除虫菊素 | 121-21-1

• 物质功能分类: 化学农药原药 - 杀虫剂 - 拟除虫菊脂杀虫剂
• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 脂肪酰基
• 中文名称: 除虫菊素
• 中文别名: 除虫菊素I；除虫菊素Ⅰ
• 英文名称: pyrethrin I
• 英文别名: [(1S)-2-methyl-4-oxo-3-[(2Z)-penta-2,4-dienyl]cyclopent-2-en-1-yl] (1R,3R)-2,2-dimethyl-3-(2-methylprop-1-enyl)cyclopropane-1-carboxylate
• CAS: 121-21-1
• 化学式: C₂₁H₂₈O₃
• 分子量: 328.452
• InChiKey: ROVGZAWFACYCSP-VUMXUWRFSA-N

物化性质

• 比旋光度：
  D20 -14° (isooctane)
• 沸点：
  bp0.0005 146-150°
• 密度：
  1.5192
• 溶解度：
  氯仿（微溶）、乙酸乙酯（微溶）
• 颜色/状态：
  Viscous liquid
• 蒸汽压力：
  2.03X10-5 mm Hg at 25 °C
• 稳定性/保质期：
  Oxidizes readily and becomes inactive in air.
• 旋光度：
  Specific optical rotation: -14 deg at 20 °C/D (isooctane)
• 分解：
  When heated to decomp it emits acrid smoke and irritating fumes.
• 折光率：
  Index of refraction: 1.5242 at 20 °C/D

计算性质

• 辛醇/水分配系数(LogP)：
  5.4
• 重原子数：
  24
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  43.4
• 氢给体数：
  0
• 氢受体数：
  3

ADMET

代谢

拟除虫菊酯在体内被广泛代谢，粪便和尿液中母体化合物的残留物仅占10%。已鉴定出六种代谢物，并提出了两种主要的代谢途径，第一种涉及双键和/或甲基基团的氧化，第二种涉及酯键的水解。拟除虫菊酯I主要通过氧化过程代谢，而拟除虫菊酯II则通过水解和氧化过程的结合进行代谢。

Pyrethrins are extensively metabolized, the residues of the parent compound in feces and urine representing only 10%. Six metabolites were identified and two major metabolic pathways were suggested, the first involving oxidation of the double-bond and/or the methyl groups and the second involving hydrolysis of the ester bond. Pyrethrins I are metabolized mainly through oxidative processes, while pyrethrins II are metabolized through a combination of hydrolytic and oxidative processes.

来源:Hazardous Substances Data Bank (HSDB)

代谢

五组大鼠口服给予14C标记的拟除虫菊酯I，单次剂量为10 mg/kg体重（雄性和雌性），100 mg/kg体重（雄性）和50 mg/kg体重（雌性）。给予雌性的剂量较低，因为之前已经表明拟除虫菊提取物对雌性的毒性大于雄性。色谱分析表明，在所有剂量下，雄性和雌性尿液中代谢物的量态轮廓相似，并且粪便中所有存在的代谢物也都在尿液中出现。因此，使用高剂量雄性大鼠的尿液来通过重复注射复合尿液到半制备高效液相色谱仪上，并收集放射性标记的代谢物，以分离、纯化和鉴定主要代谢物。经过分离和纯化，通过化学操作和质谱分析鉴定出两种主要代谢物和四种次要代谢物。代谢物谱表明，在大鼠体内，拟除虫菊酯I通过两个主要代谢途径进行代谢：一是分子中环戊烯或环丙烷侧的双键氧化形成二醇，二是环丙烷环侧链上的甲基氧化形成羧酸。第二个途径涉及酯键的水解，形成相应的酸和醇。

