青藤碱N-氧化物 | 1000026-77-6

• 物质功能分类: 生物化工 - 提取物 - 植物提取物
• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 中文名称: 青藤碱N-氧化物
• 中文别名: 青藤碱N氧化物
• 英文名称: sinomenine N-oxide
• 英文别名: (1R,9S,10S)-3-hydroxy-4,12-dimethoxy-17-methyl-17-oxido-17-azoniatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one
• CAS: 1000026-77-6
• 化学式: C₁₉H₂₃NO₅
• 分子量: 345.395
• InChiKey: IQCNMIIBBLJCAC-SLAUIZBQSA-N

物化性质

• 熔点：
  155-156 °C(Solv: methanol (67-56-1))

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  25
• 可旋转键数：
  2
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  73.8
• 氢给体数：
  1
• 氢受体数：
  5

制备方法与用途

青藤碱氮氧化物具有抗血管生成、抗炎和抗风湿作用。此外，它也是一种NO生成抑制剂，IC50值为23.04μM。

反应信息

• 作为反应物：
  描述：

  青藤碱N-氧化物 在 FAD 、 还原型辅酶Ⅰ 作用下， 以 aq. phosphate buffer 为溶剂， 反应 2.0h， 生成 青藤碱
  参考文献：
  名称：

  Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide

  摘要：

  Aims: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO.Materials and methods: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN'S metabolites. Enzymatic and nonenzymatic incubations were used to reveal SIN'S metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-kappa B were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 mu M) was also assessed.Key findings: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-alpha and nuclear translocation of NF-kappa B were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 mu M. In contrast, SNO induced ROS production.Significance: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.

  DOI：

  10.1016/j.lfs.2020.118433
• 作为产物：
  描述：

  青藤碱 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 0.5h， 以76%的产率得到青藤碱N-氧化物
  参考文献：
  名称：

  通过[Mn（TDCPP）Cl]催化的N胺化反应，从天然脂肪族叔生物碱（R3N）直接制备未保护的氨基酰亚胺（R3N + -NH-）。

  摘要：

  天然脂肪族叔胺生物碱的面板（R 3 N）直接转化为R 3 Ñ + -NH - （无需制备保护的胺化酰亚胺- [R 3 Ñ + -NR' -接着脱保护）由[Mn（上TDCPP）氯在温和的反应条件下，以O-（2,4-二硝基苯基）羟胺为氮源，经[ - ]催化的N-胺化反应，收率高达98％。

  DOI：

  10.1039/d0cc02934c

文献信息

• Synthesis and biological evaluation of unique stereodimers of sinomenine analogues as potential inhibitors of NO production
  作者：Peng Teng、Hai-Liang Liu、Zhang-Shuang Deng、Zhi-Bing Shi、Yun-Mian He、Li-Li Feng、Qiang Xu、Jian-Xin Li

  DOI：10.1016/j.bmc.2011.04.006

  日期：2011.5

  production has been recognized as a potential means for the treatment of rheumatoid arthritis (RA). In order to discover more potent inhibitors and explore the preliminary structure activity relationship, a series of unique stereodimers of sinomenine analogues were designed and synthesized. Their inhibitory activity on NO production and cytotoxicity were evaluated using LPS-activated murine macrophages

  抑制过量NO的产生已被认为是治疗类风湿关节炎（RA）的潜在手段。为了发现更多有效的抑制剂并探索初步的结构活性关系，设计并合成了一系列独特的青藤碱类似物立体异构体。分别使用LPS激活的鼠巨噬细胞RAW264.7测定法和MTT方法评估了它们对NO产生的抑制活性和细胞毒性。在这些化合物中，1A，2，图2a，图2b，和4显示出对NO产生有效的抑制活性无明显的细胞毒性。此外，2，图2a和2b中显着抑制iNOS的mRNA表达。有趣的是，（S）-二聚体显示出比（R）-二聚体更好的生物活性。这些化合物可以作为RA治疗的新型治疗药物开发中的主要候选药物。
• Access to a Structurally Complex Compound Collection via Ring Distortion of the Alkaloid Sinomenine
  作者：Alfredo Garcia、Bryon S. Drown、Paul J. Hergenrother

  DOI：10.1021/acs.orglett.6b02333

  日期：2016.10.7

  Many compound collections used in high-throughput screening are composed of members whose structural complexity is considerably lower than that of natural products. We previously reported a strategy for the synthesis of complex and diverse small molecules from natural products using ring-distortion reactions, called complexity-to-diversity (CtD), and herein, CtD is applied in the synthesis of 16 diverse

