(2S,3S)-2-hydroxy-3-[(1S)-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-5,7,13,15-tetrone | 21794-01-4

• 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,3S)-2-hydroxy-3-[(1S)-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-5,7,13,15-tetrone
• CAS: 21794-01-4
• 化学式: C₂₆H₃₀O₁₁
• 分子量: 518.5
• InChiKey: ZJTBTDVZNGBSNG-WURQEVEGSA-N

物化性质

• 熔点：
  176°C
• 沸点：
  522.6°C (rough estimate)
• 密度：
  1.2767 (rough estimate)
• 颜色/状态：
  CRYSTALIZES FROM DIETHYL ETHER AS ROSETTES OF NEEDLES; FROM BENZENE & ETHYL ACETATE AS LONG LATHES; HEXAGONAL PLATES FROM AMYL ACETATE
• 稳定性/保质期：

  STABLE AT ROOM TEMP /RUBRATOXINS/

• 旋光度：
  Specific optical rotation: +67 deg (acetone, 20 °C, c=2)
• 分解：
  When heated to decomposition it emits acrid smoke and irritating fumes.
• 解离常数：
  PKA= 4.69

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  37
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.58
• 拓扑面积：
  174
• 氢给体数：
  3
• 氢受体数：
  11

ADMET

代谢

三羧酸循环不仅用于将葡萄糖完全氧化成二氧化碳和水，还为一些次级代谢物的生物合成提供中间体，包括类胡萝卜素毒素...第一步涉及癸酸与草酰乙酸的缩合，这一过程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，该酐二聚化并在进一步氧化后形成类胡萝卜素毒素A。氧气功能在哪个阶段引入尚不清楚，特别是，这样一个假设将意味着α,β-不饱和γ-内酯的羧基来自乙酸盐的甲基碳。/类胡萝卜素毒素/

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. /RUBRATOXINS/

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

• 副作用

职业性肝毒素 - 第二性肝毒素：在职业环境中的毒性效应潜力是基于人类摄入或动物实验的中毒案例。

Occupational hepatotoxin - Secondary hepatotoxins: the potential for toxic effect in the occupational setting is based on cases of poisoning by human ingestion or animal experimentation.

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

毒理性

• 相互作用

在接受了红毒素B（25毫克/千克，每周三次，持续5周）处理并在此期间喂食含有0.1 ppm的黄曲霉毒素B1饮食的大鼠中，发现了红毒素B致死作用增强的证据，但并未发现黄曲霉毒素B1致癌作用的增强。

EVIDENCE OF POTENTIATION OF THE LETHAL ACTION OF RUBRATOXIN B, BUT NOT THE CARCINOGENIC ACTION OF AFLATOXIN B1, WAS FOUND IN RATS TREATED WITH RUBRATOXIN B (25 MG/KG, 3 TIMES/WK FOR 5 WK) & FED OVER THE SAME PERIOD A DIET CONTAINING 0.1 PPM AFLATOXIN B1.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

在同时给药实验中，使用 Sprague-Dawley 大鼠，当存在 5 毫克/公斤的rubratoxin B时，ochratoxin A的新生儿LD50值比单独ochratoxin A的LD50值降低了16倍。在ochratoxin存在的情况下，rubratoxin B的新生儿LD50降低了4倍。在实验中，当第一天给予rubratoxin B，第十五天给予aflatoxin B1时，体重的减少是由两种物质共同作用而不是单独作用引起的。然而，当第一天给予aflatoxin B1或者在使用ochratoxin后接着使用rubratoxin的实验中，并没有显示出协同反应。

IN SIMULTANEOUS DOSING EXPT /WITH SPRAGUE-DAWLEY RATS/, THE NEONATE LD50 VALUE OF OCHRATOXIN A IN THE PRESENCE OF 5 MG/KG RUBRATOXIN B WAS REDUCED 16-FOLD BELOW THE LD50 VALUE OF OCHRATOXIN A ALONE. THE NEONATE LD50 OF RUBRATOXIN B WAS DECR 4-FOLD IN THE PRESENCE OF OCHRATOXIN. IN EXPT WHEN RUBRATOXIN B WAS ADMIN ON DAY ONE & AFLATOXIN B1 ON DAY 15, DECR WT GAINS WERE MEDIATED BY BOTH AGENTS RATHER THAN BY EITHER AGENT ALONE. A SYNERGISTIC RESPONSE, HOWEVER, WAS NOT DEMONSTRATED WHEN AFLATOXIN B1 WAS GIVEN ON DAY 1 OR IN EXPT USING OCHRATOXIN FOLLOWED BY RUBRATOXIN.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