Groups of five rats were given 14C-labelled pyrethrins I orally as a single dose of 10 mg/kg bw (males and females), 100 mg/kg bw (males), and 50 mg/kg bw (females). The dose administered to the females was lower because it had been shown previously that pyrethrum extract is more toxic to females than males. Chromatographic profiling indicated a quantitatively similar metabolic profile in urine in males and females at all doses and that all of the metabolites present in feces were also present in the urine. The urine from males at the high dose was therefore used to isolate, purify, and identify the major metabolites by repetitive injections of composited urine onto a semi-preparative high-performance liquid chromatograph and collection of radiolabelled metabolites. After isolation and purification, two major and four minor metabolites were identified by chemical manipulations and mass spectroscopy. The spectrum of metabolites indicated that in rats pyrethrins I are metabolized through two major metabolic pathways: oxidation of the double-bond on the cyclopentene or the cyclopropane side of the molecule to form a diol, and/or oxidation of the methyl groups on the side-chain of the cyclopropane ring to form a carboxylic acid. A second pathway involves hydrolysis of the ester bond to form the corresponding acid and alcohol.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在隔离和识别代谢物之后，确定了尿和粪便中代谢物的分布。在所有剂量下，尿液中的主要代谢物是菊花二羧酸。在粪便中，存在大量母化合物（在低剂量时小于10%），但另一种代谢物在所有剂量下最为普遍。这两种代谢物代表了超过三分之一的总放射性标记物被排泄。雄性和雌性大鼠以相似的方式代谢除虫菊素I，无论剂量如何，雄性和雌性之间的差异是数量上的，而不是质量上的。

After isolation and identification of the metabolites, the distribution of metabolites was determined in urine and feces. The major metabolite in urine at all doses was chrysanthemum dicarboxylic acid. In feces, a significant amount of parent compound was present (< 10% at the low dose), but another metabolite was the most prevalent at all doses. The two metabolites represented over one-third of the total excreted radiolabel. Male and female rats metabolized pyrethrins I in a similar manner, regardless of the dose, and the difference between males and females was quantitative rather than qualitative.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在给予大鼠口服(14)C-除虫菊素II 48小时之内，53%的(14)C以呼出的二氧化碳形式被回收，而在相同情况下，只有0.3%的(14)C-除虫菊素I以该形式被回收。从尿液中回收的(14)C.../是/46%...部分口服给药物质通过粪便排出，至少部分以代谢形式排出。已经从尿液中分离出三种化合物，并通过核磁共振和质谱鉴定。这三种化合物都是由...除虫菊素I和II产生的。这三种化合物都是酸和醇部分氧化的结果，分子的主要结构保持完整。

... Within 48 hr of oral admin of (14)C-pyrethrin II to rats, 53% of the (14)C was recovered as exhaled carbon dioxide, whereas only 0.3% of (14)C-pyrethrin I was recovered in that form under the same circumstances. The ... (14)C recovered from urine ... /was/ 46% ... some of the orally admin material is excreted in feces, at least partially in metabolized form. Three compounds have been isolated from urine & identified by NMR & mass spectra. All three are produced by ... pyrethrin I & II. All three are the result of oxidation of ... the acid & alcoholic moieties leaving the main structure of the molecule intact.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

癌症分类：有致癌性的提示性证据，但不足以评估对人类致癌的可能性/除虫菊酯/

Cancer Classification: Suggestive Evidence of Carcinogenicity but Not Sufficient to Assess Human Carcinogenic Potential /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

胡椒基丁醚通过抑制负责在节肢动物中代谢除虫菊酯的水解酶，从而增强除虫菊酯的杀虫活性。当胡椒基丁醚与除虫菊酯结合使用时，后者的杀虫活性可增加2到12倍。

Piperonyl butoxide potentiates /insecticidal activity/ of pyrethrins by inhibiting the hydrolytic enzymes responsible for pyrethrins' metabolism in arthropods. When piperonyl butoxide is combined with pyrethrins, the insecticidal activity of the latter drug is increased 2-12 times /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在1000 ppm杀虫剂和10000 ppm氧化胡椒基丁的饮食水平下...在大鼠肝细胞中/肥大、边缘化和细胞质包涵体/仅在8天内就得到了很好的发展，但是...并没有达到最大。变化与剂量成正比，并且与DDT产生的变化相似。这两种...的效果是叠加的。/杀虫剂/

At dietary level of 1000 ppm pyrethrins & 10000 ppm piperonyl butoxide ... /enlargement, margination, & cytoplasmic inclusions in liver cells of rats/ were well developed in only 8 days, but ... were not maximal. Changes were proportional to dosage & similar to those produced by DDT. Effects of the 2 ... were additive. /Pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

没有证据表明增效剂会增加拟除虫菊酯对哺乳动物的毒性。

There is no evidence that synergists incr toxicity of the pyrethrins to mammals. /pyrethrins/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