  许多用于高通量筛选的化合物集合由结构复杂性远低于天然产物的成员组成。我们之前报道了一种利用环畸变反应从天然产物中合成复杂多样的小分子的策略，称为复杂性到多样性（CtD），在这里，CtD被应用于合成16种不同的支架和65种总化合物来自生物碱天然产物青藤碱。化学信息分析表明这些化合物具有复杂的环系和明显的三维性。
• Morphinane Alkaloids with Cell Protective Effects from <i>Sinomenium </i><i>a</i><i>cutum</i>
  作者：Guan-Hu Bao、Guo-Wei Qin、Rui Wang、Xi-Can Tang

  DOI：10.1021/np050112+

  日期：2005.7.1

  One new morphinane alkaloid, sinomenine N-oxide (1), and one new natural occurring morphinane alkaloid, N-demethylsinomenine (2), together with six known alkaloids, 7,8-didehydro-4-hydroxy-3,7-dimethoxymorphinan-6-ol (3), sinomenine (4), sinoacutine (5), N-norsinoacutine, acutumine, and acutumidine, were isolated from the stems of Sinomenium acutum. Their structures were elucidated on the basis of spectroscopic analysis and chemical methods. Compounds 2, 3, and 5 have protective effects against hydrogen peroxide-induced cell injury.
• Metabolic mechanism and anti-inflammation effects of sinomenine and its major metabolites N-demethylsinomenine and sinomenine-N-oxide
  作者：Qiang Li、Wenbin Zhou、Yuyan Wang、Fang Kou、Chunming Lyu、Hai Wei

  DOI：10.1016/j.lfs.2020.118433

  日期：2020.11

  Aims: Sinomenine (SIN) is clinically used as an anti-rheumatic drug. However, the metabolic and pharmacological mechanisms of SIN combined with its metabolites are unclear. This study aims to explore the cyclic metabolic mechanism of SIN, the anti-inflammation effects of SIN and its major metabolites (N-demethylsinomenine (DS) and sinomenine-N-oxide (SNO)), and the oxidation property of SNO.Materials and methods: SIN was administrated to rats via gavage. Qishe pills (a SIN-containing drug) were orally administrated to humans. The bio-samples were collected to identify SIN'S metabolites. Enzymatic and nonenzymatic incubations were used to reveal SIN'S metabolic mechanism. Impacts of SIN, SNO and DS on the inflammation-related cytokine's levels and nuclear translocation of NF-kappa B were evaluated in LPS-induced Raw264.7 cells. ROS induced by SNO (10 mu M) was also assessed.Key findings: CYP3A4 and ROS predominantly mediated the formation of SNO, and CYP3A4 and CYP2C19 primarily mediated the formation of DS. Noteworthily, SNO underwent N-oxide reduction both enzymatically, by xanthine oxidase (XOD), and non-enzymatically, by ferrous ion and heme moiety. The levels of IL-6 and TNF-alpha and nuclear translocation of NF-kappa B were ameliorated after pretreatment of SIN in LPS-induced Raw264.7 cells, while limited attenuations were observed after pretreatment of DS (SNO) even at 200 mu M. In contrast, SNO induced ROS production.Significance: This study elucidated that SIN underwent both enzymatic and non-enzymatic cyclic metabolism and worked as the predominant anti-inflammation compound, while SNO induced ROS production, suggesting more studies of SIN combined with SNO and DS are necessary in case of DDI and potential toxicities.
• Direct preparation of unprotected aminimides (R₃N⁺–NH⁻) from natural aliphatic tertiary alkaloids (R₃N) by [Mn(TDCPP)Cl]-catalysed <i>N</i>-amination reaction
  作者：Shilong Zhang、Yungen Liu、Fangrong Xing、Chi-Ming Che

  DOI：10.1039/d0cc02934c

  日期：——

  alkaloids (R3N) were directly converted to R3N+–NH− (without the need to prepare protected aminimides R3N+–NR′− followed by deprotection) by [Mn(TDCPP)Cl]-catalysed N-amination reaction, with O-(2,4-dinitrophenyl)hydroxylamine as the nitrogen source, in up to 98% yields under mild reaction conditions.

  天然脂肪族叔胺生物碱的面板（R 3 N）直接转化为R 3 Ñ + -NH - （无需制备保护的胺化酰亚胺- [R 3 Ñ + -NR' -接着脱保护）由[Mn（上TDCPP）氯在温和的反应条件下，以O-（2,4-二硝基苯基）羟胺为氮源，经[ - ]催化的N-胺化反应，收率高达98％。