Citrinin | 518-75-2

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: Citrinin
• 英文别名: (3R,4S)-6-hydroxy-3,4,5-trimethyl-8-oxo-3,4-dihydroisochromene-7-carboxylic acid
• CAS: 518-75-2；11118-72-2
• 化学式: C₁₃H₁₄O₅
• 分子量: 250.251
• InChiKey: CBGDIJWINPWWJW-IYSWYEEDSA-N

物化性质

• 颜色/状态：
  Lemon-yellow needles from alc
• 沸点：
  178-179 °C (decomposes)
• 溶解度：
  Practically insol in water; sol in alc, dioxane, dilute alkali
• 蒸汽压力：
  5.6X10-10 mm Hg at 25 °C /Estimated/
• 旋光度：
  Specific optical rotation: -37.4 deg at 18 °C/D (alc, 1.15%); max absorption: 250 nm, 331 nm (epsilon= 370, 418, 1%, 1 cm)
• 分解：
  Decomposed at 175 °C
• 碰撞截面：
  148 Ų [M+H]+ [CCS Type: TW, Method: calibrated with polyalanine]

计算性质

• 辛醇/水分配系数(LogP)：
  1.7
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

ADMET

代谢

在查尔斯河CD-1大鼠妊娠第12天进行皮下注射后，14C-桔霉素跨越了胎盘。... 对母体血浆提取物的母体血浆提取物进行高效液相色谱分析，揭示了母体化合物和至少一个未识别的代谢物的存在，该代谢物比母体化合物更具极性；在尿液中至少发现了两个未识别的代谢物。母体胆汁样本的色谱图表明，除了母体化合物外，还存在至少一个代谢物，而胎儿提取物中仅含有母体化合物。

Following subcutaneous injection on day 12 of gestation, 14C-citrinin crossed the placenta in Charles River CD-1 rats. ... High-performance liquid chromatography of maternal plasma extracts revealed the presence of the parent compound and at least one unidentified metabolite, which was more polar than the parent compound; at least two unidentified metabolites were found in urine. Chromatograms of maternal bile samples suggested the presence of at least one metabolite, apart from the parent compound, whereas fetal extracts contained only the parent compound.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性的证据有限。总体评估：第3组：该物质对人类致癌性无法分类。

No data are available in humans. Limited evidence of carcinogenicity in animals. OVERALL EVALUATION: Group 3: The agent is not classifiable as to its carcinogenicity to humans.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌物分类

国际癌症研究机构致癌物： citrinin

IARC Carcinogenic Agent:Citrinin

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构（IARC）致癌物分类：第3组：对人类致癌性尚无法分类

IARC Carcinogenic Classes:Group 3: Not classifiable as to its carcinogenicity to humans

来源:International Agency for Research on Cancer (IARC)

毒理性

• 致癌物分类

国际癌症研究机构专论：第40卷：（1986年）一些天然存在和合成的食品成分，呋喃香豆素和紫外线辐射

IARC Monographs:Volume 40: (1986) Some Naturally Occurring and Synthetic Food Components, Furocoumarins and Ultraviolet Radiation

来源:International Agency for Research on Cancer (IARC)

毒理性

• 相互作用

柑橘素抑制了在温度变化后4小时或2小时内施用在接种了烟草花叶病毒的N. glutinosa叶片上的局部病变诱导。

Citrinin inhibited local lesion induction on N. glutinosa leaves inoculated with tobacco mosaic virus. It was applied on leaves within 4 or 2 hr after the temp shift.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠肾皮质切片中... 14C-Citrinin的摄取被乳酸增强，并被丙磺舒（一种特异性阴离子转运抑制剂）所减少。二硝基苯酚是一种代谢抑制剂，也是阴离子转运的竞争性抑制剂，它也减少了Citrinin的转运。有机阳离子并未改变切片中Citrinin的积累。这些数据与Citrinin通过肾脏有机阴离子分泌系统的转运是一致的。

