(2S,3R,10S)-3,13-dihydroxy-2-[(1R)-1-hydroxyheptyl]-10-[(S)-hydroxy-[(2S)-6-oxo-2,3-dihydropyran-2-yl]methyl]-6,14-dioxatricyclo[10.3.0.04,8]pentadeca-1(12),4(8)-diene-5,7,15-trione | 22467-31-8

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 羧酸及其衍生物
• 英文名称: (2S,3R,10S)-3,13-dihydroxy-2-[(1R)-1-hydroxyheptyl]-10-[(S)-hydroxy-[(2S)-6-oxo-2,3-dihydropyran-2-yl]methyl]-6,14-dioxatricyclo[10.3.0.04,8]pentadeca-1(12),4(8)-diene-5,7,15-trione
• CAS: 22467-31-8
• 化学式: C₂₆H₃₂O₁₁
• 分子量: 520.5
• InChiKey: XOEFANNJIKAWGX-RRIJHKHGSA-N

物化性质

• 熔点：
  210-214℃ (decomposition)
• 溶解度：
  乙腈：可溶；二甲基亚砜：可溶
• 颜色/状态：
  NEEDLES FROM ETHYL ACETATE
• 稳定性/保质期：
  STABLE AT ROOM TEMP /RUBRATOXINS/
• 旋光度：
  Specific optical rotation: +84 deg (acetone, 20 °C, c=2)

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  177
• 氢给体数：
  4
• 氢受体数：
  11

ADMET

代谢

除了完成葡萄糖到二氧化碳和水的氧化过程外，三羧酸循环还提供了生物合成一些次级代谢产物的中间体，包括rubratoxins...第一步涉及癸酸与草酰乙酸的缩合，这种方式类似于柠檬酸的形成。随后的脱水、脱羧和氧化导致形成一个中间酐，该酐二聚化，在进一步氧化后形成rubratoxin A。氧气功能是在哪个阶段引入的尚不清楚，特别是，这样的假设将意味着α,β-不饱和γ-内酯的羧基来源于乙酸的甲基碳。

AS WELL AS SERVING TO COMPLETE THE OXIDATION OF GLUCOSE TO CO2 & WATER, THE TRICARBOXYLIC ACID CYCLE ALSO PROVIDES INTERMEDIATES FOR THE BIOSYNTHESIS OF SOME SECONDARY METABOLITES, INCL THE RUBRATOXINS... THE FIRST STEP INVOLVES CONDENSATION OF DECANOIC ACID WITH OXALOACETIC ACID IN A MANNER ANALOGOUS TO THE FORMATION OF CITRIC ACID. SUBSEQUENT DEHYDRATION, DECARBOXYLATION & OXIDATION LEAD TO AN INTERMEDIATE ANHYDRIDE WHICH DIMERIZES TO FORM, AFTER FURTHER OXIDATION, RUBRATOXIN A. AT WHAT STAGE THE OXYGEN FUNCTIONS ARE INTRODUCED IS NOT CLEAR, &, IN PARTICULAR, SUCH A HYPOTHESIS WOULD MEAN THAT THE CARBOXYL GROUP OF THE ALPHA,BETA-UNSATURATED GAMMA-LACTONE WOULD BE DERIVED FROM THE METHYL CARBON OF ACETATE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

RUBRATOXIN A 作为次要代谢物出现，与RUBRATOXIN B（来自红青霉和紫色链霉菌的主要代谢物）一起出现。

RUBRATOXIN A OCCURS AS THE MINOR METABOLITE ALONG WITH RUBRATOXIN B, THE MAJOR METABOLITE FROM.../PENICILLIUM RUBRUM & P PURPUROGENUM/.

