(S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydrobenzo[a]heptalen-9(5H)-one | 1233709-95-9

• 分子结构分类: 有机化合物 - 碳氢化合物衍生物 - 环庚三烯酮
• 英文名称: (S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydrobenzo[a]heptalen-9(5H)-one
• 英文别名: (aR,7S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydrobenzo[a]heptalene-9(5H)-one；(7S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydro-5H-benzo[a]heptalen-9-one
• CAS: 1233709-95-9
• 化学式: C₂₀H₂₁N₃O₅
• 分子量: 383.404
• InChiKey: DERGXRKHZDDPAH-AWEZNQCLSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  68.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydrobenzo[a]heptalen-9(5H)-one 在 sodium 作用下， 以 甲醇 为溶剂， 以54%的产率得到(aR,5S)-methyl azido-9,10,11-trimethoxy-6,7-dihydro-5H-dibenzo[a,c][7]annulene-3-carboxylate
  参考文献：
  名称：

  A Convenient Entry to New C-7-Modified Colchicinoids through Azide Alkyne [3+2] Cycloaddition: Application of Ring-Contractive Rearrangements

  摘要：

  Reliable procedures for the preparation of azides derived from colchicine (1), allocolchicine (3) and N-acetylcolchinol (4a) were developed. These azides were then employed in Cu-catalyzed Huisgen-Sharpless [3+2] cycloaddition ("click") reactions with alkynes under microwave irradiation. The method developed opens a convenient and efficient access to libraries of new C-7-modified colchicinoids (triazole derivatives). In addition, a plausible mechanistic rationale for the colchicine-allocolchicine rearrangement is suggested.

  DOI：

  10.3987/com-10-s(e)117
• 作为产物：
  描述：

  秋水仙碱 在 4-二甲氨基吡啶 、 fluorosulfuryl azide 、 sodium methylate 、 potassium hydrogencarbonate 、 N,N-二异丙基乙胺 、 三氟乙酸 作用下， 以 甲醇 、 甲基叔丁基醚 、 水 、 二甲基亚砜 、 乙腈 为溶剂， 反应 0.5h， 生成 (S)-7-azido-1,2,3,10-tetramethoxy-6,7-dihydrobenzo[a]heptalen-9(5H)-one
  参考文献：
  名称：

  用于合成芳基氮并三唑光开关的偶氮乙炔

  摘要：

  我们报告了一种针对新型芳基氮并三唑光开关及其光物理特性的模块化方法。锂化 TIPS-乙炔与芳基重氮四氟硼酸盐的加成得到范围广泛的偶氮乙炔，构成了一类尚未开发的稳定中间体。原位脱硅瞬时导致末端芳基偶氮乙炔发生铜催化环加成反应 (CuAAC)，并产生多种有机叠氮化物。这些包括源自天然产物或药物的复杂分子，例如秋水仙碱、紫杉醇、达菲和花生四烯酸。芳基氮并三唑显示近定量光异构化和长热Z-半条命。使用该方法，我们首次介绍了联乙炔平台的设计和合成。它允许实施连续和面向多样性的方法，将两种不同的偶联物连接到一个常见的光开关偶氮三唑中的独立可寻址乙炔。这在几种光开关偶联物的合成中得到了展示，具有作为 photoPROTAC 和生物素偶联物的潜在应用。

  DOI：

  10.1021/jacs.1c06014

文献信息

• Colchicine metallocenyl bioconjugates showing high antiproliferative activities against cancer cell lines
  作者：Karolina Kowalczyk、Andrzej Błauż、Wojciech M. Ciszewski、Anna Wieczorek、Błażej Rychlik、Damian Plażuk

  DOI：10.1039/c7dt03229c

  日期：——

  A series of ferrocenyl and ruthenocenyl conjugates with colchicine bearing a 1,2,3-triazole moiety were synthesized and their anticancer properties were evaluated. We found that the most potent metallocenyl derivatives Rc4 and Rc5 are 6–7 times more cytotoxic toward HepG2 cells, while Fc4 and Fc5 are two times more cytotoxic toward HCT116 cells as colchicine. We also found that compounds Fc4, Fc5,

  合成了带有带有1,2,3-三唑部分秋水仙碱的一系列二茂铁基和钌烯基共轭物，并评估了它们的抗癌性能。我们发现最有效的茂金属衍生物Rc4和Rc5对HepG2细胞的细胞毒性是秋水仙碱的6-7倍，而Fc4和Fc5对HCT116细胞的细胞毒性是其两倍。我们还发现，化合物Fc4，Fc5，Rc1和Rc3–Rc5能够诱导凋亡，而化合物Fc2则可以阻止有丝分裂。
• A Bioorthogonal Small Molecule Selective Polymeric “Clickase”
  作者：Junfeng Chen、Ke Li、Sarah E. Bonson、Steven C. Zimmerman

