去氢倒千里光裂碱 | 26400-45-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯嗪
• 中文名称: 去氢倒千里光裂碱
• 英文名称: (+/-)-6,7-dihydro-7-hydroxy-1-(hydroxymethyl)-5H-pyrrolizine
• 英文别名: DHP；1H-Pyrrolizine-7-methanol, 2,3-dihydro-1-hydroxy-；7-(hydroxymethyl)-2,3-dihydro-1H-pyrrolizin-1-ol
• CAS: 26400-45-3
• 化学式: C₈H₁₁NO₂
• 分子量: 153.181
• InChiKey: QFPRRXUPCPFWKD-UHFFFAOYSA-N

物化性质

• 沸点：
  361.2±32.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  -1
• 重原子数：
  11
• 可旋转键数：
  1
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  45.4
• 氢给体数：
  2
• 氢受体数：
  2

安全信息

• 海关编码：
  2933990090

反应信息

• 作为反应物：
  描述：

  去氢倒千里光裂碱 以 甲醇 为溶剂， 生成 1-hydroxymethyl-7-methoxy-6,7-dihydro-5-H-pyrrolizine
  参考文献：
  名称：

  吡咯并立烷生物碱次生吡咯代谢物构建了多种激活途径，导致DNA加合物的形成和潜在的肝肿瘤的发生。

  摘要：

  吡咯嗪核生物碱（PAs）及其N-氧化物衍生物是肝毒性，遗传毒性和致癌性植物化学物质。PA通过一组四个（±）-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H介导的一般遗传毒性机制诱导肝肿瘤-吡咯烷嗪（DHP）衍生的DNA加合物。迄今为止，主要的吡咯代谢物脱氢PAs，它们的水解代谢物DHP和两个次要的吡咯代谢物7-谷胱甘肽-DHP（7-GS-DHP）和7-半胱氨酸-DHP是已知的能够产生这些DHP-DNA的代谢物在体内和/或在PA处理的细胞中形成加合物。次要的吡咯代谢物是由脱氢PA与谷胱甘肽，氨基酸和蛋白质的反应形成的。在这项研究中，我们确定了更多次生吡咯代谢物是否可以与小牛胸腺DNA和HepG2细胞中的细胞DNA结合，从而导致使用一系列次生吡咯代谢物（包括7-甲氧基-DHP， 9-乙氧基-DHP，9-缬氨酸-DHP，7-GS-DHP，7-半胱氨酸-DHP和7

  DOI：

  10.1021/acs.chemrestox.8b00096
• 作为产物：
  描述：

  (1R,4Z,6S,7R,17S)-4-ethylidene-7-hydroxy-6,7-dimethyl-2,9-dioxa-14-azatricyclo[9.5.1.014,17]heptadec-11-ene-3,8-dione 生成 去氢倒千里光裂碱
  参考文献：
  名称：

  WINTER, CARL K.;SEGALL, H. J.;JONES, A. DANIEL, BIOMED. AND ENVIRON. MASS SPECTROM., 15,(1988) N 5, 265-273

  摘要：

  DOI：

文献信息

• Reaction of Dehydropyrrolizidine Alkaloids with Valine and Hemoglobin
  作者：Yuewei Zhao、Shuguang Wang、Qingsu Xia、Gonçalo Gamboa da Costa、Daniel R. Doerge、Lining Cai、Peter P. Fu

  DOI：10.1021/tx5002139

  日期：2014.10.20

  Pyrrolizidine alkaloids exert toxicity through metabolism to dehydropyrrolizidine alkaloids that bind to cellular protein and DNA, leading to hepatotoxicity, genotoxicity, and tumorigenicity. To date, it is not clear how dehydropyrrolizidine alkaloids bind to cellular constituents, including amino acids and proteins, resulting in toxicity. Metabolism of carcinogenic monocrotaline, riddelliine, and heliotrine