/In/ Rat renal cortical slices ... 14C-Citrinin uptake was enhanced by lactate and reduced by probenecid, a specific inhibitor of anion transport. Dinitrophenol is a metabolic inhibitor as well as competitive inhibitor of anion transport, and it also reduced citrinin transport. Organic cations did not alter citrinin accumulation by the slices. These data are consistent with the transport of citrinin by the renal organic anion secretory system.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

在大鼠静脉给药后0.5小时，观察到肝脏和肾脏中总放射性的百分比分别为14.7%和5.6%，到6小时时，肝脏降至7.5%，肾脏降至4.7%。血浆中(14)C的浓度从0.5小时的9.2%降至6小时的4.7%。血浆半衰期为2.6小时和14.9小时。大约80%在24小时内通过粪便和尿液排出。第二组大鼠在给药3毫克/千克(14)C-桔霉素之前4天，预先腹腔注射50毫克/千克桔霉素。尿液排出量增加。血浆消失曲线有两个消除速率，半衰期分别为0.6小时和14.1小时。肾毒性大鼠在示踪剂剂量后24小时内在肝脏保留7.5%的给药放射性，而恢复的大鼠为1.3%；72小时后，47%的(14)C通过粪便或结肠内容物排出，而恢复的大鼠为17.5%。在正常大鼠中，肾脏显然是主要的消除途径。

0.5 hr after iv administration of (14)C-labeled compound to rats, 14.7% & 5.6% of total radioactivity were observed in liver & kidneys respectively, & by 6 hr decreased to 7.5% in liver & 4.7% in kidney. Plasma concentration of (14)C decreased from 9.2% at 0.5 hr to 4.7% at 6 hr. Plasma /half-lives/ were 2.6 & 14.9 hr. Approx 80% was excreted in feces & urine by 24 hr. A 2nd group was pretreated with 50 mg/kg citrinin, ip, 4 days prior to administration of 3 mg/kg (14)C-citrinin, iv. Urine output was enhanced. Plasma disappearance curve had 2 elimination rates, with /half-lives/ of 0.6 & 14.1 hr. Nephrotoxic rats retained 7.5% of the administered radioactivity in liver compared to 1.3% in recovered rats 24 hr after tracer dose & 47% of (14)C was excreted in feces or in colon contents after 72 hr compared to 17.5% in recovered rats. In normal rats the kidneys apparently are major route of elimination.

来源:Hazardous Substances Data Bank (HSDB)

吸收、分配和排泄

柑橘素（25-50 mg/kg）据报道在大鼠的胃肠道和猫的口腔吸收不良。

Citrinin (25-50 mg/kg) has been reported to be poorly absorbed from the gastrointestinal tract of rats and from the mouth of cats.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险品标志：
  T
• 安全说明：
  S26,S36/37/39,S45
• 危险类别码：
  R23/24/25,R40,R36/37/38
• WGK Germany：
  3
• 海关编码：
  29419090
• 危险品运输编号：
  UN 3462 6.1/PG 3
• RTECS号：
  DJ2275000
• 包装等级：
  II
• 危险类别：
  6.1(a)

制备方法与用途

类别：有毒物品
毒性分级：剧毒
急性毒性：口服-大鼠 LD50: 28 毫克/公斤；口服-小鼠 LD50: 1.7 毫克/公斤
可燃性危险特性：可燃，燃烧时产生刺激烟雾
储运特性：库房通风、低温干燥，并与食品原料分开存放
灭火剂：干粉、泡沫、沙土、二氧化碳或雾状水