来源:Hazardous Substances Data Bank (HSDB)

代谢

一种无菌的葡萄糖-矿物质盐肉汤被接种了红色青霉的孢子悬浮液或菌丝球，并在静止状态下培养了14天。通过醚提取培养滤液并经薄层色谱法解析，回收了红毒素。丙二酸盐能增强毒素形成，但乙基丙二酸盐、莽草酸、醋酸盐以及异柠檬酸或草酸乙酯在丙二酸盐存在下添加时，对毒素形成的影响不大。当单独或与丙二酸盐联合存在于培养基中时，柠檬酸盐、顺式乌头酸、α-酮戊二酸盐、琥珀酸盐、延胡索酸盐和丙二酸盐会导致红毒素形成量减少15-50%。乙酰辅酶A（10-15摩尔/瓶）使毒素产量增加了80%。在10^-3摩尔浓度下，柠檬酸盐能将红毒素A的产量刺激多达100%。超过10^-3摩尔时，柠檬酸盐会抑制毒素的产生。丙二酸盐和延胡索酸盐+丙二酸盐能增强(2-14)C-醋酸盐掺入红毒素。丙酮酸盐+丙二酸盐使(2-14)C-醋酸盐掺入红毒素的量增加了40%。琥珀酸盐或α-酮戊二酸盐与丙二酸盐联合使用，导致标记醋酸盐掺入量的最高减少（36%）。

A STERILE GLUCOSE-MINERAL SALTS BROTH WAS INOCULATED WITH SPORE SUSPENSIONS OR MYCELIAL PELLETS OF PENICILLIUM RUBRUM AND INCUBATED QUIESCENTLY FOR 14 DAYS. RUBRATOXINS WERE RECOVERED FROM CULTURE FILTRATES BY ETHER EXTRACTION AND RESOLVED BY TLC. TOXIN FORMATION WAS ENHANCED BY MALONATE BUT WAS NOT MARKEDLY AFFECTED BY ETHYL MALONATE, SHIKIMATE, AND ACETATE OR BY ISOCITRATE OR OXALOACETATE ADDED IN THE PRESENCE OF MALONATE. CITRATE, CIS-ACONITATE, ALPHA-KETOGLUTARATE, SUCCINATE, FUMARATE AND MALONATE WHEN PRESENT IN THE MEDIUM ALONE OR IN CONJUNCTION WITH MALONATE CAUSED A 15-50% REDUCTION IN RUBRATOXIN FORMATION. ACETYL-COA (10-15 MOL/FLAS) CAUSED AN 80% INCREASE IN TOXIN YIELD. AT 10-3 MOLAR, CITRATE STIMULATED RUBRATOXIN A PRODUCTION BY AS MUCH AS 100%. ABOVE 10-3 MOLAR, CITRATE INHIBITED TOXIN PRODUCTION. INCORPORATION OF (2-14)C-ACETATE INTO RUBRATOXIN WAS ENHANCED BY MALONATE AND FUMARATE + MALONATE. PYRUVATE + MALONATE PRODUCED A 40% INCREASE IN (2-14)C-ACETATE INCORPORATION INTO RUBRATOXIN. THE HIGHEST REDUCTION OF LABELED ACETATE INCORPORATION (36%) WAS CAUSED BY SUCCINATE OR ALPHA-KETOGLUTARATE COMBINED WITH MALONATE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

肝脏代谢丽红毒素。存在多种代谢物。在大鼠中，葡萄糖醛酸和硫酸结合物被排入胆汁，显然在小肠中被水解，并且母体毒素可能会通过肠肝循环再次被吸收。也会形成未知的代谢物。/丽红毒素/

THE LIVER METABOLIZES RUBRATOXINS. THERE ARE A NUMBER OF METABOLITES. IN RATS, GLUCURONIDE & SULFATE CONJUGATES ARE EXCRETED IN BILE, APPARENTLY HYDROLYZED IN THE INTESTINE, & THE PARENT TOXIN MAY BE RESORBED IN AN ENTEROHEPATIC CYCLE. UNKNOWN METABOLITES ARE ALSO FORMED. /RUBRATOXINS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

RUBRATOXINS 可能对增强同时受影响的饲料中产生的化合物的活性很重要，如黄曲霉毒素。

RUBRATOXINS MAY BE IMPORTANT IN POTENTIATING THE ACTIVITY OF COMPD SUCH AS AFLATOXINS SIMULTANEOUSLY PRODUCED IN AFFECTED FEEDS. /RUBRATOXINS/