抗氧化剂用于帮助保护拟除虫菊酯残留，包括微量的焦儿茶酚、焦酚和氢醌；1-苯基偶氮-2-萘酚用于防止阳光的影响。

Antioxidants used to help protect insecticidal residues of pyrethrins include minute concn of pyrocatechol, pyrogallol, & hydroquinone; 1-benzene-azo-2-naphthol is used to protect against the effects of sunlight.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在摄入后，除虫菊酯会被胃肠道的各种消化酶水解。然而，一小部分具有杀虫活性的化合物或其衍生物会被吸收，这可以通过它们的毒性和对肝脏的影响来证明。

Following ingestion, the pyrethrins are hydrolysed by various digestive enzymes in the gastro-intestinal tract. However, a small portion of the insecticidally active compounds or their derivatives are absorbed as shown by their toxicity and their effect on the liver.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

拟除虫菊酯经口服给药后从胃肠道吸收。在给予雄性大鼠3毫克/公斤口服的实验中，几乎完全吸收并在100小时内代谢完毕。尿液中没有观察到拟除虫菊酯，尽管存在大量的代谢物。在粪便中，观察到少量的原形拟除虫菊酯，同样伴随着代谢物。

Pyrethrins are absorbed from the gastrointestinal tract following oral administration. Studies in male rats receiving 3 mg/kg orally resulted in almost complete absorption and metabolism within 100 hours. No pyrethrin was observed in urine, although substantial quantities of metabolites were present. In feces, small quantities of the parent pyrethrin were observed, again accompanied by metabolites.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

当动物接触到空气中释放的含有胡椒基丁氧基的除虫菊酯气溶胶时，这种混合物很少或没有系统性吸收。

Pyrethrins are absorbed through intact skin when applied topically. When animals were exposed to aerosols of pyrethrins with piperonyl butoxide being released into the air, little or none of the combination was systemically absorbed.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

大鼠对拟除虫菊酯I的吸收、分布和排泄进行了研究。口服给药后，超过90%的低剂量拟除虫菊酯I被吸收，血液中放射性标记物的浓度在5到8小时之间达到峰值。放射性标记残留物在分析的器官中广泛分布，以雌性脂肪中的浓度最高。...在雄性中，尿液中发现的管理放射性标记的平均百分比从32%到47%，在雌性中从50%到57%，其余通过粪便排出。

Absorption, distribution, and excretion in rats were investigated for pyrethrins I. After oral administration, more than 90% of a low dose of pyrethrins I was absorbed, and the concentration of radiolabel in blood peaked between 5 and 8 hr. The radiolabelled residues were widely distributed in the organs analyzed, with the highest concentrations in fat in females. ... The mean percentage of administered radiolabel found in the urine ranged from 32 to 47% in males and from 50 to 57% in females, the remainder being excreted in feces.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn,N
• 安全说明：
  S13,S60,S61
• 危险类别码：
  R20/21/22
• 海关编码：
  2918300011
• 危险品运输编号：
  UN 2902
• 包装等级：
  III
• 危险类别：
  6.1(b)

制备方法与用途

除虫菊素

除虫菊素是天然除虫菊提取物，具备杀虫药用价值。其内含多种成分，包括除虫菊酯Ⅰ、除虫菊酯Ⅱ、瓜菊酯和茉莉菊酯。

除虫菊素具有广谱杀虫作用，主要通过胃毒作用有效防治咀嚼式口器害虫；同时，还具备强烈的触杀作用，主要用于防控刺吸式口器害虫。它击倒速度快，对哺乳动物安全，易降解且不污染环境。

在20世纪40年代中期之前，化学合成农药如有机氯、有机磷和氨基酸甲酯类杀虫剂尚未问世时，除虫菊制剂就已广泛应用于农业害虫防治，并取得了显著效果。从1947年起，人工首次成功合成了拟除虫菊酯，目前已有人工合成的拟除虫菊酯类化合物包括：烯丙菊酯（1947年）、胺菊酯（1963年）、苄呋菊酯（1965年）、苯醚菊酯（1968年）、苄氯菊酯（1972年）、氯氰菊酯（1973年）和溴氰菊酯（1973年），以及非三碳环的杀灭菊酯等。这些合成物不仅药效、光稳定性超过天然除虫菊酯及有机磷、有机氯、氨基甲酸酯类常用合成杀虫剂，还逐步替代了天然物在室内和农业害虫防治中的应用。

