6-methoxy-5,6-dihydrochelerythrine | 21080-31-9

• 物质功能分类: 有机原料
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 苯并菲啶生物碱
• 英文名称: 6-methoxy-5,6-dihydrochelerythrine
• 英文别名: 12,13-dihydro-13-methoxychelerythrine；6-methoxyldihydrochelerythrine；6-methoxydihydrochelerythrine；8-methoxydihydrochelerythrine；angoline；1,2,13-trimethoxy-12-methyl-13H-[1,3]benzodioxolo[5,6-c]phenanthridine
• CAS: 21080-31-9
• 化学式: C₂₂H₂₁NO₅
• 分子量: 379.412
• InChiKey: LVWAKZBZWYHYCJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.27
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

安全信息

• 储存条件：
  储存条件：2-8°C，避免光线直射，保持干燥并密封。

制备方法与用途

生物活性

Angoline 是一种有效的选择性 IL6/STAT3 信号通路抑制剂，其IC50值为11.56 μM。该化合物能够抑制 STAT3 的磷酸化及其靶基因的表达，并进而抑制癌细胞的增殖。

靶点

• IC50: 11.56 μM (IL6/STAT3信号通路)

反应信息

• 作为反应物：
  描述：

  6-methoxy-5,6-dihydrochelerythrine 、 异丙醇 反应 2.0h， 以45%的产率得到6-isopropoxy-5,6-dihydrochelerythrine
  参考文献：
  名称：

  WO2008/16596

  摘要：

  公开号：
• 作为产物：
  描述：

  氧基白屈菜季铵碱 在 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 生成 6-methoxy-5,6-dihydrochelerythrine
  参考文献：
  名称：

  小ber碱仿生转化为白屈菜红碱和二氢白屈菜红碱

  摘要：

  通过生物发生途径开发了一种由黄连素合成新颖高效的苯并[ c ]菲啶生物碱，白屈菜红碱和二氢白屈菜红碱的方法。

  DOI：

  10.1039/c39840000718

文献信息

• In Vitro Antifungal Activity of Sanguinarine and Chelerythrine Derivatives against Phytopathogenic Fungi
  作者：Xin-Juan Yang、Fang Miao、Yao Yao、Fang-Jun Cao、Rui Yang、Yan-Ni Ma、Bao-Fu Qin、Le Zhou

  DOI：10.3390/molecules171113026

  日期：——

  In order to understand the antifungal activity of some derivatives of sanguinarine (S) and chelerythrine (C) and their structure-activity relationships, sixteen derivatives of S and C were prepared and evaluated for in vitro antifungal activity against seven phytopathogenic fungi by the mycelial growth rate method. The results showed that S, C and their 6-alkoxy dihydro derivatives S1–S4, C1–C4 and 6-cyanodihydro derivatives S5, C5 showed significant antifungal activity at 100 µg/mL against all the tested fungi. For most tested fungi, the median effective concentrations of S, S1, C and C1 were in a range of 14–50 µg/mL. The structure-activity relationship showed that the C=N+ moiety was the determinant for the antifungal activity of S and C. S1–S5 and C1–C5 could be considered as the precursors of S and C, respectively. Thus, the present results strongly suggested that S and C or their derivatives S1–S5 and C1–C5 should be considered as good lead compounds or model molecules to develop new anti-phytopathogenic fungal agents.

  为了理解血根碱（S）和白屈菜红碱（C）及其衍生物的抗真菌活性和结构-活性关系，制备并评估了十六种S和C衍生物对七种植物病原真菌的体外抗真菌活性，采用菌丝生长速率法进行测定。结果显示，S、C及其6-烷氧基二氢衍生物S1-S4、C1-C4和6-氰基二氢衍生物S5、C5在100 µg/mL浓度下对所有测试真菌均表现出显著的抗真菌活性。对于大多数测试真菌，S、S1、C和C1的中效浓度范围为14-50 µg/mL。结构-活性关系表明，C=N+部分是S和C抗真菌活性的决定因素。S1-S5和C1-C5可以分别被视为S和C的前体。因此，当前结果强烈表明，S和C或其衍生物S1-S5和C1-C5应被视为开发新型抗植物病原真菌剂的优良先导化合物或模型分子。
• Structural Modification of Sanguinarine and Chelerythrine and Their <i>in Vitro</i> Acaricidal Activity against <i>Psoroptes cuniculi</i>
  作者：Fang Miao、Xin-Juan Yang、Yan-Ni Ma、Feng Zheng、Xiao-Ping Song、Le Zhou

  DOI：10.1248/cpb.c12-00618

  日期：——

  Sanguinarine (1) and chelerythrine (2) are two quaternary benzo[c]phenanthridine alkaloids (QBAs). Eighteen derivatives of 1 and 2 were synthesized by modification of C=N+ bond and evaluated for their in vitro acaricidal activity against Psoroptes cuniculi, a mange mite. A new method was developed to prepare 6-alkoxy dihydro derivatives of 1 and 2 (1a–e, 2a–e). Among all the compounds, only 6-alkoxy dihydrosanguinarines (1a–e) showed significant acaricidal activity at 5.0 mg/mL and 1a possessed the strongest activity (50% lethal concentrations (LC50)=339.70±0.75 mg/L, 50% lethal time (LT50)=6.53±0.04 h), comparable with a standard drug ivermectin (LC50=168.19±11.79 mg/L, LT50=16.54±0.11 h). The iminium moiety in 1 and 2 was proven to be the determinant for their acaricidal properties. 6-Alkoxy dihydro derivatives (1a–e, 2a–e) were prodrugs of 1 and 2. Compared with 7,8-dimethoxy groups, 7,8-methylenedioxy group was able to significantly improve the bioactivity. The present results suggested that QBAs are promising candidates or lead compounds for the development of new isoquinoline acaricidal agents.

