茴芹内酯 | 131-12-4

• 物质功能分类: 天然产物 - 香豆素
• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 香豆素及其衍生物
• 中文名称: 茴芹内酯
• 中文别名: 茴芹香豆素
• 英文名称: pimpinellin
• 英文别名: 5,6-dimethoxyfuro[2,3-h]chromen-2-one
• CAS: 131-12-4
• 化学式: C₁₃H₁₀O₅
• 分子量: 246.219
• InChiKey: BQPRWZCEKZLBHL-UHFFFAOYSA-N

物化性质

• 熔点：
  119°
• 沸点：
  441.0±45.0 °C(Predicted)
• 密度：
  1.352±0.06 g/cm3(Predicted)
• 溶解度：
  溶于氯仿、二氯甲烷、乙酸乙酯、DMSO、丙酮等。
• LogP：
  1.477 (est)
• 颜色/状态：
  Off-white needles from methylene chloride/hexane
• 蒸汽压力：
  1.20X10-6 mm Hg at 25 °C (est)
• 碰撞截面：
  146.4 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine and drug standards]

计算性质

• 辛醇/水分配系数(LogP)：
  2.3
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.15
• 拓扑面积：
  57.9
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

毒理性

• 毒性总结

鉴定和使用：白芷素是白芷根的一个组成部分，白芷是一种在中国广泛用于治疗与过敏性炎症相关症状的药用植物。人体研究：光致接触测试显示白芷素具有光毒性。作用光谱研究表明，在330-335纳米范围内光敏感性达到峰值。它抑制了人类癌细胞的生长。此外，白芷素通过诱导肿瘤细胞凋亡来抑制肿瘤细胞的生长。动物研究：白芷素在体外念珠菌测试中显示出光毒性。

IDENTIFICATION AND USE: Pimpinellin is a component of Angelica dahurica roots which is a medicinal plant widely used in China for the treatment of symptoms related to allergic inflammation. HUMAN STUDIES: Photoepicutaneous testing showed phototoxic effects from pimpinellin. Action spectrum studies demonstrated peak photosensitivity in the range 330-335 nm. It inhibited growth of human carcinoma cells. Moreover, pimpinellin inhibited the growth of tumor cells via the induction of tumor cell apoptosis. ANIMAL STUDIES: Pimpinellin was phototoxic the in vitro Candida test.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 毒性总结

pimpinellin 作为具有 GABA 受体活性的蛋白质的拮抗剂 (L579)。许多呋喃香豆素的的作用机制是基于它们能够与 DNA 和其他细胞组分如 RNA、蛋白质以及膜中存在的几种蛋白质（如磷脂酶 A2 和 C、Ca 依赖性和 cAMP 依赖性蛋白激酶以及表皮生长因子）形成光加合物。呋喃香豆素插入 DNA 的碱基对之间，并在紫外线 A 辐照后给出环加合物 (L579)。

Pimpinellin acts as antagonist of proteins with GABA receptor activity (L579). The mechanism of action many furocoumarins is based on their ability to form photoadducts with DNA and other cellular components such as RNA, proteins, and several proteins found in the membrane such as phospholipases A2 and C, Ca-dependent and cAMPdependent protein-kinase and epidermal growth factor. Furocoumarins intercalate between base pairs of DNA and after ultraviolet-A irradiation, giving cycloadducts. (L579).

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 致癌物分类

未列入国际癌症研究机构(IARC)名录。IARC评估了其他呋喃香豆素类物质，将8-甲氧基补骨脂素归类为对人类致癌(第1组)，5-甲氧基补骨脂素归类为可能对人类致癌(第2A组)，以及其他某些呋喃香豆素类物质归类为对人类致癌性无法分类(第3组)。(L135)

Not listed by IARC. IARC has assessed other furocoumarins, classifying 8-methoxypsoralen as carcinogenic to humans (Group 1), 5-methoxypsoralen as possibly carcinogenic to humans (Group 2A), and certain other furocoumarins as not being classifiable as to their carcinogenicity to humans (Group 3). (L135)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 健康影响