图1展示了除虫菊素主要成分除虫菊酯Ⅰ和除虫菊酯Ⅱ的化学结构式。以上信息由Chemicalbook的晓楠编辑整理。

反应信息

• 作为反应物：
  描述：

  除虫菊素 在 乙醇 、 硫酸 、 2,4-二硝基苯肼 作用下， 生成 (Ξ)-4-ethoxy-3-methyl-2-penta-2c,4-dienyl-cyclopent-2-enone-(2,4-dinitro-phenylhydrazone)
  参考文献：
  名称：

  注2：4-二硝基苯肼法测定除虫菊

  摘要：

  描述的实验阐明了 DNP * 方法 1 用于除虫菊和丙烯菊酯测定的化学过程。在分析一些非杀虫污染物的过程中，已经确定了结果，并根据新发现审查了该方法的范围和局限性。

  DOI：

  10.1002/jsfa.2740071203
• 作为产物：
  描述：

  S-烯丙醇酮 在 [2-(1-methylethoxy-O)phenylmethyl-C](nitrato-O,O'){rel-(2R,5R,7R)-adamantane-2,1-diyl[3-(2,4,6-trimethylphenyl)-1-imidazolidinyl-2-ylidene]}ruthenium 、 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 四氢呋喃 为溶剂， 反应 13.0h， 生成 除虫菊素
  参考文献：
  名称：

  Synthesis of pyrethroids and pyrethroid-containing compositions

  摘要：

  本发明提供了合成拟除虫菊酯化合物的方法。该方法包括形成第一反应，其中包括烯烃和一种allethrolone型不饱和醇，在足以形成交换反应产物的条件下，并将交换反应产物转化为拟除虫菊酯化合物。本发明的方法可用于制备包括拟除虫菊酯I、辛林I、茉莉醇I、拟除虫菊酯II、辛林II和茉莉醇II以及其他合成拟除虫菊酯化合物的化合物。还描述了用于控制昆虫的杀虫剂组合物和方法。

  公开号：

  US09487471B1

文献信息

• [EN] ACC INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS DE L'ACC ET UTILISATIONS ASSOCIÉES
  申请人：GILEAD APOLLO LLC

  公开号：WO2017075056A1

  公开（公告）日：2017-05-04

  The present invention provides compounds I and II useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了化合物I和II，这些化合物可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及它们的组合物和使用方法。
• [EN] MICROBIOCIDAL OXADIAZOLE DERIVATIVES<br/>[FR] DÉRIVÉS D'OXADIAZOLE MICROBIOCIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2017157962A1

  公开（公告）日：2017-09-21

  Compounds of the formula (I) wherein the substituents are as defined in claim 1, useful as a pesticides, especially fungicides.

  式(I)的化合物，其中取代基如权利要求1所定义，作为杀虫剂特别是杀菌剂有用。
• Thieno-pyrimidine compounds having fungicidal activity
  申请人：Brewster Kirkland William

  公开号：US20070093498A1

  公开（公告）日：2007-04-26

  The present invention relates to thieno[2,3-d]-pyrimidine compounds having fungicidal activity.

  本发明涉及具有杀真菌活性的噻吩[2,3-d]-嘧啶化合物。
• [EN] INSECTICIDAL TRIAZINONE DERIVATIVES<br/>[FR] DÉRIVÉS DE TRIAZINONE INSECTICIDES
  申请人：SYNGENTA PARTICIPATIONS AG

  公开号：WO2013079350A1

  公开（公告）日：2013-06-06

  Compounds of the formula (I) or (I'), wherein the substituents are as defined in claim 1, are useful as pesticides.

  式(I)或(I')的化合物，其中取代基如权利要求1所定义的那样，可用作杀虫剂。
• TRIAZOLE ACC INHIBITORS AND USES THEREOF
  申请人：Gilead Apollo, LLC

  公开号：US20170166584A1

  公开（公告）日：2017-06-15

  The present invention provides triazole compounds useful as inhibitors of Acetyl CoA Carboxylase (ACC), compositions thereof, and methods of using the same.

  本发明提供了三唑化合物，可用作乙酰辅酶A羧化酶（ACC）的抑制剂，以及其组合物和使用方法。