(+)-oxypeucedanin | 3173-02-2

• 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
• 英文名称: (+)-oxypeucedanin
• 英文别名: Oxypeucedanin；4-[[(2R)-3,3-dimethyloxiran-2-yl]methoxy]furo[3,2-g]chromen-7-one
• CAS: 3173-02-2
• 化学式: C₁₆H₁₄O₅
• 分子量: 286.284
• InChiKey: QTAGQHZOLRFCBU-CYBMUJFWSA-N

物化性质

• 熔点：
  104-105 °C(Solv: ethyl ether (60-29-7); chloroform (67-66-3))
• 沸点：
  469.5±45.0 °C(Predicted)
• 密度：
  1.320±0.06 g/cm3(Predicted)
• 颜色/状态：
  Pale yellow crystals
• 溶解度：
  In water, 97.9 mg/L at 25 °C (est)
• 蒸汽压力：
  7.13X10-8 mm Hg at 25 °C (est)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  61.2
• 氢给体数：
  0
• 氢受体数：
  5

ADMET

毒理性

• 毒性总结

鉴定和使用：(+)-氧化白芷素是白芷（Peucedanum ostruthium (L) Koch）的一个组成部分，白芷在奥地利的高山地区传统上被用作利口酒和苦味酒的成分，也作为草药药物。它已经被测试为实验性治疗。人体研究：在体外测试时，它显示出适度的保肝活性。动物研究：在大鼠中测试时并未显示出肝毒性。口服氧化白芷素后，在2周大的小鸡中产生了光敏性。2周大的小鸡和2周大的火鸡雏鸡分别被喂食0.4%、0.8%和1.6%体重的大花金挖耳（C. watsonii）种子或全株，或者是长脚金挖耳（C. longipes）的种子，然后每天在阳光下放置5小时，持续7天。所有植物材料都在小鸡中产生了中到重度光敏性。毒性症状包括畏光；喙、鸡冠和脚的红色变色；眼周区域的羽毛脱落；鸡冠和喙边缘的干性浆液性分泌物；角膜结膜炎；以及脚和腿上的多个病变。火鸡雏鸡表现出与小鸡相似的症状。喂食长脚金挖耳种子的火鸡的死亡率特别高。治疗6周后火鸡的毒性症状包括腿部的震颤；上喙的上翻和缩短；以及脚趾的缩短、变形和坏疽。

IDENTIFICATION AND USE: (+)-Oxypeucedanin is a component of Peucedanum ostruthium (L) Koch (masterwort), traditionally used in the alpine region of Austria as an ingredient of liqueurs and bitters and as a herbal drug. It has been tested as experimental therapy. HUMAN STUDIES: It demonstrated moderate hepatoprotective activity when tested in vitro. ANIMAL STUDIES: It was not hepatotoxic when tested in rats. Oxypeucedanin administered orally, produced photosensitivity in 2 wk old chicks. Two week old chicks and 2 wk old turkey poults were fed seed or whole plants of C. watsonii or seed of C. longipes at 0.4, 0.8 and 1.6% of body wt, and then placed in sunlight for 5 hr each day for 7 days. All plant material produced moderate to severe photosensitivity in chicks. Toxic signs included photophobia; red discoloration of beak, comb and feet; loss of feathers in the periorbital area; dried serous fluid on the comb and edge of the beak; keratoconjunctivitis; and multiple lesions on feet and legs. Turkey poults showed a syndrome similar to that of chicks. Mortality was particularly high in turkeys fed C. longipes seed. Toxic signs in turkeys 6 wk after treatment included tremors in the legs; upturning and shortening of the upper beak; and shortening, disfigurement and gangrene of the toes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