使用丙二醇作为溶剂，雄性小鼠的急性腹腔LD50估计为1.42毫克/千克。戊巴比妥预处理可降低毒性约42%，而阉割或预先使用SKF-525A分别增加毒性20%和60%。红霉素B增强了戊巴比妥诱导的CNS抑制和增强戊巴比妥低体温。在另一实验中...戊巴比妥预处理可降低毒性约20%，而SKF-525A预处理可增加毒性近50%。二乙基马来酸盐预处理也显示出增强的毒性，这表明谷胱甘肽具有保护作用。这些数据表明，增加混合功能氧化酶活性与降低红霉素B毒性有关，进一步暗示红霉素B而非代谢物是活性形式。

USING PROPYLENE GLYCOL AS THE SOLVENT, THE ACUTE IP LD50 IN MALE MICE WAS EST AT 1.42 MG/KG. PRETREATMENT WITH SC PELLETS OF PENTOBARBITAL REDUCED TOXICITY APPROX 42% WHILE CASTRATION OR PRETREATMENT WITH SKF-525A INCR TOXICITY 20% & 60%, RESPECTIVELY. RUBRATOXIN B POTENTIATED PENTOBARBITAL-INDUCED /SRP: CNS DEPRESSION/ & ENHANCED PENTOBARBITAL HYPOTHERMIA. /IN ANOTHER EXPT/...PRETREATMENT WITH PENTOBARBITAL REDUCED TOXICITY APPROX 20% WHILE SKF-525A PRETREATMENT INCR TOXICITY NEARLY 50%. DIETHYL MALEATE PRETREATMENT ALSO DEMONSTRATED ENHANCED TOXICITY, SUGGESTING A PROTECTIVE ACTION OF GLUTATHIONE. THESE DATA SUGGEST THAT INCR MIXED FUNCTION OXIDASE ACTIVITY IS ASSOC WITH DECR RUBRATOXIN B TOXICITY, FURTHER IMPLYING THAT RUBRATOXIN B & NOT A METABOLITE IS THE ACTIVE FORM.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 相互作用

单独使用鲁布腊毒素以及与黄曲霉毒素联合口服给予豚鼠3周...产生的死亡率高于单独使用鲁布腊毒素所产生的。

THE EFFECTS OF RUBRATOXIN ALONE IN COMBINATION WITH AFLATOXIN GIVEN ORALLY TO GUINEA PIGS...FOR 3 WK PRODUCED MORTALITY HIGHER THAN PRODUCED BY RUBRATOXIN ALONE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

放射性标记的rubratoxin B（14）C在小鼠和大鼠中的排泄模式...在最初的24小时内排出了40-50%的放射性剂量。主要的排泄途径是通过呼吸的CO2，在小鼠中占给药（14）C的30%，在大鼠中占35%。6到9%通过尿液排出；粪便中存在的放射性活性较少。来自rubratoxin的放射性活性在给药后一小时内以最大水平出现在肝脏和肾脏中；其他器官中发现了较小的量。放射性活性的浓度在肝脏组织中最高。

EXCRETION PATTERNS OF (14)C DERIVED FROM RADIOLABELED RUBRATOXIN B...IN MICE & RATS...EXCRETED 40-50% OF THE ADMIN RADIOACTIVITY DURING THE INITIAL 24 HR. A MAJOR EXCRETORY ROUTE WAS RESP CO2 WHICH ACCOUNTED FOR 30% OF THE ADMIN (14)C IN MICE & 35% IN RATS. 6 TO 9% WAS EXCRETED IN THE URINE; LESS RADIOACTIVITY WAS PRESENT IN FECES. RADIOACTIVITY DERIVED FROM RUBRATOXIN WAS PRESENT AT MAX LEVELS IN LIVER & KIDNEYS ONE HR AFTER ADMIN; SMALLER AMT WERE FOUND IN OTHER ORGANS. THE CONCN OF RADIOACTIVITY WAS GREATEST IN LIVER TISSUE.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

源自放射性标记的RUBRATOXIN B（14）C的排泄模式...在小鼠和大鼠中。 ...在注射后1/2小时内，所有可检测到的放射性都存在于微粒体上清液中。在前2小时内，线粒体中的放射性物质逐渐增加，而微粒体上清液中的放射性物质相应减少。在24小时时，线粒体部分含有大约14%的肝脏放射性，而80%的放射性仍留在溶液部分。在24小时期间，微粒体部分含有4%到10%的肝脏放射性。

