(4S)-7-hydroxy-3',6,7-trimethylspiro[2,9-dioxa-14-azatricyclo[9.5.1.014,17]heptadec-11-ene-4,2'-oxirane]-3,8-dione | 6870-67-3

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: (4S)-7-hydroxy-3',6,7-trimethylspiro[2,9-dioxa-14-azatricyclo[9.5.1.014,17]heptadec-11-ene-4,2'-oxirane]-3,8-dione
• CAS: 6870-67-3；471-14-7
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: IAPHXJRHXBQDQJ-LOHAKXRJSA-N

物化性质

• 熔点：
  228°C
• 沸点：
  485.2°C (rough estimate)
• 密度：
  1.2737 (rough estimate)
• 颜色/状态：
  Colorless plates
• 溶解度：
  In water, 1.5X10+5 mg/L @ 25 °C /Estimated/
• 蒸汽压力：
  9.3X10-13 mm Hg @ 25 °C /Estimated/
• 稳定性/保质期：
  Stable at room temp in closed containers; slightly volatile
• 旋光度：
  Specific optical rotation (chloroform): -40 deg at 20 °C/D
• 分解：
  When heated to decomposition it emits toxic fumes of /nitrogen oxides/.

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  25
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.78
• 拓扑面积：
  88.6
• 氢给体数：
  1
• 氢受体数：
  7

ADMET

代谢

通常，肝脏毒性吡咯烷生物碱在大鼠肝脏中被代谢，产生水解产物、N-氧化物和脱氢吡咯里西啶（吡咯衍生物）。根据目前的证据，后一组物质似乎介导了生物碱的大多数毒性反应。这些吡咯衍生物是由肝细胞的混合功能氧化酶产生的。从生物碱（例如雅各宾碱...）的 retronecine 酯形成的初始产物很可能是脱氢生物碱。脱氢生物碱是高度反应性的烷基化剂，它们会立即与细胞成分反应，产生可溶的或结合的次级代谢物，或者水解生成脱氢氨基醇。/吡咯里西啶生物碱/

In general, the hepatotoxic pyrrolidine alkaloids are metabolized in rat liver to give hydrolysis products, n-oxides and dehydropyrrolizidine (pyrrolic) deriv. The latter group appears on current evidence to mediate most of toxic reactions of alkaloids. These pyrrolic deriv are produced by mixed-function oxidases of liver cells. Initial product formed from alkaloids that are esters of...retronecine (eg, jacobine...) is very probably the dehydroalkaloid. Dehydroalkaloids are highly reactive alkylating agents which react immediately with cell constituents to give soluble or bound secondary metabolites or which hydrolyze to dehydroaminoalcohol. /pyrrolizidine alkaloids/

来源:Hazardous Substances Data Bank (HSDB)

代谢

长时间使用苯巴比妥（pb）对千里光（sj）毒性的影响在绵羊身上进行了研究。结果表明，pb诱导的混合功能氧化酶并未增加绵羊对sj中毒的易感性。绵羊具有高活性的肝微粒体环氧化物水解酶，这可能是它们对sj中毒产生抵抗力的原因。

The effect of prolonged phenobarbital (pb) administration on the toxicity of Senecio jacobaea (sj) was studied in sheep. Results suggested that mixed-function oxidase induction by pb does not increase the susceptibility of sheep to sj intoxication. Sheep possess a high activity of hepatic microsomal epoxide hydrolase which could account for their resistance to sj intoxication.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在伪一级反应条件下，对一系列半合成吡咯酯和吡咯啉生物碱的烷基化活性进行了比较。雅各宾吡咯（雅各宾的一种活性代谢物）的烷基化数据符合简单的一级速率表达式。雅各宾吡咯反应速率的大幅增加提示了靠近C-7酯基的环氧环可能产生的电子场效应。

Comparison is made of the alkylating activities of a series of semi-synthetic pyrrole esters and pyrrole derivatives of pyrrolizidine alkaloids under pseudo-first-order reaction conditions. Data for alkylation by jacobine pyrrole (a reactive metabolite of jacobine) fit a simple first-order rate expression for product formation. The large increase in reaction rate for jacobine pyrrole is suggestive of an electronic field effect due to the epoxide ring in proximity to the C-7 ester moiety.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

没有关于人类的数据。动物致癌性证据不足。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. Inadequate 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剂：Jacobine

IARC Carcinogenic Agent:Jacobine

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：无法归类其对人类致癌性

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著：第10卷：（1976年）一些天然存在的物质

IARC Monographs:Volume 10: (1976) Some Naturally Occurring Substances

来源:International Agency for Research on Cancer (IARC)

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

吸收、分配和排泄

饮食中添加铜和锌对兔子的吡咯烷生物碱（PAs）的排泄没有影响。从千里光中分离出的PAs在体外实验中能够轻易地穿过隔离的空肠和回肠的粘膜，逆着浓度梯度转移。这些结果表明，饮食中千里光对矿物质代谢改变的影响并不是由于胃肠道矿物质吸收的变化。此外，兔子对饮食中千里光中毒的抗性似乎并不是由于吡咯烷生物碱在胃肠道吸收低，而是由于高效的尿液排出。

Excretion of pyrrolizidine alkaloids (pa's) in diet of rabbits was not affected by the addition of copper and zinc to the diet. Isolated pa's from Senecio jacobaea were found to be readily transferred across the mucosa of isolated everted sacs of jejunum and ileum in vitro against a concentration gradient. These results suggest that the effects of dietary Senecio jacobaea on alterations in mineral metabolism are not due to changes in GI mineral absorption. In addition, it appears that the resistance of rabbits to dietary Senecio jacobaea intoxication is not caused by low GI absorption of pyrrolizidine alkaloids, but rather by efficient urinary elimination.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 包装等级：
  III
• 危险类别：
  6.1(b)
• 危险品运输编号：
  UN 1544