这项研究旨在探究一系列天然香豆素类化合物（自然发生的呋喃香豆素，NOFs），包括异欧前胡素、欧前胡素、(+)-氧化补骨脂素、(+)-白当归素和(+)-白当归素内酯，对由致癌物[ furylfuramide（呋喃甲酰胺）和N-甲基-N'-硝基-N-亚硝基胍]以及前致癌物2-[2-(乙酰氨基)-4-氨基-5-甲氧基苯基]-5-氨基-7-溴-4-氯-2H-苯并三唑(PBTA-4)和2-氨基-3,4-二甲基-3H-咪唑[4,5-f]喹啉(MeIQ)]通过umu测试（基于SOS反应）诱导的大鼠S9或大鼠和人重组细胞色素P450 (CYP) 1As催化的遗传毒性代谢物的影响。在人类饮食中发现的这五种不同的NOFs，强烈抑制了前致癌物诱导的umuC基因表达，但并未受到致癌物的影响。值得注意的是，异欧前胡素和(+)-白当归素被发现对大鼠和人CYP1A1或大鼠和人CYP1A2催化的PBTA-4和MeIQ到遗传毒性代谢物的代谢激活具有显著的抑制作用。此外，为了阐明这些NOFs对抗前致癌物的作用机制，还研究了它们对大鼠和人CYP1A1或大鼠和人CYP1A2相关酶活性7-乙氧基补骨脂素-O-脱乙基酶（EROD）的影响。发现一些NOFs以0.23-20.64 uM的IC(50)值降低EROD活性，这是由于对CYP1A1和CYP1A2依赖的单加氧酶的强烈抑制。进一步地，通过Dixon图和Cornish-Bowden图分析了NOFs对人类CYP1A1和CYP1A2的抑制机制。抑制类型的动力学研究表明，这些化合物以多种方式而非单一方式抑制人类CYP1A1和CYP1A2。此外，两阶段孵育实验表明，除了欧前胡素之外，NOFs以机制为基础的方式抑制人类CYP1A1，但直接抑制人类CYP1A2。这些数据表明，人类饮食中暴露的某些NOFs可能通过抑制CYP1A1和CYP1A2酶来影响前致癌物的代谢激活。

This study was designed to investigate the antigenotoxic effects of a series of naturally occurring furanocoumarins (NOFs) including isoimperatorin, imperatorin, (+)-oxypeucedanin, (+)-byakangelicol, and (+)-byakangelicine on antigenotoxic activities against genotoxicity induced by carcinogens [furylfuramide and N-methyl-N'-nitro-N-nitrosoguanidine], and procarcinogens 2-[2-(acetylamino)-4-amino-5-methoxyphenyl]-5-amino-7-bromo-4-chloro-2H-benzotriazole (PBTA-4) and 2-amino-3,4-dimethyl-3H-imidazo-[4,5-f] quinoline (MeIQ)] to genotoxic metabolites catalyzed by rat S9 or rat and human recombinant cytochrome P450 (CYP) 1As by using the umu test based on SOS response. Five different NOFs, which were found in the human diets, strongly inhibited the umuC induction by procarcinogens, but /was not/ affected by carcinogens. Notably, isoimperatorin and (+)-byakangelicol were found to be potent inhibitors on the metabolic activation of PBTA-4 and MeIQ to genotoxic metabolites catalyzed by rat and human CYP1A1, or rat and human CYP1A2, respectively. In addition, to elucidate the mechanism of their antigenotoxic effects against procarcinogens, the effects of NOFs on rat and human CYP1A1- or rat and human CYP1A2-related enzyme activities of 7-ethoxyresorufin-O-deethylase (EROD) were also investigated. Reduction of the EROD activities by some of the NOFs with IC(50) values of 0.23-20.64 uM was found to be due to strong inhibition of CYP1A1 and CYP1A2 dependent monooxygenases. Furthermore, the mechanism of inhibitions by NOFs on human CYP1A1 and CYP1A2 was analyzed by means of Dixon plots plus Cornish-Bowden plots. The kinetic studies of inhibition types revealed that these compounds inhibited the human CYP1A1 and CYP1A2 a variety of modes rather than by a uniform one. Moreover, experiments with a two-stage incubation indicated that NOFs, except for imperatorin, inhibited human CYP1A1 in a mechanism-based manner, but directly inhibited human CYP1A2. This data suggests that certain NOFs, to which humans are exposed in the diet, may be capable of affecting the metabolic activation of procarcinogens due to inhibitions of CYP1A1 and CYP1A2 enzymes.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 立即急救：确保已经进行了充分的中毒物清除。如果患者停止呼吸，开始人工呼吸，最好使用需求阀复苏器、袋阀面罩装置或口袋面罩，按训练操作。如有必要，执行心肺复苏。立即用缓慢流动的水冲洗受污染的眼睛。不要催吐。如果发生呕吐，让患者前倾或置于左侧卧位（如果可能的话，头部向下）以保持呼吸道畅通，防止吸入性肺炎。保持患者安静，维持正常体温。寻求医疗救助。 /毒物A和B/

