[(7S,8R)-7-[(Z)-2-methylbut-2-enoyl]oxy-5,6,7,8-tetrahydro-3H-pyrrolizin-1-yl]methyl (2R)-2,3-dihydroxy-2-(1-methoxyethyl)-3-methylbutanoate | 303-34-4

• 分子结构分类: 有机化合物 - 生物碱及其衍生物
• 英文名称: [(7S,8R)-7-[(Z)-2-methylbut-2-enoyl]oxy-5,6,7,8-tetrahydro-3H-pyrrolizin-1-yl]methyl (2R)-2,3-dihydroxy-2-(1-methoxyethyl)-3-methylbutanoate
• CAS: 303-34-4
• 化学式: C₂₁H₃₃NO₇
• 分子量: 411.5
• InChiKey: QHOZSLCIKHUPSU-SVQULCFASA-N

物化性质

• 熔点：
  96.5-97.0℃
• 比旋光度：
  D -4° (10% alc)
• 沸点：
  531.2°C (rough estimate)
• 密度：
  1.21±0.1 g/cm3 (20 ºC 760 Torr)
• LogP：
  1.280
• 物理描述：
  Lasiocarpine appears as colorless plates or beige crystalline solid. (NTP, 1992)
• 颜色/状态：
  COLORLESS PLATES
• 溶解度：
  less than 0.1 mg/mL at 68° F (NTP, 1992)
• 稳定性/保质期：
  DECOMP SLOWLY ON STANDING IN AIR @ ROOM TEMP
• 旋光度：
  SPECIFIC OPTICAL ROTATION: -3.0 DEG @ 16 °C/D (IN ETHANOL)
• 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)：
  0.5
• 重原子数：
  29
• 可旋转键数：
  10
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.71
• 拓扑面积：
  106
• 氢给体数：
  2
• 氢受体数：
  8

ADMET

代谢

使用毛果芸香碱的研究已经确认了由大鼠肝微粒体混合功能氧化酶系统形成的吡咯代谢物。去氢毛果芸香碱已被分离并鉴定为毛果芸香碱微粒体氧化的产物。

STUDIES WITH LASIOCARPINE HAVE CONFIRMED THE FORMATION OF PYRROLIC METABOLITES BY THE MIXED-FUNCTION OXIDASE SYSTEM OF THE MICROSOMAL FRACTION OF RAT LIVER. DEHYDROHELIOTRIDINE HAS BEEN ISOLATED & IDENTIFIED AS A PRODUCT OF MICROSOMAL OXIDATION OF LASIOCARPINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

在尿液中...在大鼠注射后16小时获得...未改变的毛果芸香碱（剂量的1-1.5%），日照飞蓬碱（1.5-3%），日照飞蓬碱N-氧化物（6%）和带有欧普因和7-天使日照飞蓬碱（预期部分水解产物）色谱性质的少量碱基。...24小时尿液样本中的代谢物...给药毛果芸香碱的8.5%。

IN URINE ... OBTAINED 16 HR AFTER INJECTION ... TO RATS ... UNCHANGED LASIOCARPINE (1-1.5% OF DOSE), HELIOTRIDINE (1.5-3%), HELIOTRIDINE N-OXIDE (6%) & TRACES OF BASES WITH CHROMATOGRAPHIC PROPERTIES OF EUROPINE & 7-ANGELYHELIOTRIDINE (EXPECTED PRODUCTS OF PARTIAL HYDROLYSIS). ... METABOLITES IN 24-HR URINE SAMPLE ... 8.5% OF ADMIN LASIOCARPINE.

来源:Hazardous Substances Data Bank (HSDB)

代谢

人类胚胎肝脏切片将吡咯里西啶生物碱LASIOCARPINE转化为吡咯，这通过正艾尔利希显色反应得到指示，而肺组织则没有。

HUMAN EMBRYONIC LIVER SLICES CONVERTED THE PYRROLIZIDINE ALKALOID LASIOCARPINE INTO PYRROLES, AS INDICATED BY A POS EHRLICH COLOR REACTION, WHEREAS LUNG TISSUE DID NOT.

来源:Hazardous Substances Data Bank (HSDB)

毒理性

• 致癌性证据

致癌性分类：1）人类证据：不可用；2）动物证据：充分。对人类致癌风险的总体评估为2B组：该物质可能对人类致癌。/来自表格/

Classification of carcinogenicity: 1) evidence in humans: not available; 2) evidence in animals: sufficient. Overall summary evaluation of carcinogenic risk to humans is Group 2B: The agent is possibly carcinogenic to humans. /From table/

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：鹰靛蓝

IARC Carcinogenic Agent:Lasiocarpine

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：2B组：可能对人类致癌

IARC Carcinogenic Classes:Group 2B: Possibly carcinogenic 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病例。

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

LASROCARPINE（随机标记，44%在氨基醇中）通过静脉给药给大鼠（总剂量为5毫克），4小时后标记分布如下：胴体，6.4%；肠道，8.6%；睾丸，0.1%；肺，0.05%；肾脏，0.26%；心脏，0.05%；脾，0.01%；大脑，0.03%；尿液，27.2%；肝脏，2.8%，呼出的二氧化碳，9.3% 肝部分馏得到1.73%在三氯乙酸提取物中，蛋白质中0.6%，脂质中0.48%，核酸中0.005%。

LASROCARPINE (RANDOMLY LABELLED, 44% IN THE AMINO ALCOHOL) WAS ADMIN IP TO RATS (TOTAL DOSE, 5 MG) DISTRIBUTION OF LABEL AFTER 4 HR WAS AS FOLLOWS: CARCASS, 6.4%; INTESTINES, 8.6%; TESTES, 0.1%; LUNG, 0.05%; KIDNEY, 0.26%; HEART, 0.05%; SPLEEN, 0.01%; BRAIN, 0.03%; URINE, 27.2%; LIVER, 2.8%, EXPIRED CO2, 9.3% FRACTIONATION OF LIVER RESULTED IN 1.73% IN A TRICHLOROACETIC ACID EXTRACT, 0.6% IN PROTEIN, 0.48% IN LIPID & 0.005% IN NUCLEIC ACIDS.

来源:Hazardous Substances Data Bank (HSDB)

安全信息

• 危险等级：
  6.1(b)
• 危险类别：
  6.1(b)
• 包装等级：
  III