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。如有必要，进行吸痰。观察呼吸不足的迹象，如有需要，协助通气。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……预计可能出现癫痫，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，用生理盐水连续冲洗每只眼睛……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，用干性无菌敷料覆盖皮肤烧伤……/毒药A和B/

/SRP:/ Basic treatment: Establish a patent airway. 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 normal saline 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 ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 解毒与急救

/SRP:/ 高级治疗：对于无意识、严重肺水肿或呼吸停止的患者，考虑进行口咽或鼻咽气管插管以控制气道。使用气囊面罩装置的正压通气技术可能有益。监测心率和必要时治疗心律失常... . 使用D5W开始静脉输液 /SRP: "保持开放"，最低流量/。如果出现低血容量的迹象，使用乳酸钠林格氏液。注意液体过载的迹象。考虑使用药物治疗肺水肿... . 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）治疗癫痫... . 使用丙美卡因氢氯化物协助眼部冲洗... . /毒药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 respiratory arrest. Positive pressure ventilation techniques with a bag valve mask device may be beneficial. Monitor cardiac rhythm and treat arrhythmias as necessary ... . Start an IV with D5W /SRP: "To keep open", minimal flow rate/. Use lactated Ringer's if signs of hypovolemia are present. Watch for signs of fluid overload. Consider drug therapy for pulmonary edema ... . For hypotension with signs of hypovolemia, administer fluid cautiously. Watch for signs of fluid overload ... . Treat seizures with diazepam (Valium) ... . Use proparacaine hydrochloride to assist eye irrigation ... . /Poison A and B/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/临床表现为厌食、脱水、抑郁、腹泻、黄疸和体重下降。猪可能表现出头部压迫、绞痛和腹部红斑。马可能会出现共济失调。死亡可能在短短12小时内发生。在鼠类中，会有胎儿死亡或发育迟缓或畸形的胎儿。总体印象是严重的出血性坏死性肝炎，伴有各种器官出血。脾脏也可能坏死。...在猫中，胆囊壁会水肿并有大量腹水。在马中，可能会有脑出血。/鲁布拉毒素/

/LABORATORY ANIMALS: Acute Exposure/ CLINICAL SIGNS INCL ANOREXIA, DEHYDRATION, DEPRESSION, DIARRHEA, JAUNDICE, & WT LOSS. SWINE MAY MANIFEST HEAD PRESSING, COLIC, & VENTRAL ERYTHEMA. HORSES MAY BECOME INCOORDINATED. DEATH OCCURS IN AS FEW AS 12 HR. IN MICE THERE ARE FETAL DEATHS OR STUNTED OR DEFORMED FETUSES. GENERAL IMPRESSION IS OF A SEVERE HEMORRHAGIC NECROTIZING HEPATITIS WITH HEMORRHAGES IN VARIOUS ORGANS. THE SPLEEN ALSO MAY BE NECROTIC. ... IN CATS THERE IS EDEMA OF THE WALL OF THE GALLBLADDER & MASSIVE ASCITES. IN HORSES THERE MAY BE BRAIN HEMORRHAGES. /RUBRATOXINS/

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 非人类毒性摘录

实验室动物：急性暴露/红斑毒素病目前并不是兽医毒理学中的一个独立实体，因为没有记录在案的单纯形式的病例。在其他霉菌毒素，尤其是黄曲霉毒素总是存在于发霉饲料中同时存在红斑毒素的案例中。/红斑毒素/

/LABORATORY ANIMALS: Acute Exposure/ RUBRATOXICOSIS IS NOT PRESENTLY A SEPARATE ENTITY IN VETERINARY TOXICOLOGY BECAUSE THERE ARE NO DOCUMENTED CASES OF AN UNCOMPLICATED FORM. OTHER MOLD TOXINS, PARTICULARLY AFLATOXINS, HAVE ALWAYS BEEN PRESENT IN CASES WHERE RUBRATOXINS WERE PRESENT IN MOLDY FEED. /RUBRATOXINS/

来源:Hazardous Substances Data Bank (HSDB)