOLVENTS AND MORE POLAR THAN PENICILLIC ACID.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据有限。总体评估：第3组：该物质对人类致癌性不可分类。

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌剂：青霉酸

IARC Carcinogenic Agent:Penicillic acid

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：无法归类其对人类致癌性

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专著：第10卷：（1976年）一些天然存在的物质

IARC Monographs:Volume 10: (1976) Some Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

毒理性

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

来源:Haz-Map, Information on Hazardous Chemicals and Occupational Diseases

吸收、分配和排泄

体内和体外研究表明，红血细胞对(14)C-青霉酸的摄取显著，随着时间的推移（1-4小时），与膜组分相关的放射性活性显著增加。然而，大部分的血细胞活性是在细胞内的。肝脏组分中的(14)C放射性浓度占RNA-DNA和蛋白质组分的1.5%。与这些组分相关的(14)C活性的水平随着时间的推移（24小时）而增加。对大鼠体内[(14)C]青霉酸代谢的研究表明，大量的放射性物质通过尿液排出（7天后占给药剂量的82%）。给药后2小时，胆汁代谢物占给药剂量的10%。

IN VIVO AND IN VITRO STUDIES SHOWED SIGNIFICANT UPTAKE OF (14)C-PENICILLIC ACID BY RED BLOOD CELLS AND A SIGNIFICANT INCREASE IN RADIOACTIVITY ASSOCIATED WITH THE MEMBRANE FRACTION WITH TIME (1-4 HOURS). HOWEVER, THE MAJORITY OF THE BLOOD CELL ACTIVITY WAS INTRACELLULAR. THE (14)C-RADIOACTIVITY CONCENTRATION IN LIVER FRACTIONS (1.5% OF THE RNA-DNA AND PROTEIN FRACTIONS. THE LEVEL OF THE (14)C ACTIVITY ASSOCIATED WITH THESE FRACTIONS INCREASED WITH TIME (24 HR). STUDIES OF THE IN VIVO METABOLISM OF [(14)C] PENICILLIC ACID BY RATS SHOWED THAT A SIGNIFICANT AMOUNT OF RADIOACTIVITY WAS EXCRETED IN THE URINE (82% OF THE ADMINISTERED DOSE AFTER 7 DAYS). BILIARY METABOLITES ACCOUNTED FOR 10% OF ADMINISTERED DOSE 2 HOURS AFTER ADMINISTRATION.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,T
• 安全说明：
  S24/25,S26,S37/39
• 危险类别码：
  R36/37/38
• 海关编码：
  2918990090
• 危险品运输编号：
  UN 2811
• 包装等级：
  III
• 危险类别：
  6.1(b)

SDS

Name:	Penicillic Acid Material Safety Data Sheet
Synonym:	Gamma-Keto-Beta-Methoxy-Delta-Methylene-Delta(sup alpha)-Hexenoic Acid; Kyselina Penicilova; 3-Methoxy-5-Methyl-4-Oxo-2,5-Hexadienoic Acid
CAS:	90-65-3

Section 1 - Chemical Product MSDS Name:Penicillic Acid Material Safety Data Sheet
Synonym:Gamma-Keto-Beta-Methoxy-Delta-Methylene-Delta(sup alpha)-Hexenoic Acid; Kyselina Penicilova; 3-Methoxy-5-Methyl-4-Oxo-2,5-Hexadienoic Acid

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Section 2 - COMPOSITION, INFORMATION ON INGREDIENTS

CAS#	Chemical Name	content	EINECS#
90-65-3	Penicillic Acid	ca 100	202-008-1

Hazard Symbols: T
Risk Phrases: 23/24/25

---

Section 3 - HAZARDS IDENTIFICATION
EMERGENCY OVERVIEW
Toxic by inhalation, in contact with skin and if swallowed.Cancer suspect agent.The toxicological properties of this material have not been fully investigated.
Potential Health Effects
Eye:
May cause eye irritation.
Skin:
May cause skin irritation.
Ingestion:
May cause irritation of the digestive tract. The toxicological properties of this substance have not been fully investigated.
Inhalation:
May cause respiratory tract irritation. The toxicological properties of this substance have not been fully investigated.
Chronic:
May cause cancer according to animal studies. Adverse reproductive effects have been reported in animals.