反应信息

• 作为反应物：
  描述：

  Citrinin 生成 桔霉素
  参考文献：
  名称：

  Carbon-13 NMR of Citrinin in the Solid State and in Solutions

  摘要：

  Carbon-13 NMR is used to study the tautomeric equilibrium of citrinin in the solid state. The results confirm earlier X-ray diffraction studies, which indicated that the compound crystallizes in a disordered structure, with the p-quinone and o-quinone forms in a dynamic equilibrium. Analysis of the NMR data yields the equilibrium constant K(T) = [o]/[p] = exp(4.2/R) exp(-1610/RT) (where R is in cal mol(-1) K-1), which is essentially identical to that determined by X-ray. The tautomerism is extremely fast on the NMR time scale (>10(6) s(-1)). In methylene chloride solution citrinin also exists as a fast interconverting mixture of the two isomers with an equilibrium constant K similar to 0.7 at room temperature. However, the temperature dependence of the carbon-13 and oxygen-17 chemical shifts gave conflicting results, thus preventing a reliable determination of the thermodynamic parameters of K. In methanol and methanol/methylene chloride mixtures, citrinin undergoes a nucleophilic, Michael type, addition. The reaction is reversible, and the equilibrium shifts toward the normal citrinin form upon increasing temperature and in methanol/methylene chloride mixtures with increasing methylene chloride fraction. Only normal citrinin is obtained on crystallization, even from neat methanol.

  DOI：

  10.1021/jp970681t
• 作为产物：
  描述：

  桔霉素 生成 Citrinin
  参考文献：
  名称：

  Carbon-13 NMR of Citrinin in the Solid State and in Solutions

  摘要：

  Carbon-13 NMR is used to study the tautomeric equilibrium of citrinin in the solid state. The results confirm earlier X-ray diffraction studies, which indicated that the compound crystallizes in a disordered structure, with the p-quinone and o-quinone forms in a dynamic equilibrium. Analysis of the NMR data yields the equilibrium constant K(T) = [o]/[p] = exp(4.2/R) exp(-1610/RT) (where R is in cal mol(-1) K-1), which is essentially identical to that determined by X-ray. The tautomerism is extremely fast on the NMR time scale (>10(6) s(-1)). In methylene chloride solution citrinin also exists as a fast interconverting mixture of the two isomers with an equilibrium constant K similar to 0.7 at room temperature. However, the temperature dependence of the carbon-13 and oxygen-17 chemical shifts gave conflicting results, thus preventing a reliable determination of the thermodynamic parameters of K. In methanol and methanol/methylene chloride mixtures, citrinin undergoes a nucleophilic, Michael type, addition. The reaction is reversible, and the equilibrium shifts toward the normal citrinin form upon increasing temperature and in methanol/methylene chloride mixtures with increasing methylene chloride fraction. Only normal citrinin is obtained on crystallization, even from neat methanol.

  DOI：

  10.1021/jp970681t

文献信息

• Carbon-13 NMR of Citrinin in the Solid State and in Solutions
  作者：R. Poupko、Z. Luz、R. Destro

  DOI：10.1021/jp970681t

  日期：1997.7.1

  Carbon-13 NMR is used to study the tautomeric equilibrium of citrinin in the solid state. The results confirm earlier X-ray diffraction studies, which indicated that the compound crystallizes in a disordered structure, with the p-quinone and o-quinone forms in a dynamic equilibrium. Analysis of the NMR data yields the equilibrium constant K(T) = [o]/[p] = exp(4.2/R) exp(-1610/RT) (where R is in cal mol(-1) K-1), which is essentially identical to that determined by X-ray. The tautomerism is extremely fast on the NMR time scale (>10(6) s(-1)). In methylene chloride solution citrinin also exists as a fast interconverting mixture of the two isomers with an equilibrium constant K similar to 0.7 at room temperature. However, the temperature dependence of the carbon-13 and oxygen-17 chemical shifts gave conflicting results, thus preventing a reliable determination of the thermodynamic parameters of K. In methanol and methanol/methylene chloride mixtures, citrinin undergoes a nucleophilic, Michael type, addition. The reaction is reversible, and the equilibrium shifts toward the normal citrinin form upon increasing temperature and in methanol/methylene chloride mixtures with increasing methylene chloride fraction. Only normal citrinin is obtained on crystallization, even from neat methanol.