呋喃香豆素中的8-甲氧基补骨脂素对人类具有致癌性，5-甲氧基补骨脂素也可能具有致癌性（L135）。一些基于小鼠研究的证据表明，当与UVA辐射暴露结合时，其他呋喃香豆素也具有致癌性（A15105）。SKLM认为，从食用含有呋喃香豆素的食物中产生的额外皮肤癌风险，这些食物的呋喃香豆素含量远低于光毒性剂量范围，因此是不显著的。然而，对于某些食物，尤其是芹菜和欧防风，由于储存、加工和生产条件的影响，可能会出现光毒性剂量的消费，从而导致呋喃香豆素浓度显著增加（L2157）。已知呋喃香豆素光化学疗法会诱导多种副作用，包括红斑、水肿、色素沉着过度和皮肤过早老化。呋喃香豆素的所有光生物效应都源于它们的光化学反应。因为许多可溶于饮食或水的呋喃香豆素是细胞色素P450的强抑制剂，所以它们与其他药物一起服用时也会引起不良反应。这是白癜风患者发生光毒性的原因（L579）。

The furocoumarin 8-methoxypsoralen is carcinogenic to humans, and possibly 5-methoxypsoralen as well (L135). There is some evidence from mouse studies that other furocoumarins are carcinogenic when combined with exposure to UVA radiation (A15105). The SKLM regards the additional risk of skin cancer arising from the consumption of typical quantities of furocoumarin-containing foods, which remain significantly below the range of phototoxic doses, as insignificant. However, the consumption of phototoxic quantities cannot be ruled out for certain foods, particularly celery and parsnips, that may lead to significant increases in furocoumarin concentrations, depending on the storage, processing and production conditions. (L2157) Furocoumarin photochemotherapy is known to induce a number of side-effects including erythema, edema, hyperpigmentation, and premature aging of skin. All photobiological effects of furocoumarins result from their photochemical reactions. Because many dietary or water soluble furocoumarins are strong inhibitors of cytochrome P450s, they will also cause adverse drug reactions when taken with other drugs. Cause of phototoxicity in patient with vitiligo. (L579)

来源:Toxin and Toxin Target Database (T3DB)

毒理性

• 相互作用

对一名白癜风患者光反应的研究结果如下：在UVB区域的最低红斑剂量（MED）大约是皮肤类型II人群的1/3。使用呋喃香豆素（补骨脂素）增加了在300-310 nm的光耐受性，提高了1个MED。以聚伞花素为光敏剂的行动光谱研究表明，有效成分的强弱顺序为：伯格普坦、聚伞花素、当归素和 sphondin。在325-350 nm时的效果最高，最大值在330-335 nm。最近发现聚伞花素具有光毒性，但这是首次报告sphondin的行动光谱。

Investigations on light reactions in a patient with vitiligo are presented. The minimal erythema dose (MED) in the UVB area was approximately 1/3 of that in persons of skin type II. The application of furocoumarins (psoralens) increased light tolerance by 1 MED at 300-310 nm. Action spectrum studies with furocoumarins from Heracleum laciniatum showed the following order of potency: bergapten, pimpinellin, angelicin and sphondin. The efficacy was highest at 325-350 nm, with maxima at 330-335 nm. Pimpinellin was recently found to be phototoxic, but an action spectrum of sphondin is reported for the first time.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 海关编码：
  2932999099
• 危险性防范说明：
  P302+P352,P333+P313,P321,P261,P272,P280,P363,P501
• 危险性描述：
  H317

制备方法与用途

生物活性

Pimpinellin 是 Cyrtomium fortunei (J.) 的一种成分，能够通过诱导肿瘤细胞凋亡（apoptosis）来抑制肿瘤细胞的生长。

体外研究

Pimpinellin 对 MGC-803、PC3 和 A375 三种肿瘤细胞具有强烈的细胞毒性作用，IC50 值分别为 14.4±0.3 μM、20.4±0.5 μM 和 29.2±0.6 μM。Pimpinellin 通过诱导 MGC-803 细胞凋亡抑制其生长，72 小时后在 20 μM 浓度下，凋亡比率为 27.44%。

化学性质

Pimpinellin 是一种浅黄色针状结晶，可溶于甲醇、乙醇和 DMSO 等有机溶剂。它来源于牛尾独活。

用途

茴芹内酯具有抗菌作用，并可用于含量测定、鉴定及药理实验等。

反应信息

• 作为反应物：
  描述：

  茴芹内酯 在 氢氧化钾 、 sodium amalgam 、 碳酸氢钠 、 丙酮 作用下， 生成 3-(4,6,7-trimethoxy-benzofuran-5-yl)-propionic acid
  参考文献：
  名称：