/SRP:/ Immediate first aid: Ensure that adequate decontamination has been carried out. If patient is not breathing, start artificial respiration, preferably with a demand valve resuscitator, bag-valve-mask device, or pocket mask, as trained. Perform CPR if necessary. Immediately flush contaminated eyes with gently flowing water. Do not induce vomiting. If vomiting occurs, lean patient forward or place on left side (head-down position, if possible) to maintain an open airway and prevent aspiration. Keep patient quiet and maintain normal body temperature. Obtain medical attention. /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 基本治疗：建立专利气道（如有需要，使用口咽或鼻咽气道）。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，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，如有必要，进行治疗……。监测休克，如有必要，进行治疗……。预防癫痫发作，如有必要，进行治疗……。对于眼睛污染，立即用水冲洗眼睛。在运输过程中，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，如果患者能够吞咽、有强烈的呕吐反射且不流口水，则用水冲洗口腔，并给予5毫升/千克，最多200毫升的水进行稀释……。在去污后，用干燥的无菌敷料覆盖皮肤烧伤……。/毒药A和B/

/SRP:/ 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

/SRP:/ 高级治疗：对于失去意识、严重肺水肿或严重呼吸困难的病人，考虑进行口咽或鼻咽插管以控制气道。使用带气囊的面罩进行正压通气可能有帮助。考虑使用药物治疗肺水肿……。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5%葡萄糖溶液（D5W），保持通道开放，最低流量/ SRP: "保持开放"，最低流量。如果出现低血容量的迹象，使用0.9%生理盐水（NS）或乳酸钠林格氏液（LR）。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……。使用地西泮（安定）或劳拉西泮（阿提凡）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/

/SRP:/ 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 TKO /SRP: "To keep open", minimal flow rate/. Use 0.9% saline (NS) or lactated Ringer's (LR) 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 (Valium) or lorazepam (Ativan) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poisons A and B/

来源:Hazardous Substances Data Bank (HSDB)

反应信息

• 作为反应物：
  描述：

  (+)-oxypeucedanin 在 盐酸 作用下， 反应 3.0h， 生成 4-((R)-3-Methoxy-3-methyl-2-trimethylsilanyloxy-butoxy)-furo[3,2-g]chromen-7-one
  参考文献：
  名称：

  通过高速逆流色谱分离商业石灰和葡萄柚油的非挥发物。

  摘要：

  通过高速逆流色谱法（HS-CCC）分离Key和波斯石灰的冷压果皮油的非挥发性馏分以及葡萄柚。除了分离主要香豆素，补骨脂素和聚甲氧基黄酮，还富集了许多次要成分，并通过GC-MS和HPLC-UV对其进行了成功表征。确定5,7,8-三甲氧基香豆素和水合氧化金丝桃宁与柠檬醛的环状缩醛为石灰油的新的非挥发性痕量成分，并通过NMR光谱法确认。柠檬酸氧杂二十二烷基乙缩醛特别是在A型键石灰油中发现，由于汁液与油的接触，在工业加工过程中暴露于酸性条件下。一些已确认的次要成分，例如青花烯酚，异氧哌丁宁，

  DOI：

  10.1021/jf052267t