  含吡咯烷定生物碱的植物可能是影响牲畜，野生动植物和人类的最常见的有毒植物。吡咯并立烷生物碱通过代谢作用作用于与细胞蛋白和DNA结合的脱氢吡咯并立烷生物碱，从而导致肝毒性，基因毒性和致瘤性。迄今为止，尚不清楚脱氢吡咯烷核生物碱如何与细胞成分（包括氨基酸和蛋白质）结合，从而导致毒性。致癌性单芥子碱，riddelliine和heliotrine的代谢分别产生脱氢单芥子碱，dehyroriddelliine和dehydroheliotrine，作为主要的反应性代谢产物。在这项研究中，我们报告说，脱氢单古田碱与缬氨酸的反应产生了四个高度不稳定的6,7-dihydro-7-hydroxy-1-hydroxymethyl-5 H-吡咯嗪（DHP）衍生的缬氨酸（DHP-缬氨酸）加合物。为了阐明结构，将DHP-缬氨酸加合物与异硫氰酸苯酯（PITC）衍生为DHP-缬氨酸-PITC产品。HPLC分离后，通过质谱，紫外可见分光光度法，1
• Human Liver Microsomal Metabolism and DNA Adduct Formation of the Tumorigenic Pyrrolizidine Alkaloid, Riddelliine
  作者：Qingsu Xia、Ming W. Chou、Fred. F. Kadlubar、Po-Cheun Chan、Peter P. Fu

  DOI：10.1021/tx025605i

  日期：2003.1.1

  obtained from rat liver microsomal metabolism. When metabolism was conducted in the presence of calf thymus DNA, the same set of eight DHP-derived DNA adducts was formed. Both the metabolism pattern and DNA adduct profile were very similar to those obtained from rat liver microsomes. When metabolism was conducted in the presence of the P450 3A4 enzyme inhibitor triacetyleandomycin, the formation of DHP and

  利得利宁是一种广泛存在的天然遗传毒性吡咯烷啶生物碱，在一项为期2年的NTP致癌生物测定法中，可在大鼠和小鼠中诱发肝脏肿瘤。我们已经确定，riddelliine通过遗传毒性机制诱导大鼠肝肿瘤，该机制涉及（+/-）-6,7-dihydro-7-hydroxy-1-hydroxymethyl-5H-pyrrolizine（DHP）的形成，该反应与DNA发生反应。形成一组八个DNA加合物。为了确定在实验动物中获得的结果与人的相关性，使用人肝微粒体进行了riddelliine的代谢。与大鼠肝微粒体一样，DHP和riddelliine N-氧化物是与人肝微粒体温育的主要代谢产物。DHP和riddelliine N-氧化物的水平分别为0.20-0.62和0.03-0.15 nmol / min / mg蛋白，与从大鼠肝脏微粒体代谢中获得的代谢物相当。当在小牛胸腺DNA的存在下进行新陈代谢时，会形成同一组
• WINTER, CARL K.;SEGALL, H. J.;JONES, A. DANIEL, BIOMED. AND ENVIRON. MASS SPECTROM., 15,(1988) N 5, 265-273
  作者：WINTER, CARL K.、SEGALL, H. J.、JONES, A. DANIEL

  DOI：——

  日期：——
• Multi-stage stem cell carcinogenesis
  申请人：Krtolica Ana

  公开号：US20100162416A1

  公开（公告）日：2010-06-24

  The present invention relates to a system of multi-stage stem cell carcinogenesis and a method of generating such multi-stage stem cell carcinogenesis system. Various stages of cancer stem cells can be generated from normal stem cells via mutagenesis. The system of the present invention enables monitoring changes in the ability of cells to transition from one stage of carcinogenesis to another and to identify genetic pathways and molecules that influence carcinogenesis. The present invention also enables a high-throughput and nonbiased screening for targets that preferentially affect cancer stem cells relative to non-cancer stem cells or their derivatives during stem cell carcinogenesis, thus is useful in developing anti-cancer therapeutics.
• [EN] MULTI-STAGE STEM CELL CARCINOGENESIS<br/>[FR] CARCINOGENESE DE CELLULES SOUCHES MULTIETAPES
  申请人：STEMLIFELINE INC

  公开号：WO2010037134A2

  公开（公告）日：2010-04-01

  The present invention relates to a system of multi-stage stem cell carcinogenesis and a method of generating such multi-stage stem cell carcinogenesis system. Various stages of cancer stem cells can be generated from normal stem cells via mutagenesis. The system of the present invention enables monitoring changes in the ability of cells to transition from one stage of carcinogenesis to another and to identify genetic pathways and molecules that influence carcinogenesis. The present invention also enables a high-throughput and nonbiased screening for targets that preferentially affect cancer stem cells relative to non-cancer stem cells or their derivatives during stem cell carcinogenesis, thus is useful in developing anti-cancer therapeutics.