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Section 4 - FIRST AID MEASURES
Eyes: Flush eyes with plenty of water for at least 15 minutes, occasionally lifting the upper and lower eyelids. Get medical aid.
Skin:
Get medical aid. Flush skin with plenty of water for at least 15 minutes while removing contaminated clothing and shoes. Wash clothing before reuse.
Ingestion:
Get medical aid. Do NOT induce vomiting. If conscious and alert, rinse mouth and drink 2-4 cupfuls of milk or water.
Inhalation:
Remove from exposure and move to fresh air immediately. If not breathing, give artificial respiration. If breathing is difficult, give oxygen. Get medical aid.
Notes to Physician:

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Section 5 - FIRE FIGHTING MEASURES
General Information:
As in any fire, wear a self-contained breathing apparatus in pressure-demand, MSHA/NIOSH (approved or equivalent), and full protective gear. During a fire, irritating and highly toxic gases may be generated by thermal decomposition or combustion.
Extinguishing Media:
Use agent most appropriate to extinguish fire. Use water spray, dry chemical, carbon dioxide, or appropriate foam.

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Section 6 - ACCIDENTAL RELEASE MEASURES
General Information: Use proper personal protective equipment as indicated in Section 8.
Spills/Leaks:
Vacuum or sweep up material and place into a suitable disposal container. Clean up spills immediately, observing precautions in the Protective Equipment section. Avoid generating dusty conditions.
Provide ventilation.

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Section 7 - HANDLING and STORAGE
Handling:
Wash thoroughly after handling. Use with adequate ventilation.
Minimize dust generation and accumulation. Avoid contact with eyes, skin, and clothing. Keep container tightly closed. Avoid ingestion and inhalation.
Storage:
Store in a tightly closed container. Store in a cool, dry, well-ventilated area away from incompatible substances.

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Section 8 - EXPOSURE CONTROLS, PERSONAL PROTECTION
Engineering Controls:
Facilities storing or utilizing this material should be equipped with an eyewash facility and a safety shower. Use adequate ventilation to keep airborne concentrations low.
Exposure Limits CAS# 90-65-3: Personal Protective Equipment Eyes: Wear appropriate protective eyeglasses or chemical safety goggles as described by OSHA's eye and face protection regulations in 29 CFR 1910.133 or European Standard EN166.
Skin:
Wear appropriate protective gloves to prevent skin exposure.
Clothing:
Wear appropriate protective clothing to prevent skin exposure.
Respirators:
A respiratory protection program that meets OSHA's 29 CFR 1910.134 and ANSI Z88.2 requirements or European Standard EN 149 must be followed whenever workplace conditions warrant respirator use.

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Section 9 - PHYSICAL AND CHEMICAL PROPERTIES

Physical State: Powder
Color: white
Odor: Not available.
pH: Not available.
Vapor Pressure: Not available.
Viscosity: Not available.
Boiling Point: Not available.
Freezing/Melting Point: 86 deg C
Autoignition Temperature: Not applicable.
Flash Point: Not applicable.
Explosion Limits, lower: Not available.
Explosion Limits, upper: Not available.
Decomposition Temperature:
Solubility in water:
Specific Gravity/Density:
Molecular Formula: C8H10O4
Molecular Weight: 170.16

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Section 10 - STABILITY AND REACTIVITY
Chemical Stability:
Stable at room temperature in closed containers under normal storage and handling conditions.
Conditions to Avoid:
Incompatible materials, dust generation, excess heat.
Incompatibilities with Other Materials:
Strong bases, strong oxidizing agents.
Hazardous Decomposition Products:
Carbon monoxide, irritating and toxic fumes and gases, carbon dioxide.
Hazardous Polymerization: Has not been reported

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Section 11 - TOXICOLOGICAL INFORMATION
RTECS#:
CAS# 90-65-3: MM2625000 LD50/LC50:
CAS# 90-65-3: Oral, mouse: LD50 = 600 mg/kg.
Carcinogenicity:
Penicillic Acid - Not listed by ACGIH, IARC, or NTP.
Other:
See actual entry in RTECS for complete information.

