jacobine | 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: jacobine
• 英文别名: Jacobin；(15alpha,20R)15,20-Epoxy-15,20-dihydro-12-hydroxy-senecionan-11,16-dione；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
• 化学式: C₁₈H₂₅NO₆
• 分子量: 351.4
• InChiKey: IAPHXJRHXBQDQJ-UHFFFAOYSA-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）排泄没有影响。从千里光属植物Jacobaea分离出的PAs在体外实验中能够轻易地穿越空肠和回肠的隔离翻转型囊袋的粘膜，对抗浓度梯度。这些结果表明，饮食中千里光属植物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属植物的毒性抵抗似乎并不是由于吡咯烷生物碱的胃肠道吸收低，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

文献信息

• [EN] TWO-CARBON LINKED ARTEMISININ-DERIVED TRIOXANE DIMERS<br/>[FR] DIMÈRES DE TRIOXANE DÉRIVÉS D'ARTÉMISININE LIÉS À DEUX ATOMES DE CARBONE
  申请人：UNIV JOHNS HOPKINS

  公开号：WO2014116642A1

  公开（公告）日：2014-07-31

  Two-carbon linked artemisinin-derived trioxane dimers and methods of their use for treating subjects infected with malaria or other parasitic infectious diseases including, but not limited to, toxoplasmic infection; subjects afflicted with psychiatric conditions associated with toxoplasmic infection; and subjects afflicted with cancer.

  两碳键合的青蒿素衍生三氧杂环二聚体及其用于治疗感染疟疾或其他寄生虫传染病的方法，包括但不限于弓形虫感染；患有与弓形虫感染相关的精神疾病的受试者；以及患有癌症的受试者。
• Hole-transporting polymers
  申请人：——

  公开号：US20010017155A1

  公开（公告）日：2001-08-30

  Polymers comprising triarylamine substituent monomers. The polymers are products of anionic or radical polymerization of monovinylated triarylamine monomers or of ROMP polymerization of monomers comprising a triarylamine component, a linker component, and a cyclic olefin that is capable of undergoing a ring-opening polymerization reaction. The resulting polymers possess hole-transporting properties and are useful as hole transport layers in light-emitting diodes or as components of photorefractive materials.

  包含三芳胺取代单体的聚合物。这些聚合物是单乙烯化三芳胺单体的阴离子或自由基聚合或由包含三芳胺组分、连接组分和能够进行环开启聚合反应的环烯烃的ROMP聚合单体聚合而成。所得到的聚合物具有传输空穴的性质，可用作发光二极管中的空穴传输层或作为光折变材料的组分。
• Monomers and polymers for optical elements
  申请人：Jethmalani Jagdish

  公开号：US20060052547A1

  公开（公告）日：2006-03-09

  Compositions comprising a matrix polymer and a mixture of monomers are used for making polymer mixtures containing the matrix polymer and a second polymer formed from the monomer mixture. Preferably, the matrix polymer comprises a polyester, polystyrene, polyacrylate, thiol-cured epoxy polymer, thiol-cured isocyanate polymer, or mixtures thereof. Preferably, the monomer mixture comprises a thiol monomer and at least one second monomer selected from the group consisting of ene monomer and yne monomer. The compositions may be used to fabricate optical elements such as lenses.

  该组合物包括一个基质聚合物和一种单体混合物，用于制造含有基质聚合物和由单体混合物形成的第二聚合物的聚合物混合物。首选，基质聚合物包括聚酯，聚苯乙烯，聚丙烯酸酯，硫醇固化环氧聚合物，硫醇固化异氰酸酯聚合物或其混合物。首选，单体混合物包括硫醇单体和至少一种从烯烃单体和炔烃单体组成的第二单体。该组合物可用于制造光学元件，如透镜。
• Polymerisable compositions and organic light-emitting devices containing them
  申请人：Steudel David Annette

  公开号：US20060057423A1

  公开（公告）日：2006-03-16

  Compositions of a mixture of a thiol material and a material that contains a reactive unsaturated carbon-carbon bond that can be polymerised to form a charge-transporting or luminescent film are described, as is an organic light-emitting diode (OLED) device comprising at least one such charge-transporting or emissive layer that has been formed by polymerising a thiol material and an ene material. The process for forming such an OLED, including the deposition of a layer of material comprising the polymerisable composition, from solution, exposing said layer to actinic radiation through a mask, and then optionally developing said film to form a photopatterned film, is also disclosed.

  本文描述了一种由硫醇材料和含有可聚合以形成带电荷或发光薄膜的反应性不饱和碳碳键材料混合而成的组合物，以及至少包含一种这样的带电荷或发射层的有机发光二极管（OLED）器件，该层是通过聚合硫醇材料和烯烃材料形成的。还公开了制备这种OLED的过程，包括从溶液中沉积包含可聚合组分的材料层，通过掩膜暴露该层至光敏辐射，然后可选地开发该膜以形成光图案膜。
• Electroluminescent device
  申请人：Steudel Annette

  公开号：US20060216411A1

  公开（公告）日：2006-09-28

  A method of forming an electroluminescent device comprising the steps of: providing a substrate comprising a first electrode for injecting charge carriers of a first type; forming an electroluminescent layer having a surface by depositing onto the substrate a composition comprising a host material and a light-emitting dopant monomer of formula (I): A-C—(X) n (I) wherein X represents a polymerisable group; A represents a light-emitting group; C represents a bond or a spacer group and n is an integer; rendering at least some of the electroluminescent layer insoluble in a solvent by polymerising the monomer of formula (I); exposing the electroluminescent layer to the solvent; and depositing a second electrode capable of injecting charge carriers of a second type over the electroluminescent layer.

  一种形成电致发光器件的方法，包括以下步骤：提供一个基底，该基底包括用于注入第一类型载流子的第一电极；通过在基底上沉积包括主体材料和式(I)的发光掺杂单体的组合物来形成具有表面的电致发光层：A-C-(X)n(I)，其中X代表可聚合基团，A代表发光基团，C代表键或间隔基团，n为整数；通过聚合式(I)的单体使至少部分电致发光层在溶剂中不溶；将电致发光层暴露于溶剂中；并在电致发光层上沉积能够注入第二类型载流子的第二电极。