  Wessely; Kallab, Monatshefte fur Chemie, 1932, vol. 59, p. 161,170

  摘要：

  DOI：
• 作为产物：
  描述：

  5-<2-(methoxycarbonyl)-1-ethynyl>-4,6,7-trimethoxybenzofuran 在 Lindlar's catalyst ammonium cerium(IV) nitrate 、 氢气 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 、 乙腈 为溶剂， 反应 5.25h， 生成 茴芹内酯
  参考文献：
  名称：

  Efficient synthesis of furochromone and furocoumarin natural products (khellin, pimpinellin, isophellopterin) by thermal rearrangement of 4-furyl-4-hydroxycyclobutenones

  摘要：

  DOI：

  10.1021/jo00253a002

文献信息

• Total Syntheses of the Coumarin-Containing Natural Products Pimpinellin and Fraxetin Using Au(I)-Catalyzed Intramolecular Hydroarylation (IMHA) Chemistry
  作者：Aymeric Cervi、Paul Aillard、Nourallah Hazeri、Laurent Petit、Christina L. L. Chai、Anthony C. Willis、Martin G. Banwell

  DOI：10.1021/jo401583q

  日期：2013.10.4

  and 2, respectively) have been synthesized by Au(I)-catalyzed intramolecular hydroarylation (IMHA) of the relevant aryl propiolate esters (e.g., 13), which were themselves formed by reaction of the corresponding phenols with either 3-(trimethylsilyl)propiolic acid or propiolic acid and N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride or dicyclohexylcarbodiimide. (±)-Purpurasol (3) was readily

  标题天然产物（分别为1和2）是通过Au（I）催化的相关丙酸芳基酯（例如13）的分子内氢芳基化反应（IMHA）合成的，它们本身是由相应的酚与以下任何一种反应生成的3-（三甲硅烷基）丙炔酸或丙炔酸和ñ - （3-二甲基氨基丙基） - ñ '-ethylcarbodiimide盐酸盐或二环己基。（±）-Purpurasol（3）很容易通过既定程序从fraxetin（2）衍生而来。
• Process for production of vinyl chloride polymer
  申请人：Shin-Etsu Chemical Co., Ltd.

  公开号：EP0172427A2

  公开（公告）日：1986-02-26

  This process is a process for production of a vinyl chloride polymer by suspension polymerization or emulsion polymerization of vinyl chloride monomer or a mixture of vinyl chloride monomer with a vinyl monomer copolymerizable with said vinyl chloride monomer in an aqueous medium, characterized in that the polymerization is carried out in a polymerizer, the inner wall surface and portions of the auxiliary equipment thereof which may come into contact with the monomer during polymerization being previously coated with a scaling preventive comprising at least one selected from dyes, pigments and aromatic or heterocyclic compounds having at least 5 conjugated π bonds, while controlling the chloride ion concentration in the reaction mixture to not higher than 100 ppm. According to said process, scaling onto the inner wall surface of a polymerizer, etc. during polymerization can be prevented effectively and surely.

  该工艺是通过氯乙烯单体或氯乙烯单体与可与所述氯乙烯单体共聚的乙烯基单体混合物在水介质中进行悬浮聚合或乳液聚合来生产氯乙烯聚合物的工艺，其特征在于聚合是在聚合器中进行的、内壁表面及其辅助设备中可能在聚合过程中与单体接触的部分事先涂上一层防垢剂，该防垢剂至少包括一种选自染料、颜料和至少有 5 个共轭 π 键的芳香族或杂环化合物的防垢剂，同时控制反应混合物中的氯离子浓度不高于 100 ppm。根据上述工艺，可有效、可靠地防止聚合过程中聚合器等内壁表面结垢。
• 5-methoxypsoralen and other furocoumarins as jet lag suppressants
  申请人：Goupil, Jean-Jacques

  公开号：EP0352198A2

  公开（公告）日：1990-01-24

  Disclosed is use of 5-methoxypsoralen and other furocoumarins to prevent and suppress the symptoms of jet lag.

  公开了 5-甲氧基补骨脂素 和其他呋喃香豆素来预防和抑制时差症状。
• Polymerization process characterized by a two layer coating against scale formation deposited using a steam carrier
  申请人：SHIN-ETSU CHEMICAL CO., LTD.

