(+)-毒蕈碱氯化物 | 2303-35-7

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: (+)-毒蕈碱氯化物
• 中文别名: （+）-氯卡斯汀
• 英文名称: (+)-muscarine chloride
• 英文别名: muscarine；Muscarine chloride；[(2S,4R,5S)-4-hydroxy-5-methyloxolan-2-yl]methyl-trimethylazanium;chloride
• CAS: 2303-35-7
• 化学式: C₉H₂₀NO₂*Cl
• 分子量: 209.716
• InChiKey: WUFRNEJYZWHXLC-CTERPIQNSA-M

物化性质

• 熔点：
  180-181 °C
• 溶解度：
  H2O:50 mg/mL
• 颜色/状态：
  STOUT PRISMS FROM ETHANOL + ACETONE
• 稳定性/保质期：
  AQUEOUS SOLUTIONS ARE STABLE
• 旋光度：
  SPECIFIC OPTICAL ROTATION: +8.1 DEG @ 25 °C/D (CONCN= 3.5 IN ETHANOL)

计算性质

• 辛醇/水分配系数(LogP)：
  -2.77
• 重原子数：
  13
• 可旋转键数：
  2
• 环数：
  1.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  3

ADMET

毒理性

• 副作用

神经毒素 - 其他中枢神经系统神经毒素

Neurotoxin - Other CNS neurotoxin

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

毒理性

• 人类毒性摘录

至少有3种临床中毒类型可以由毒鹅膏属物种引起。快速型（神经性蘑菇中毒）在食用毒蝇伞或豹斑鹅膏后发生。症状在几分钟或几小时内出现，可能或可能不是由于生物碱毒蝇碱引起。效果模仿...副交感神经系统的刺激。结果是腹痛、视力模糊和低血压。/鹅膏毒素/

AT LEAST 3 TYPES OF CLINICAL POISONINGS CAN BE INDUCED BY TOXIC SPECIES OF AMANITA. A RAPID TYPE (MYCETISMUS NERVOSA) FOLLOWS INGESTION OF A MUSCARIA OR A PANTHERINA. SYMPTOMS OCCUR WITHIN FEW MIN OR A FEW HR & MAY OR MAY NOT BE DUE TO ALKALOID MUSCARINE. EFFECTS MIMIC...STIMULATION OF PARASYMPATHETIC NERVOUS SYSTEM. RESULT IS COLICKY ABDOMINAL PAIN...BLURRED VISION...& HYPOTENSION. /AMANITA TOXINS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

摄入可能导致...出汗...瞳孔缩小，心动过缓，循环衰竭。可能会进展到抽搐，昏迷，几小时内死亡。/毒蕈碱/

INGESTION MAY CAUSE...DIAPHORESIS...MIOSIS, BRADYCARDIA, CIRCULATORY COLLAPSE. MAY PROGRESS TO CONVULSIONS, COMA & DEATH IN A FEW HOURS. /MUSCARINE/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

26名儿童食用了不同种类的蘑菇后神经学和脑电图检查结果讨论。在摄入鹅膏菌后，建议将脑病作为间接并发症。在肝功能完全衰竭的病例中可以看到。新发现是脑电图在摄入粉红褶伞菌的儿童中的表现。在3名接受调查的儿童中，脑电图显示出明显的弥漫性异常。在临床上，只有1名儿童表现出典型的毒蝇碱中毒症状和体征，而另外2名儿童则表现出昏昏欲睡和混乱，并表现出四肢肌肉的抽搐。粉红褶伞菌除了含有毒蝇碱外，还含有直接影响大脑功能的毒素。食用毒蝇伞的儿童的脑电图正常，临床表现为胆碱能刺激的症状和体征。个别蘑菇种类的毒性和个别儿童对种类的敏感性和反应性各不相同，取决于多种因素。

