Azaspiracid | 214899-21-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 氮杂螺癸烷衍生物
• 英文名称: Azaspiracid
• CAS: 214899-21-5
• 化学式: C₄₇H₇₁NO₁₂
• 分子量: 842.08
• InChiKey: AHFHSIVCLPAESC-SJVADWSCSA-N

物化性质

• 密度：
  1.27±0.1 g/cm3(Predicted)
• 颜色/状态：
  Colorless amorphorous solid

计算性质

• 辛醇/水分配系数(LogP)：
  3.7
• 重原子数：
  60
• 可旋转键数：
  9
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.85
• 拓扑面积：
  164
• 氢给体数：
  4
• 氢受体数：
  13

ADMET

毒理性

• 相互作用

AZ-4在静息细胞中并未改变细胞质Ca2+。然而，该毒素以剂量依赖性方式抑制了由多杀菌素（Tg）诱导的细胞质Ca2+水平升高。AZ-4减少了由Tg引起的Ca2+内流，但并未影响由该药物引起的内储存Ca2+的释放。AZ-4对Tg诱导的Ca2+内流的影响是可逆的，并且不受腺苷3',5'-环单磷酸（cAMP）途径的调节。当AZ-4在镍之前、之后或与其一同添加时，镍是一种非特异性的Ca2+通道阻断剂，其效果无法区分且是累加的。AZ-4还抑制了由岩沙海葵毒素（MTX）刺激的Ca2+内流，抑制率为5到10%。

... AZ-4 did not modify cytosolic Ca2+ in resting cells. However, the toxin dose-dependent inhibited the increase in cytosolic Ca2+ levels induced by thapsigargin (Tg). AZ-4 decreased Ca2+-influx induced by Tg but did not affect the Ca2+-release from internal stores induced by this drug. The effects of AZ-4 on Ca2+-influx induced by Tg were reversible and not regulated by adenosine 3',5'-cyclic monophosphate (cAMP) pathway. When AZ-4 was added before, after or together with nickel, an unspecific blocker of Ca2+ channels, the effects were indistinguishable and additive. AZ-4 also inhibited maitotoxin (MTX)-stimulated Ca2+-influx by 5 to 10%.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

基本治疗：建立专利气道（如需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。密切观察呼吸不足的迹象，并在需要时辅助通气。通过非循环呼吸面罩以10至15升/分钟的速度给予氧气。监测肺水肿，并在必要时进行治疗……。监测休克，并在必要时进行治疗……。预防癫痫发作，并在必要时进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在转运过程中，用0.9%的生理盐水（NS）连续冲洗每只眼睛……。不要使用催吐剂。对于摄入，如果患者能吞咽、有强烈的干呕反射且不流口水，则用温水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污染后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒物A和B/

Basic treatment: Establish a patent airway (oropharyngeal or nasopharyngeal airway, if needed). Suction if necessary. Watch for signs of respiratory insufficiency and assist ventilations if needed. Administer oxygen by nonrebreather mask at 10 to 15 L/min. Monitor for pulmonary edema and treat if necessary ... . Monitor for shock and treat if necessary ... . Anticipate seizures and treat if necessary ... . For eye contamination, flush eyes immediately with water. Irrigate each eye continuously with 0.9% saline (NS) during transport ... . Do not use emetics. For ingestion, rinse mouth and administer 5 ml/kg up to 200 ml of water for dilution if the patient can swallow, has a strong gag reflex, and does not drool ... . Cover skin burns with dry sterile dressings after decontamination ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

高级治疗：对于昏迷的患者、严重肺水肿的患者或严重呼吸窘迫的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用带气囊的面罩进行正压通气技术可能有益。考虑对肺水肿进行药物治疗...。对于严重的支气管痉挛，考虑给予β激动剂，如沙丁胺醇...。监测心率和必要时治疗心律失常...。开始静脉输注D5W/SRP：“保持开放”，最小流量/。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格液。对于伴有低血容量迹象的低血压，谨慎给予液体。注意液体过载的迹象...。用地西泮或劳拉西泮治疗癫痫...。使用丙美卡因氢氯化物协助眼部冲洗...。/毒物A和B/

Advanced treatment: Consider orotracheal or nasotracheal intubation for airway control in the patient who is unconscious, has severe pulmonary edema, or is in severe respiratory distress. Positive-pressure ventilation techniques with a bag valve mask device may be beneficial. Consider drug therapy for pulmonary edema ... . Consider administering a beta agonist such as albuterol for severe bronchospasm ... . Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start IV administration of D5W /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's if signs of hypovolemia are present. For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam or lorazepam ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

大多数病例都是轻微且自限性的，不需要特殊治疗...保持呼吸道通畅，必要时协助通气。用静脉晶体液替换胃肠炎引起的液体和电解质丢失。/食物中毒：鱼和贝类/

Most cases are mild and self-limited and require no specific treatment ... Maintain an open airway and assist ventilation if necessary. Replace fluid and electrolyte losses from gastroenteritis with intravenous crystalloid fluids. /Food poisoning: fish and shellfish/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 人类毒性摘录

症状和体征：腹泻性贝类中毒会引起恶心、呕吐、胃痛和严重腹泻。/食物中毒：鱼和贝类/

/SIGNS AND SYMPTOMS/ Diarrhetic shellfish poisoning causes nausea, vomiting, stomach cramps, and severe diarrhea. /Food poisoning: Fish and Shellfish/

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

阿扎斯皮酸（AZA1）及其甲基化和去甲基化类似物AZA2和AZA3分别在贝类组织中分布。

... azaspiracid (AZA1) and its methyl- and demethyl- analogues, AZA2 and AZA3 respectively, are distributed throughout shellfish tissues.

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为产物：
  描述：

  在 lithium hydroxide 作用下， 以 甲醇 、 水 为溶剂， 反应 16.0h， 以45%的产率得到Azaspiracid
  参考文献：
  名称：

  拟议的azaspiracid-1结构的全合成，第2部分：C1-C20，C21-C27和C28-C40片段的偶联和合成完成。

  摘要：

  DOI：

  10.1002/anie.200351826

文献信息

• Total Synthesis of the Proposed Azaspiracid-1 Structure, Part 2: Coupling of the C1–C20, C21–C27, and C28–C40 Fragments and Completion of the Synthesis
  作者：K. C. Nicolaou、David Y.-K. Chen、Yiwei Li、Wenyuan Qian、Taotao Ling、Stepan Vyskocil、Theocharis V. Koftis、Mugesh Govindasamy、Noriaki Uesaka

  DOI：10.1002/anie.200351826

  日期：2003.8.11