  DOI：10.1021/jacs.0c06553

  日期：2020.8.12

  extracellular click chemistry to be performed. We describe two proof of principle applications that illustrate the utility of the bioorthogonal activity. First, the SCNP catalyst is able to screen for ligands that bind proteins, including PROTAC-like molecules. Second, the non-membrane permeable SCNP can efficiently catalyze the click reaction extracellularly, thereby enabling in situ anticancer drug

  合成聚合物支架可作为防止生物大分子粘附的守门人。在此，我们使用门控来开发含铜单链纳米颗粒 (SCNP) 催化剂作为人工“点击酶”，它选择性地作用于能够穿透聚合物壳的小分子。具有表面铵基团的类似点击酶对炔基化蛋白质和小分子底物进行高效的铜 (I) 催化的炔-叠氮化物环加成 (CuAAC) 反应，而具有聚乙二醇 (PEG) 基团的新型 SCNP 点击酶仅具有活性在小分子上。此外，新的 SCNP 可抵抗细胞摄取，从而可以进行细胞外点击化学。我们描述了两个原理应用证明，说明了生物正交活动的效用。第一的，SCNP 催化剂能够筛选结合蛋白质的配体，包括 PROTAC 样分子。其次，非膜渗透性SCNP可以有效地在细胞外催化点击反应，从而在不干扰细胞内功能的情况下实现原位抗癌药物合成和筛选。
• New Colchicine-Derived Triazoles and Their Influence on Cytotoxicity and Microtubule Morphology
  作者：Persefoni Thomopoulou、Julia Sachs、Nicole Teusch、Aruljothi Mariappan、Jay Gopalakrishnan、Hans-Günther Schmalz

  DOI：10.1021/acsmedchemlett.5b00418

  日期：2016.2.11

  A series of new colchicinoids with a variable triazole unit at C-7 was synthesized through Cu(I)-catalyzed 1,3-dipolar cycloaddition (click-chemistry) of a colchicine-derived azide with various alkynes and the cytotoxicity against THP-1 and Jurkat cancer cell lines was used for structural optimization. Three particularly active compounds (IC50 <= 5 nM) were additionally investigated with respect to their efficacy against relevant solid tumor cell lines (HeLa, A549, and SK MES 1). Besides distorting the microtubule morphology by tubulin depolymerization, one compound also exhibited a pronounced centrosome declustering effect in triple negative breast cancer cells (MDA-MB-231) and nonsmall cell lung cancer cells (H1975).
• Azoacetylenes for the Synthesis of Arylazotriazole Photoswitches
  作者：Patrick Pfaff、Felix Anderl、Moritz Fink、Moritz Balkenhohl、Erick M. Carreira

  DOI：10.1021/jacs.1c06014

  日期：2021.9.15

  TIPS-acetylene to aryldiazonium tetrafluoroborate salts gives a wide range of azoacetylenes, constituting an underexplored class of stable intermediates. In situ desilylation transiently leads to terminal arylazoacetylenes that undergo copper-catalyzed cycloadditions (CuAAC) with a diverse collection of organoazides. These include complex molecules derived from natural products or drugs, such as colchicine

  我们报告了一种针对新型芳基氮并三唑光开关及其光物理特性的模块化方法。锂化 TIPS-乙炔与芳基重氮四氟硼酸盐的加成得到范围广泛的偶氮乙炔，构成了一类尚未开发的稳定中间体。原位脱硅瞬时导致末端芳基偶氮乙炔发生铜催化环加成反应 (CuAAC)，并产生多种有机叠氮化物。这些包括源自天然产物或药物的复杂分子，例如秋水仙碱、紫杉醇、达菲和花生四烯酸。芳基氮并三唑显示近定量光异构化和长热Z-半条命。使用该方法，我们首次介绍了联乙炔平台的设计和合成。它允许实施连续和面向多样性的方法，将两种不同的偶联物连接到一个常见的光开关偶氮三唑中的独立可寻址乙炔。这在几种光开关偶联物的合成中得到了展示，具有作为 photoPROTAC 和生物素偶联物的潜在应用。
• A Convenient Entry to New C-7-Modified Colchicinoids through Azide Alkyne [3+2] Cycloaddition: Application of Ring-Contractive Rearrangements
  作者：Hans-Günther Schmalz、Norman Nicolaus、Jens Reball、Nikolay Sitnikov、Alexey Yu. Fedorov、Janna Velder、Andreas Termath

  DOI：10.3987/com-10-s(e)117

  日期：——

  Reliable procedures for the preparation of azides derived from colchicine (1), allocolchicine (3) and N-acetylcolchinol (4a) were developed. These azides were then employed in Cu-catalyzed Huisgen-Sharpless [3+2] cycloaddition ("click") reactions with alkynes under microwave irradiation. The method developed opens a convenient and efficient access to libraries of new C-7-modified colchicinoids (triazole derivatives). In addition, a plausible mechanistic rationale for the colchicine-allocolchicine rearrangement is suggested.