RESULTS OF NEUROLOGICAL AND EEG EXAMINATIONS IN 26 CHILDREN INTOXICATED WITH MUSHROOMS OF VARIOUS SPECIES ARE DISCUSSED. ENCEPHALOPATHY, DEVELOPED FOLLOWING INGESTION OF AMANITA PHALLOIDES, IS SUGGESTED AS AN INDIRECT COMPLICATION. IT WAS SEEN IN CASES OF COMPLETE FAILURE OF LIVER FUNCTION. A NEW FINDING IS THAT OF THE EEG PICTURE IN CHILDREN INTOXICATED WITH INOCYBE PATOUILLARDI. IN EACH OF 3 CHILDREN INVESTIGATED, EEG DEMONSTRATED PRONOUNCED DIFFUSE ABNORMALITIES. CLINICALLY, ONLY 1 CHILD DEMONSTRATED SYMPTOMS & SIGNS TYPICAL OF MUSCARINE INTOXICATION, WHILE THE REMAINING 2 WERE DROWSY & CONFUSED & EXHIBITED TWITCHING OF EXTREMITY MUSCLES. INOCYBE PATOUILLARDI CONTAINS, IN ADDITION TO MUSCARINE, TOXINS WITH A DIRECT EFFECT ON CEREBRAL FUNCTION. CHILDREN INTOXICATED WITH AMANITA MUSCARIA HAD NORMAL EEG & CLINICAL SYMPTOMS & SIGNS OF CHOLINERGIC STIMULATION. TOXICITY OF INDIVIDUAL MUSHROOM SPECIES & SENSITIVITY & REACTIVITY OF INDIVIDUAL CHILDREN TO SPECIES VARIED & DEPENDED ON A NUMBER OF FACTORS.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

在给予不同物种极其微小剂量的毒蕈碱（0.01-0.03微克/千克）静脉注射后...出现了明显的血压下降和心脏跳动减慢或暂时停止。/毒蕈碱/

...FOLLOWING IV INJECTION OF EXTREMELY SMALL DOSES (0.01-0.03 UG/KG) OF MUSCARINE IN VARIOUS SPECIES...MARKED FALL IN BLOOD PRESSURE & SLOWING OR TEMPORARY CESSATION OF THE HEART /OCCURRED/. /MUSCARINE/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

非常差地被吸收来自胃肠道... /毒蕈碱/

...VERY POORLY ABSORBED FROM GI TRACT... /MUSCARINE/

来源:Hazardous Substances Data Bank (HSDB)

制备方法与用途

类别：有毒物品

• 毒性分级：剧毒
• 急性毒性：静脉-小鼠 LD50: 0.23毫克/公斤
• 可燃性危险特性：可燃，火场排出含氮氧化物和氯化物辛辣刺激烟雾
• 储运特性：库房通风低温干燥；与酸类、食品分开储运
• 灭火剂：水、砂土

反应信息

• 作为反应物：
  描述：

  (+)-毒蕈碱氯化物 在 磷化氢 、 氢碘酸 作用下， 生成 trimethyl-((2S)-5t-methyl-(2rH)-tetrahydro-furfuryl)-ammonium; tetrachloroaurate (III)
  参考文献：
  名称：

  Koegl et al., Recueil des Travaux Chimiques des Pays-Bas, 1957, vol. 76, p. 109,126

  摘要：

  DOI：
• 作为产物：
  描述：

  2,5-anhydro-4,5-di-O-benzoyl-D-glucitol 在 chromium dichloride 、 四氯化碳 、 sodium tetrahydroborate 、 偶氮二异丁腈 、 三正丁基氢锡 、 三苯基膦 、 pyridinium chlorochromate 作用下， 以 甲醇 、 水 、 丙酮 、 乙腈 、 苯 为溶剂， 生成 (+)-毒蕈碱氯化物
  参考文献：
  名称：

  （+）-毒蕈碱的简单立体定向合成

  摘要：

  描述了由-甘露糖醇经由2，5-脱水-葡萄糖醇的毒性原理（+）-毒蕈碱的高产率立体定向合成。

  DOI：

  10.1016/s0040-4039(00)93174-5

文献信息

• Total synthesis of the muscarines
  作者：Michael C. Pirrung、Carl V. DeAmicis

  DOI：10.1016/s0040-4039(00)80041-6

  日期：1988.1

  The total syntheses of racemic muscarine and allo-muscarine have been achieved using as a key step the stereospecific photochemical ring expansion of a cyclobutanone.

