methyl (1S,2R,3R,4aS,13bR,14aS)-2,11-dimethoxy-13-(prop-2-yn-1-yl)-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate | 1227009-32-6

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 育亨宾生物碱
• 英文名称: methyl (1S,2R,3R,4aS,13bR,14aS)-2,11-dimethoxy-13-(prop-2-yn-1-yl)-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate
• 英文别名: reserpine
• CAS: 1227009-32-6
• 化学式: C₃₆H₄₂N₂O₉
• 分子量: 646.737
• InChiKey: GHFDKWNBIFVAFA-WSFBGRJZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.28
• 重原子数：
  47.0
• 可旋转键数：
  9.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  106.92
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  methyl (1S,2R,3R,4aS,13bR,14aS)-2,11-dimethoxy-13-(prop-2-yn-1-yl)-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate 在 四甲基乙二胺 、 copper(l) chloride 作用下， 以 二氯甲烷 为溶剂， 反应 5.0h， 以43%的产率得到dimethyl 13,13'-(hexa-2,4-diyne-1,6-diyl)(1S,1'S,2R,2'R,3R,3'R,4aS,4a'S,13bR,13b'R,14aS,14a'S)-bis(2,11-dimethoxy-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,13,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate)
  参考文献：
  名称：

  高度对称的基于自然产品的开放式和封闭式结构的两种通用和并行方法

  摘要：

  报道了两种平行的方法，用于制备衍生自一系列单萜和二萜，类固醇和生物碱的多样且高度对称的杂种。两种方法均基于双（炔基）二锂试剂向具有羰基的天然产物中单加成生成相应的炔基衍生物。这些炔基天然产物单加合物的Glaser-Hay Cu促进的均偶联以及Huisgen Cu催化的叠氮化物-炔烃环加成（CuAAC）反应导致合成基于甾族，萜烯和生物碱的同质衍生物各种各样的间隔物来连接天然产物支架。

  DOI：

  10.1002/chem.200903264
• 作为产物：
  描述：

  利血平 、 3-溴丙炔 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 、 mineral oil 、 甲苯 为溶剂， 反应 1.25h， 以30%的产率得到methyl (1S,2R,3R,4aS,8aS,13bR,14aS)-2,11-dimethoxy-8a-(prop-2-yn-1-yl)-3-((3,4,5-trimethoxybenzoyl)oxy)-1,2,3,4,4a,5,7,8,8a,13b,14,14a-dodecahydroindolo[2',3':3,4]pyrido[1,2-b]isoquinoline-1-carboxylate
  参考文献：
  名称：

  高度对称的基于自然产品的开放式和封闭式结构的两种通用和并行方法

  摘要：

  报道了两种平行的方法，用于制备衍生自一系列单萜和二萜，类固醇和生物碱的多样且高度对称的杂种。两种方法均基于双（炔基）二锂试剂向具有羰基的天然产物中单加成生成相应的炔基衍生物。这些炔基天然产物单加合物的Glaser-Hay Cu促进的均偶联以及Huisgen Cu催化的叠氮化物-炔烃环加成（CuAAC）反应导致合成基于甾族，萜烯和生物碱的同质衍生物各种各样的间隔物来连接天然产物支架。

  DOI：

  10.1002/chem.200903264

文献信息

• Synthesis of Bioactive Complex Small Molecule–Ciprofloxacin Conjugates and Evaluation of Their Antibacterial Activity
  作者：Rahul Upadhyay、Rahul Kumar、Manoj Jangra、Rohit Rana、Onkar S. Nayal、Hemraj Nandanwar、Sushil K. Maurya

  DOI：10.1021/acscombsci.0c00060

  日期：2020.9.14

  Conjugates between pharmaceuticals and small molecules enable access to a vast chemical space required for the discovery of new lead molecules with modified therapeutic potential. However, the dearth of specific chemical reactions that are capable of functionalizing drugs and bioactive natural products presents a formidable challenge for preparing their conjugates. Here, we report a support-free CuI-nanoparticle-catalyzed strategy for conjugating electron-deficient and electron-rich terminal alkynes with a ciprofloxacin methyl ester. Our conjugation technique exploits the late-stage functionalization of bioactive natural products such as tocopherol, vasicinone, amino acids, and pharmaceuticals such as aspirin and paracetamol to provide conjugates in excellent yields under mild and green conditions. This protocol also enabled the synthesis of (hetero)arene-ciprofloxacin 1,4-disubstituted 1,2,3-triazoles in good yields and high regioselectivities. These synthesized ciprofloxacin conjugates were evaluated in vitro for their antibacterial activity against a panel of relevant bacteria. A significant number of conjugates showed comparable activity against Gram-positive and Gram-negative bacteria. Moreover, some conjugates exhibited less toxicity than ciprofloxacin against two mammalian cell lines, suggesting the utility for the future investigation of these compounds for in vivo efficacy and pharmacokinetic studies.