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Section 12 - ECOLOGICAL INFORMATION

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Section 13 - DISPOSAL CONSIDERATIONS
Dispose of in a manner consistent with federal, state, and local regulations.

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Section 14 - TRANSPORT INFORMATION

IATA
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.*
Hazard Class: 6.1
UN Number: 2811
Packing Group: II
IMO
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing Group: II
RID/ADR
Shipping Name: TOXIC SOLID, ORGANIC, N.O.S.
Hazard Class: 6.1
UN Number: 2811
Packing group: II

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Section 15 - REGULATORY INFORMATION

European/International Regulations
European Labeling in Accordance with EC Directives
Hazard Symbols: T
Risk Phrases:
R 23/24/25 Toxic by inhalation, in contact with skin
and if swallowed.
Safety Phrases:
S 24/25 Avoid contact with skin and eyes.
S 28A After contact with skin, wash immediately with
plenty of water.
S 37 Wear suitable gloves.
S 45 In case of accident or if you feel unwell, seek
medical advice immediately (show the label where
possible).
WGK (Water Danger/Protection)
CAS# 90-65-3: No information available.
Canada
None of the chemicals in this product are listed on the DSL/NDSL list.
CAS# 90-65-3 is not listed on Canada's Ingredient Disclosure List.
US FEDERAL
TSCA
CAS# 90-65-3 is not listed on the TSCA inventory.
It is for research and development use only.

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SECTION 16 - ADDITIONAL INFORMATION
N/A

制备方法与用途

青霉酸是什么

青霉酸（penicillic acid）主要在软毛青霉中合成，是一种由圆弧青霉菌产生的代谢产物，在饲料中的最高含量可达到2%。这种毒素是危害养殖业的常见霉菌之一，长期饲喂含青霉酸的饲料能使动物肝脏肿大、肝细胞变性，并抑制动物细胞DNA合成；严重的甚至会导致动物细胞DNA断裂。此外，青霉酸与其他霉菌毒素共同作用时还会产生联合毒性。

青霉酸（PA）是由Alsberg和Black在1913年发现并命名的，主要在软毛青霉中合成的一种青霉毒素。它广泛存在于许多农产品中，如玉米、干豆、动物饲料等。研究发现，过量摄入PA会引起多种毒性症状，包括肝毒性、细胞毒性和肺泡毒性，并且具有致癌作用。通过食物链富集的PA对人体健康构成威胁，因此建立一套行之有效的快速检测方法非常重要。

青霉酸的主要用途

青霉酸主要是由曲霉菌和青霉菌产生的次级代谢产物，拥有广泛的生物活性。

青霉酸的生物活性

Penicillic acid 是一种聚酮化合物霉菌毒素，在体外对大鼠肺泡巨噬细胞 (AM) 具有细胞毒性。它通过阻断 caspase-8 自我加工来抑制 Fas 配体诱导的细胞凋亡。

类别：有毒物质
毒性分级：高毒
急性毒性：腹腔—大鼠 LD50 90 毫克/公斤；口服—小鼠 LD50: 600 毫克/公斤
可燃性危险特性：可燃，火场排出辛辣刺激烟雾
储运特性：库房低温、通风、干燥
灭火剂：水、二氧化碳、干粉、砂土

文献信息

• [EN] KETAL ESTERS OF ANHYDROPENTITOLS AND USES THEREOF<br/>[FR] CÉTO-ESTERS D'ANHYDROPENTITOLS ET LEURS UTILISATIONS
  申请人：XLTERRA INC

  公开号：WO2010138842A1

  公开（公告）日：2010-12-02

  The present disclosure relates to the preparation of ketal compounds from anhydropentitols and oxocarboxylates; derivatives, homopolymers, and copolymers thereof; and various compositions, formulations, and articles derived therefrom.