  外消旋毒蕈碱的和全合成同种异体-muscarine已经使用作为密钥工序的环丁酮的立体有择光化学环扩展来实现的。
• Synthesis of (2R,3S)-1,2,3-Butanetriol Derivatives From (R)-2,3-O-Isopropylideneglyceraldehyde and of the (2S,3R)-Enantiomers FromD-Glucose. Application to the Synthesis of Enantiomerically Pure Muscarine
  作者：Johann Mulzer、Alfred Angermann、Winfried Münch、Günter Schlichthörl、Angelo Hentzschel

  DOI：10.1002/jlac.198719870103

  日期：1987.1.31

  Both enantiomers of the O-protected epoxy alcohol derivative 1b have been prepared from (R)-2,3-O-isopropylideneglyceraldehyde and D-glucose, respectively, and utilized in a practical synthesis of L- and D-muscarine iodide and chloride.

  O-保护的环氧醇衍生物1b的两种对映体分别由（R）-2，3 - O-异亚丙基甘油醛和D-葡萄糖制备，并用于L-和D-穆斯卡因碘化物和氯化物的实际合成中。
• Diastereoselectivity in the Synthesis of 3(2H)-Furanones. Total Synthesis of (+)-Muscarine
  作者：Julian Adams、Marc-André Poupart、Louis Grenier

  DOI：10.1016/s0040-4039(00)99571-6

  日期：——

  The carbenoid cyclization reaction to form disubstituted 2,5-3(2H)-furanones exhibited a stereoselection favoring the cis isomers. This phenomenon was exploited in an enantioselective synthesis of (+)-muscarine.

  形成二取代的2,5-3（2H）-呋喃酮的类胡萝卜素环化反应显示出有利于顺式异构体的立体选择。该现象被用于（+）-毒蕈碱的对映选择性合成中。
• Multi-Layer Tablets and Bioadhesive Dosage Forms
  申请人：Nangia Avinash

  公开号：US20080311191A1

  公开（公告）日：2008-12-18

  Bioadhesives coatings increase the gastrointestinal retention time of orally-ingested medicaments. Certain bioadhesive coatings producing a fracture strength of at least 100 N/m 2 , as measured on rat intestine, when applied to at least one surface of a pharmaceutical dosage form for oral delivery of a drug, result in a gastrointestinal retention time of at least 4 hours in a fed beagle dog model, during which the drug is released from the dosage form. Multi-layer tablets, particularly those including hydrophobic excipients, are useful in administering hygroscopic and/or deliquescent drugs. In addition, varying the amount of drug in multi-layer tablets allows the release rate of the drug to be controlled.

  生物粘合剂涂层可以增加口服药物的胃肠道保留时间。当应用于至少一种药物剂型的表面以口服给药时，产生至少100 N/m²的断裂强度的某些生物粘合剂涂层（在大鼠肠道上测量）可导致在饲养的比格犬模型中至少保留4小时的胃肠道保留时间，在此期间药物从剂型中释放。多层片剂，特别是包括疏水助剂的多层片剂，可用于给予吸湿性和/或易溶性药物。此外，改变多层片剂中药物的量可以控制药物的释放速率。
• A simple, stereospecific synthesis of dl-muscarine and dl-allomuscarine
  作者：T. Matsumoto、A. Ichihara、N. Ito

  DOI：10.1016/s0040-4020(01)83096-9

  日期：——

  A bromolactone (VII) was stereospecifically converted to a tetrabydrofuran (IVa, Me/CO2H cis) and a dimethylamide (VIII, Me/CONMe2 trans. Possible mechanisms for these reactions are discussed. Since IVa and VIII have been transformed to dl-muscarine (I) and dl-allomuscarine (II) respectively, stereospecific formation of IVa and VIII provides a stereospecific synthesis of these muscarines.

  将溴内酯（VII）立体定向转化为四氢呋喃（IVa，Me / CO 2 H cis）和二甲基酰胺（VIII，Me / CONMe 2 trans），讨论了这些反应的可能机理，因为IVa和VIII已转化为dl -毒蕈碱（I）和dl-铝肉碱（II），IVa和VIII的立体定向形成提供了这些毒蕈碱的立体定向合成。