(1R,8R,9R,10S)-8-(4-bromophenyl)sulfanyl-3,4-dihydroxy-12-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one | 1361940-59-1

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (1R,8R,9R,10S)-8-(4-bromophenyl)sulfanyl-3,4-dihydroxy-12-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one
• CAS: 1361940-59-1
• 化学式: C₂₄H₂₄BrNO₄S
• 分子量: 502.429
• InChiKey: SGYHQTWTGTVYSO-KMBRJESTSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.3
• 重原子数：
  31
• 可旋转键数：
  3
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  95.3
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (1R,8R,9R,10S)-8-(4-bromophenyl)sulfanyl-3,4-dihydroxy-12-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one 、 乙酸酐 在 吡啶 作用下， 以87%的产率得到[(1R,8R,9R,10S)-3-acetyloxy-8-(4-bromophenyl)sulfanyl-12-methoxy-17-methyl-13-oxo-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-4-yl] acetate
  参考文献：
  名称：

  SINOMENINE DERIVATIVES, SYNTHETIC METHODS AND USES THEREOF

  摘要：

  该发明涉及青藤碱衍生物，其合成方法及应用。青藤碱衍生物包括氧化衍生物和C-10取代的青藤碱衍生物。基于青藤碱结构上易氧化的酚基团，可以利用氧化、氧化去芳香化或共轭加成芳香化来引入C-10取代基以合成青藤碱衍生物。该发明的青藤碱衍生物具有以下结构：通过体外TNF-α抑制实验，评估了合成化合物的活性。这些实验结果表明，大多数化合物具有抗炎作用，有些化合物的活性优于青藤碱。这些化合物可用于治疗类风湿性关节炎等免疫性疾病。

  公开号：

  US20120308589A1
• 作为产物：
  描述：

  盐酸青藤碱 在 碘苯二乙酸 作用下， 以 二氯甲烷 、 水 为溶剂， 反应 1.0h， 生成 (1R,8R,9R,10S)-8-(4-bromophenyl)sulfanyl-3,4-dihydroxy-12-methoxy-17-methyl-17-azatetracyclo[7.5.3.01,10.02,7]heptadeca-2(7),3,5,11-tetraen-13-one
  参考文献：
  名称：

  SINOMENINE DERIVATIVES, SYNTHETIC METHODS AND USES THEREOF

  摘要：

  该发明涉及青藤碱衍生物，其合成方法及应用。青藤碱衍生物包括氧化衍生物和C-10取代的青藤碱衍生物。基于青藤碱结构上易氧化的酚基团，可以利用氧化、氧化去芳香化或共轭加成芳香化来引入C-10取代基以合成青藤碱衍生物。该发明的青藤碱衍生物具有以下结构：通过体外TNF-α抑制实验，评估了合成化合物的活性。这些实验结果表明，大多数化合物具有抗炎作用，有些化合物的活性优于青藤碱。这些化合物可用于治疗类风湿性关节炎等免疫性疾病。

  公开号：

  US20120308589A1

文献信息

• Regio- and stereoselective C10β–H functionalization of sinomenine: an access to more potent immunomodulating derivatives
  作者：Yang-Tong Lou、Li-Yan Ma、Meng Wang、Dongsheng Yin、Ting-Ting Zhou、Ai-Zhong Chen、Zhao Ma、Chao Bian、Shaozhong Wang、Zhen-Yu Yang、Bing Sun、Zhu-Jun Yao

  DOI：10.1016/j.tet.2012.01.009

  日期：2012.3

  Regio- and stereoselective C-10 beta-H functionalization of sinomenine, an economically available natural immunomodulating alkaloid, has been studied, developed and successfully applied to the synthesis of new immunosuppressive sinomenine derivatives in a protecting-free fashion. Regioselective oxidation of sinomenine with (diacetoxylodo)benzene (DIB) in water provided a single stable benzoquinone derivative 4, and subsequent 1,6-conjugated addition of 4 with alcohols, amines, and thiols afforded a new series of C-10 beta-H functionalized sinomenine derivatives stereoselectively. Some derivatives with a newly introduced 10 beta-bezenesulfanyl substituent exhibited much higher TNF-alpha inhibitory potency than their natural parent sinomenine. This work opens a convenient access to novel sinomenine derivatives with medicinal interests. (C) 2012 Elsevier Ltd. All rights reserved.
• US8557837B2
  申请人：——

  公开号：US8557837B2

  公开（公告）日：2013-10-15
• SINOMENINE DERIVATIVES, SYNTHETIC METHODS AND USES THEREOF
  申请人：Yao Zhujun

  公开号：US20120308589A1

  公开（公告）日：2012-12-06

  The invention relates to sinomenine derivatives, methods for their synthesis and their applications. The sinomenine derivatives include oxidation derivatives, and C-10 substituted sinomenine derivatives. Based on the readily oxidizable phenol group on sinomenine structure, using oxidation, oxidative dearomatization, or conjugated addition aromatization, one can introduce C-10 substitutions to synthesize the sinomenine derivatives. The sinomenine derivatives of the invention have the following structures: Using in vitro TNF-α inhibition assay, the activities of the synthetic compounds are assessed. Results from these assays shown that most compounds have anti-inflammatory effects, and some compounds have better activities than that of sinomenine. These compounds may be used in treating immune diseases such as rheumatoid arthritis (RA).

  该发明涉及青藤碱衍生物，其合成方法及应用。青藤碱衍生物包括氧化衍生物和C-10取代的青藤碱衍生物。基于青藤碱结构上易氧化的酚基团，可以利用氧化、氧化去芳香化或共轭加成芳香化来引入C-10取代基以合成青藤碱衍生物。该发明的青藤碱衍生物具有以下结构：通过体外TNF-α抑制实验，评估了合成化合物的活性。这些实验结果表明，大多数化合物具有抗炎作用，有些化合物的活性优于青藤碱。这些化合物可用于治疗类风湿性关节炎等免疫性疾病。