  公开号：EP0934955A1

  公开（公告）日：1999-08-11

  An improved process for producing a polymer by polymerizing a monomer having an ethylenic double bond in a polymerization vessel having a polymer scale preventive coating film on its inner wall surfaces, etc. is provided. The coating film is formed by coating a first coating liquid containing a compound selected from the group consisting of an aromatic compound having 5 or more conjugated π bonds and a heterocyclic compound having 5 or more conjugated π bonds, and then coating a second coating liquid on the first layer. The first and second coating liquids are applied by means of steam as a carrier. The second layer has a surface having a contact angle to water of less than 60° after its surface has been brought into contact with a solution of mixture of water and a vinyl chloride monomer in a weight ratio of 1:1, at 50°C for 1 hour. This process can shorten the time for forming the coating film to improve productivity, can improve the effect of preventing adhesion of polymer scale, can make colored particles less mix into polymer products obtained by this process, can lessen fish eyes and initial discoloring of formed products and can improve the quality of polymeric products and their formed or molded products.

  本发明提供了一种通过在聚合容器中聚合具有乙烯双键的单体来生产聚合物的改进工艺，该聚合容器的内壁表面等处具有聚合物防垢涂膜。该涂膜是通过涂覆第一涂覆液形成的，第一涂覆液含有选自具有 5 个或更多共轭 π 键的芳香族化合物和具有 5 个或更多共轭 π 键的杂环化合物的一组化合物，然后在第一层上涂覆第二涂覆液。第一种和第二种涂覆液通过蒸汽作为载体进行涂覆。第二层表面与水和氯乙烯单体重量比为 1:1 的混合物溶液在 50°C 下接触 1 小时后，其表面与水的接触角小于 60°。这种工艺可以缩短涂膜的形成时间，从而提高生产率；可以提高防止聚合物鳞片附着的效果；可以使有色颗粒较少地混入通过这种工艺获得的聚合物产品中；可以减少成型产品的鱼眼和初期褪色现象；可以提高聚合物产品及其成型或模塑产品的质量。
• Process for producing a polymer by polymerization of a monomer having an ethylenic double bond
  申请人：SHIN-ETSU CHEMICAL CO., LTD.

  公开号：EP1063242A1

  公开（公告）日：2000-12-27

  A process for producing a polymer by polymerizing in a polymerization vessel a monomer having an ethylenic double bond is provided. In this process, the polymerization vessel has a polymer scale preventive coating film on its inner wall surfaces and other surfaces with which the monomer comes into contact during polymerization. The coating film is formed by coating a first coating liquid containing a compound selected from the group consisting of an aromatic compound having 5 or more conjugated π bonds and a heterocyclic compound having 5 or more conjugated π bonds and a second coating liquid containing at least one hydrophilic compound selected from the group consisting of a water-soluble polymeric compound, an inorganic colloid, an inorganic salt and an acid; the first coating liquid and the second coating liquid being simultaneously coated by means of steam as a carrier. This process can shorten the time for forming coating films of scale preventive agents to improve productivity, can improve the effect of preventing scales, can make colored particles less mix into polymer products obtained by this process, can lessen fish eyes and initial discoloring of formed products and can improve the quality of polymeric products and their formed or molded products.

  提供了一种通过在聚合容器中聚合具有乙烯双键的单体来生产聚合物的工艺。在该工艺中，聚合容器的内壁表面和聚合过程中单体接触的其他表面上有一层聚合物防垢涂膜。涂膜是通过涂覆第一涂覆液和第二涂覆液形成的，第一涂覆液含有一种选自具有 5 个或更多共轭 π 键的芳香族化合物和具有 5 个或更多共轭 π 键的杂环化合物的化合物，第二涂覆液含有至少一种选自水溶性高分子化合物、无机胶体、无机盐和酸的亲水性化合物；第一涂覆液和第二涂覆液通过蒸汽作为载体同时涂覆。这种工艺可以缩短防垢剂形成涂膜的时间以提高生产率，可以提高防垢效果，可以使有色颗粒较少地混入通过该工艺获得的聚合物产品中，可以减少成型产品的鱼眼和初始变色，可以提高聚合物产品及其成型或模塑产品的质量。

表征谱图