EXCRETION PATTERNS OF (14)C DERIVED FROM RADIOLABELED RUBRATOXIN B...IN MICE & RATS. ...ALL DETECTABLE RADIOACTIVITY PRESENT IN THE LIVER 1/2 HR AFTER INJECTION WAS IN THE MICROSOMAL SUPERNATANT FLUID. WITHIN THE FIRST 2 HR, INCR AMT OF RADIOACTIVITY WERE FOUND IN THE MITOCHONDRIA WITH A CONCOMITANT DECR IN THE MICROSOMAL SUPERNATANT FLUID. AT 24 HR, THE MITOCHONDRIAL FRACTION CONTAINED APPROX 14% OF THE LIVER RADIOACTIVITY WITH 80% REMAINING IN THE SOL FRACTION. THE MICROSOMAL FRACTION CONTAINED 4 TO 10% OF THE LIVER RADIOACTIVITY DURING THE 24-HR PERIOD.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

排泄、肾脏和肝脏组织浓度以及从血浆浓度估算的药代动力学参数对单次静脉注射(14)C-红毒素B的大鼠进行了测定（0.05毫克溶于丙二醇中）。到第7天，80%的管理放射性已排泄入尿液（41.7%）和粪便（38.7%）。尿排泄主要是以原型化合物为主，占7天内排泄放射性物质的75%。肾脏中放射性物质的消除是单相的，半衰期为97.35小时。肝脏中放射性物质的消除是双相的，慢相的半衰期为13.66小时。红毒素B及其衍生的放射性物质（来自原型化合物和代谢物）从血浆中的消除也是双相的。消除的快速相半衰期为2.57和1.08小时，慢相半衰期为60.80和100.46小时，分别对应红毒素B和(14)C-红毒素B衍生的放射性物质。长的血浆半衰期提示存在肠肝循环。放射性物质浓度在肝脏中最高的是在1小时，在血浆中最高的是在2小时。除了注射后最初的几小时外，肝脏中的放射性物质浓度从未显著超过血浆中的浓度，这表明存在被动吸收过程。

EXCRETION, TISSUE CONCN IN KIDNEY & LIVER, & PHARMACOKINETIC PARAMETERS ESTIMATED FROM PLASMA BLOOD CONCN WERE DETERMINED FOR RATS GIVEN A SINGLE IP DOSE OF (14)C-RUBRATOXIN B (0.05 MG DISSOLVED IN PROPYLENE GLYCOL). BY 7 DAYS, 80% OF ADMIN RADIOACTIVITY WAS EXCRETED INTO THE URINE (41.7%) & FECES (38.7%). URINARY EXCRETION WAS PRIMARILY AS THE PARENT COMPOUND, ACCOUNTING FOR 75% OF RADIOACTIVITY EXCRETED BY 7 DAYS. ELIMINATION OF RADIOACTIVITY FROM KIDNEYS WAS MONOPHASIC WITH T/2 OF 97.35 HR. ELIMINATION OF RADIOACTIVITY FROM LIVER WAS BIPHASIC, WITH T/2 OF 13.66 HR FOR THE SLOW PHASE. ELIMINATION OF RUBRATOXIN B & (14)C-RUBRATOXIN B-DERIVED RADIOACTIVITY (RADIOACTIVITY DERIVED FROM BOTH THE PARENT COMPOUND & METABOLITES) FROM PLASMA WAS BIPHASIC. THE RAPID PHASES OF ELIMINATION HAD T/2 OF 2.57 & 1.08 HR, & SLOW PHASES HAD T/2 OF 60.80 & 100.46 HR FOR RUBRATOXIN B & (14)C-RUBRATOXIN B-DERIVED RADIOACTIVITY RESPECTIVELY. THE LONG PLASMA T/2 IS SUGGESTIVE OF ENTEROHEPATIC CIRCULATION. THE CONCN OF RADIOACTIVITY WAS GREATEST AT 1 HR IN LIVER & 2 HR IN PLASMA. EXCEPT FOR THE FIRST FEW HR FOLLOWING INJECTION, THE CONCN OF RADIOACTIVITY IN LIVER NEVER EXCEEDED SIGNIFICANTLY THAT IN THE PLASMA, SUGGESTING A PASSIVE ABSORPTION PROCESS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险品标志：
  Xn
• 危险类别码：
  R22
• RTECS号：
  GX9275000
• 包装等级：
  III
• 危险类别：
  6.1(b)