二氢黄连碱 | 53777-78-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 原小檗碱生物碱及其衍生物
• 中文名称: 二氢黄连碱
• 英文名称: dihydrocoptisine
• 英文别名: 5,7,17,19-Tetraoxa-13-azahexacyclo[11.11.0.02,10.04,8.015,23.016,20]tetracosa-1(24),2,4(8),9,15(23),16(20),21-heptaene
• CAS: 53777-78-9
• 化学式: C₁₉H₁₅NO₄
• 分子量: 321.332
• InChiKey: FYTDXOGJMXIITH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  24
• 可旋转键数：
  0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.26
• 拓扑面积：
  40.2
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  二氢黄连碱 在 盐酸 作用下， 以 乙醇 、 水 为溶剂， 反应 5.0h， 生成 紫堇沙明碱
  参考文献：
  名称：

  Syntheses and structure–activity relationships in cytotoxicities of 13-substituted quaternary coptisine derivatives

  摘要：

  Twenty five 13-substituted quaternary coptisine derivatives were synthesized to test their cytotoxicities against several cancer cell-lines and on intestinal epithelial cell-6 (IEC-6) in vitro to evaluate structure-activity relationship (SAR). Introduction of the alkyl groups into the C-13 position of quaternary coptisine (1) led to significant increase of the cytotoxic activity, while the substitution of arylmethyl groups and others at the same position showed no effect on improving cytotoxicities against the same cancer cell-lines. The cytotoxicities of quaternary 13-alkylcoptisines was significantly reinforced as the length of the aliphatic chain increased, with quaternary 13-n-undecylcoptisine (4l) showing 7, 23, 12, and 9 times, respectively, more active than quaternary coptisine (1) against HCT, A549, Be17402, and C33A, and being 4, 11, 2, and 3 times, respectively, more active than the positive control, fluorouracil (5-FU), against the same cell-lines, by IC50 values. In comparison to quaternary 13-n-undecylcoptisine (4l) and the above references, quaternary 13-n-dodecylcoptisine (4m) almost showed the same cytotoxicities. In contrast with the n-alkyl chains, the arylmethyl substituents at C-13 displayed low cytotoxicity, except for naphthyl rings or phenyl rings with CF3 or methyl substituents. However, their low cytotoxicity could make them useful as drug candidates for other diseases (bowel, etc). (C) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.09.006
• 作为产物：
  描述：

  N-methyl-13,14-dehydrostylopinium chloride 生成 二氢黄连碱
  参考文献：
  名称：

  Haworth; Perkin, Journal of the Chemical Society, 1926, p. 1776

  摘要：

  DOI：

文献信息

• Derivatives Of Protoberberine Biological Alkaloids And Use Of Same Inhibiting Ulcerative Colitis
  申请人：Institute of Materia Medica, Chinese Academy of Medical Sciences

  公开号：US20150031717A1

  公开（公告）日：2015-01-29

  Disclosed are derivatives of protoberberine biological alkaloids or physiologically acceptable salts thereof produced by means of a derivative reaction of a source material of biological alkaline quaternary ammonium salts of protoberberine alkaloids, a preparation method for same and pharmaceutical uses thereof. The derivatives of protoberberine biological alkaloids or the physiologically acceptable salts thereof show activity inhibiting ulcerative colitis and can be used in the preparation of drugs for same.

  本文披露了通过对原生物碱类季铵盐的源材料进行衍生反应而产生的原生物碱类季铵盐的衍生物或其生理上可接受的盐，以及其制备方法和药用用途。原生物碱类季铵盐的衍生物或其生理上可接受的盐显示出抑制溃疡性结肠炎的活性，并可用于制备相应药物。
• Versatile methods for synthesizing organic acid salts of quaternary berberine-type alkaloids as anti-ulcerative colitis agents
  作者：Zhi-Hui Zhang、Jing Li、Hai-Jing Zhang、An-Jun Deng、Lian-Qiu Wu、Zhi-Hong Li、Hong-Rui Song、Wen-Jie Wang、Hai-Lin Qin

  DOI：10.1080/10286020.2016.1171760

  日期：2016.6.2

  Two versatile methods to synthesize kinds of organic acid salts of quaternary berberine-type alkaloids were investigated in order to determine which is more efficient to improve the liposolubility of the target compounds and to explore the efficacy of the target compounds as anti-ulcerative colitis (UC) agents. Overall evaluation according to the reaction results and yields of the final products indicated