  本公开涉及从无水戊糖醇和羰基羧酸酯制备缩酮化合物；以及它们的衍生物、同聚物和共聚物；以及由此衍生的各种组合物、配方和制品。
• [EN] METHOD OF MAKING KETALS AND ACETALS<br/>[FR] PROCÉDÉ DE FABRICATION DE CÉTALS ET D'ACÉTALS
  申请人：SEGETIS INC

  公开号：WO2009048874A1

  公开（公告）日：2009-04-16

  The reaction of alcohols with oxocarboxylates to form acetals or ketals is catalyzed by unexpectedly low levels of protic acids. By employing low acid catalyst levels compared to amounts conventionally used, rapid formation of acetal or ketal is facilitated while the formation of oxocarboxylate esters is minimized. Further employing a significant molar excess of oxocarboxylate in conjunction with low acid catalyst level gives rise to the rapid and clean formation of acetals and ketals from oxocarboxylates and alcohols.

  醇与羰基羧酸酯反应形成缩醛或缩酮，其催化剂是意外地低水平的质子酸。通过使用比传统用量低的酸催化剂水平，促进了缩醛或缩酮的快速形成，同时最小化了羰基羧酸酯的形成。进一步采用大量的羰基羧酸酯与低水平酸催化剂结合，可以使羰基羧酸酯和醇快速而干净地形成缩醛和缩酮。
• Hybrid Compounds And Methods Of Making And Using The Same
  申请人：Pan Wenxi

  公开号：US20140171438A1

  公开（公告）日：2014-06-19

  The present disclosure provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, malaria, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; killing or inhibiting the growth of a Plasmodium species; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative.

  本公开提供化合物或其药学上可接受的盐，用于抑制微生物的生长；治疗患有微生物感染、疟疾、粘膜炎、眼部感染、耳部感染、癌症或分枝杆菌感染的哺乳动物；杀灭或抑制疟原虫的生长；抑制分枝杆菌的生长；调节哺乳动物的免疫反应；或对抗非分馏肝素、低分子量肝素或肝素/低分子量肝素衍生物。
• [EN] CYCLIC COMPOUNDS AND METHODS OF MAKING AND USING THE SAME<br/>[FR] COMPOSÉS CYCLIQUES ET LEURS PROCÉDÉS DE FABRICATION ET D'UTILISATION
  申请人：POLYMEDIX INC

  公开号：WO2013090185A1

  公开（公告）日：2013-06-20

  The present invention provides compounds, or pharmaceutically acceptable salts thereof, for inhibiting the growth of a microbe; treating a mammal having a microbial infection, mucositis, an ophthalmic infection, an otic infection, a cancer, or a Mycobacterium infection; inhibiting the growth of a Mycobacterium species; modulating an immune response in a mammal; or antagonizing unfractionated heparin, low molecular weight heparin, or a heparin/low molecular weight heparin derivative.

  本发明提供了用于抑制微生物生长的化合物或其药学上可接受的盐；用于治疗患有微生物感染、口腔炎、眼科感染、耳科感染、癌症或结核分枝杆菌感染的哺乳动物；用于抑制结核分枝杆菌物种的生长；用于调节哺乳动物的免疫反应；或用于拮抗非分级肝素、低分子肝素或肝素/低分子肝素衍生物。
• Synthetic Mimetics Of Host Defense And Uses Thereof
  申请人：DeGrado William F.

  公开号：US20100105703A1

  公开（公告）日：2010-04-29

  The present invention provides arylamide compounds and methods of making and using them as antibiotics.

  本发明提供了芳基酰胺化合物及其作为抗生素的制备和使用方法。