  血根碱（1）和白屈菜红碱（2）是两种季铵基苯并[c]菲啶生物碱（QBAs）。通过C=N+键的修饰合成了1和2的18个衍生物，并评估了它们对兔耳螨（Psoroptes cuniculi）的体外杀螨活性。开发了一种新方法制备1和2的6-烷氧基二氢衍生物（1a–e，2a–e）。在所有化合物中，只有6-烷氧基二氢血根碱（1a–e）在5.0 mg/mL浓度下显示出显著的杀螨活性，其中1a具有最强的活性（50%致死浓度（LC50）=339.70±0.75 mg/L，50%致死时间（LT50）=6.53±0.04 h），与标准药物伊维菌素（LC50=168.19±11.79 mg/L，LT50=16.54±0.11 h）相当。1和2中的亚胺基团被证实是其杀螨活性的决定因素。6-烷氧基二氢衍生物（1a–e，2a–e）是1和2的前药。与7,8-二甲氧基相比，7,8-甲基二氧基能显著提高生物活性。现有结果表明，QBAs是有前景的候选化合物或开发新型异喹啉杀螨剂的先导化合物。
• Fluorescence, Absorption, Chromatography and Structural Transformation of Chelerythrine and Ethoxychelerythrine in Protic Solvents: A Comparative Study
  作者：Jinjin Cao、Yanhui Zheng、Ting Liu、Jiamiao Liu、Jinze Liu、Jing Wang、Qirui Sun、Wenhong Li、Yongju Wei

  DOI：10.3390/molecules27154693

  日期：——

  reference substances for quality control of Chinese herbal medicines, and ECH is the dihydrogen derivative of CH. In this study, their fluorescence and absorption spectra, as well as their structural changes in different protic solvents were compared. It was observed that their emission fluorescence spectra in methanol were almost the same (both emitted at 400 nm), which may be attributed to the nucleophilic

  白屈菜红碱（CH）和乙氧基白屈菜红碱（ECH）是中草药质量控制的化学对照品，ECH是CH的二氢衍生物。在这项研究中，比较了它们的荧光和吸收光谱，以及它们在不同质子溶剂中的结构变化。观察到它们在甲醇中的发射荧光光谱几乎相同（均在 400 nm 处发射），这可能是由于 CH 和 ECH 与甲醇分子发生亲核和交换反应，共同生成 6-甲氧基-5， 6-二氢白屈菜红碱 (MCH)。加水稀释后，MCH转化为CH，主要以带正电荷的CH +形式存在在酸性和近中性条件下，荧光发射波长为 550 nm。随着水溶液pH值的升高，CH +转化为6-羟基-5,6-二氢白屈菜红碱(CHOH)，在410 nm处发出荧光。MCH和CHOH的荧光量子产率分别为0.13和0.15，两者的荧光强度都远强于CH +。得出CH和ECH在同一质子溶剂中可以相互替代的结论，并通过高效液相色谱进一步验证。本研究将有助于对苯并菲啶类生物碱
• Structural modification of sanguinarine and chelerythrine and their antibacterial activity
  作者：Fang Miao、Xin-Juan Yang、Le Zhou、Hai-Jun Hu、Feng Zheng、Xu-Dong Ding、Dong-Mei Sun、Chun-Dong Zhou、Wei Sun

  DOI：10.1080/14786419.2010.482055

  日期：2011.5

  In this study, five derivatives of sanguinarine (1) and chelerythrine (2) were prepared, with 1 and 2 as starting materials, by reduction, oxidation and nucleophilic addition to the iminium bond C=N+. The structures of all compounds were elucidated on account of their MS, 1H-NMR and 13C-NMR data. The antibacterial activities of all compounds were screened, using Staphylococcus aureus, Escherichia coli, Aeromonas hydrophila and Pasteurella multocida as test bacteria. The minimum bacteriostatic concentration and minimum bactericidal concentration of the active compounds were determined by the turbidity method. The structure-activity relationships of 1 and 2 were discussed. The results showed that 1, 2 and their pseudoalcoholates were found to be potent inhibitors to S. aureus, E. coli and A. hydrophila, while the other derivatives were found to be inactive. The pseudoalcoholates might be the prodrugs of 1 and 2. The iminium bond in the molecules of 1 or 2 was the determinant for antibacterial activity, and the substituents at the 7 and 8 positions influenced the antibacterial activities of 1 and 2 against different bacteria.
• Hanaoka, Miyoji; Motonishi, Toshio; Mukai, Chisato, Journal of the Chemical Society. Perkin transactions I, 1986, p. 2253 - 2256
  作者：Hanaoka, Miyoji、Motonishi, Toshio、Mukai, Chisato

  DOI：——

  日期：——