  为了确定哪种更有效地改善目标化合物的脂溶性和探索目标化合物作为抗溃疡性结肠炎（UC）的功效，研究了两种通用的方法来合成季铵盐小ber碱型生物碱的各种有机酸盐。 ）代理商。根据反应结果和最终产物的收率进行的总体评价表明，使用叔（±）-8-酰基甲基二氢小ber碱型生物碱作为关键中间体的合成方法优于使用叔二氢小ber碱型生物碱作为中间体的合成方法。分别以氯化小and碱氯化物和氯化黄连磷酸碱为起始原料合成了十种目标化合物，并使用双重荧光素酶报告基因检测技术在体外x-box结合蛋白1（XBP1）转录活性测定中评估了某些目标化合物的抗UC活性。在10μM的条件下，发现受测化合物可激活XBP1靶标的转录，其转录水平几乎与季铵化黄连的水平相同。还发现合成的目标化合物比季铵小ber碱型生物碱的无机酸盐具有更高的脂溶性。
• A General, Concise Strategy that Enables Collective Total Syntheses of over 50 Protoberberine and Five Aporhoeadane Alkaloids within Four to Eight Steps
  作者：Shiqiang Zhou、Rongbiao Tong

  DOI：10.1002/chem.201601245

  日期：2016.5.17

  reported. This synthesis represents the most efficient and shortest route to date, featuring three catalytic processes: CuI‐catalyzed redox‐A3 reaction, Pd‐catalyzed reductive carbocyclization, and PtO2‐catalyzed hydrogenation. Importantly, this new strategy to the tetracyclic framework has also been applied to the collective concise syntheses of >30 natural protoberberines (without 13‐methyl group) and

  报告了一种简洁，催化和通用的策略，该策略允许在四个步骤中为每个分子高效地合成22种天然13-甲基原小ber碱。该合成代表了迄今为止最有效，最短的路线，具有三个催化过程：CuI催化的氧化还原A 3反应，Pd催化的还原碳环化和PtO 2催化的氢化。重要的是，这种针对四环框架的新策略也已应用于30多种天然原小ber碱（无13-甲基）和5种金刚烷烷生物碱的集体简明合成中。
• Convenient Synthesis of 2,3,9,10-Tetraoxygenated Protoberberine Alkaloids and their 13-Methyl Alkaloids.
  作者：Miyoji HANAOKA、Taeko HIRASAWA、Won Jea CHO、Shingo YASUDA

  DOI：10.1248/cpb.48.399

  日期：——

  New and convenient synthesis of 2,3,9,10-tetraoxygenated protoberberine alkaloids and their 13-methyl alkaloids through the same intermediates was developed. Acylation of the brominated benzylphenethylamine (13) with alpha-chloro-alpha-(methylthio)acetyl chloride, followed by cyclization with stannic chloride, furnished the key intermediates 4-methylthio-3-phenethylisoquinolin-3-ones (14), which were

  开发了通过同一中间体合成2,3,9,10-四氧合原小ber碱生物碱及其13-甲基生物碱的新方法。将溴化苄基苯乙胺（13）与α-氯-α-（甲硫基）乙酰氯酰化，然后与氯化锡环化，提供了关键中间体4-甲硫基-3-苯乙基异喹啉-3-酮（14），将其甲基化提供其甲基衍生物（17）。异喹啉-3-酮（14、17）都容易以高收率转化为原小ber碱生物碱（16）及其13-甲基生物碱（21）。
• A Unified Strategy for the Syntheses of the Isoquinolinium Alkaloids Berberine, Coptisine, and Jatrorrhizine
  作者：Luis M. Mori-Quiroz、Sidnee L. Hedrick、Andrew R. De Los Santos、Michael D. Clift

  DOI：10.1021/acs.orglett.8b01702

  日期：2018.7.20

  Total syntheses of the antibacterial alkaloids berberine, coptisine, and jatrorrhizine have been achieved in four steps through a unified route. The key step of this strategy is an efficient intramolecular Friedel–Crafts alkoxyalkylation which, following oxidation, establishes the isoquinolinium core of these natural products. Herein, the design and development of this synthetic strategy, which has

  抗菌生物碱小ber碱，黄连碱和麻风树碱的总合成已通过一条统一的路线通过四个步骤完成。该策略的关键步骤是有效的分子内Friedel-Crafts烷氧基烷基化反应，该反应在氧化后建立了这些天然产物的异喹啉鎓核心。在本文中，描述了这种合成策略的设计和开发，该合成策略使得迄今报道的这些生物碱的最短和最有效的合成成为可能。