45,46-dehydrobromo-phorboxazole A | 340703-24-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 唑类
• 英文名称: 45,46-dehydrobromo-phorboxazole A
• 英文别名: 45,46-dehydrobromophorboxazole；(1R,6E,9R,11R,12R,13S,16Z,19S,23R,25S,27R,31S)-27-hydroxy-11-[(E)-1-[2-[[(2S,4R,6R)-2-hydroxy-6-[(1R,2E,4E,6R)-1-hydroxy-6-methoxy-3-methylnona-2,4-dien-8-ynyl]-4-methoxyoxan-2-yl]methyl]-1,3-oxazol-4-yl]prop-1-en-2-yl]-12,31-dimethyl-21-methylidene-4,10,14,29,30-pentaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one
• CAS: 340703-24-4
• 化学式: C₅₃H₇₀N₂O₁₃
• 分子量: 943.144
• InChiKey: DFCPSFLWZFKTME-ZFLJMKJUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  68
• 可旋转键数：
  11
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.6
• 拓扑面积：
  194
• 氢给体数：
  3
• 氢受体数：
  15

反应信息

• 作为反应物：
  描述：

  、 45,46-dehydrobromo-phorboxazole A 在 bis-triphenylphosphine-palladium(II) chloride 、 copper(l) iodide 、 三乙胺 作用下， 以 四氢呋喃 为溶剂， 反应 0.08h， 以82%的产率得到(1R,6E,9R,11R,12R,13S,16Z,19S,23R,25S,27R,31S)-11-[(E)-1-[2-[[(2S,4R,6R)-6-[(1R,2E,4E,6R,10E)-12-[2-[3-[7-(diethylamino)-2-oxochromen-4-yl]propoxy]ethoxy]-1-hydroxy-6-methoxy-3-methyldodeca-2,4,10-trien-8-ynyl]-2-hydroxy-4-methoxyoxan-2-yl]methyl]-1,3-oxazol-4-yl]prop-1-en-2-yl]-27-hydroxy-12,31-dimethyl-21-methylidene-4,10,14,29,30-pentaoxa-32-azapentacyclo[23.3.1.12,5.19,13.119,23]dotriaconta-2,5(32),6,16-tetraen-15-one
  参考文献：
  名称：

  Phorboxazole Analogues Induce Association of cdk4 with Extranuclear Cytokeratin Intermediate Filaments

  摘要：

  The cellular localization profile and molecular association of the phorboxazoles were examined with a streamlined target elucidation system using synthetic fluorescent probes. Cellular image analyses identified the binding of phorboxazole analogues to cytosolic components. Proteomic analysis directed at fluorescently labeled cytosolic fractions indicated that the primary targets observed microscopically were cytokeratins, as verified by determination of low nanomolar binding to cloned and expressed proteins. Phorboxazole probes localized the essential cell cycle promoter cdk4 upon cytokeratin networks.

  DOI：

  10.1021/ja057087e
• 作为产物：
  描述：

  2-[(2S,4R,6R)-2,4-Dimethoxy-6-((2E,4E)-(1R,6R)-6-methoxy-3-methyl-1-triisopropylsilanyloxy-9-trimethylsilanyl-nona-2,4-dien-8-ynyl)-tetrahydro-pyran-2-ylmethyl]-4-trimethylstannanyl-oxazole 在 tris(dibenzylideneacetone)dipalladium(0) chloroform complex 三苯胂 、 四丁基氟化铵 、 N,N-二异丙基乙胺 、 Tetrabutylammoniumsalz der Diphenylphosphinsaeure 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 53.0h， 生成 45,46-dehydrobromo-phorboxazole A
  参考文献：
  名称：

  （+）-苯甲唑A的合成研究。一系列高度细胞毒性的C（45-46）类似物的鉴定。

  摘要：

  [结构：见正文]已经实现了六种邻苯二唑A类似物（1-6）的有效，可扩展的总合成和生物学评估。重要的是，饱和的C（45-46），C（45-46）-烯基和C（45-46）-E-氯代烯基同类物（分别为4、5和6）显示出低的纳摩尔肿瘤细胞生长在多种人类癌细胞系中，其抑制活性（GI50）类似于或在某些细胞系中均比邻苯二恶唑更高。

  DOI：

  10.1021/ol051585a

文献信息

• Total synthesis of a biotinylated derivative of phorboxazole A via sonogashira coupling
  作者：T.Matthew Hansen、Mary M. Engler、Craig J. Forsyth

  DOI：10.1016/s0960-894x(03)00355-x

  日期：2003.7

  The C46 terminus of phorboxazole A has been modified to incorporate a biotin-terminated linker via direct palladium-mediated Sonogashira reaction conditions. Synthetic 45,46-dehydrobromophorboxazole A was joined with a tris-(polyethyleneglycol)vinyl iodide-biotin ester using catalytic PdCl(2)(PPh(3))(2), CuI, and Et(3)N in THF. This process demonstrates the utility of mild carbon-carbon bond formation

  佛波唑A的C46末端经过修饰，可以通过直接的钯介导的Sonogashira反应条件掺入生物素封端的接头。使用催化的PdCl（2）（PPh（3））（2），CuI和Et（3）N在THF中将合成的45,46-脱氢溴代邻苯二甲唑A与三（聚乙二醇）乙烯基碘化物-生物素酯连接。该方法证明了在phorboxazoles的体系结构中温和的碳-碳键形成的效用，并提供了潜在的亲和探针。
• Phorboxazole compounds and methods of their preparation
  申请人：The Trustees of the University of Pennsylvania

  公开号：US07485631B2

  公开（公告）日：2009-02-03

  Novel macrolactone compounds, their methods of preparation, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the macrolactone compounds may be useful, inter alia, for treating various cancers, inducing apoptosis in malignant cells, or inhibiting cancer cell division.

  新型大环内酯化合物，其制备方法，含有这些化合物的药物组合物，以及这些药物的药用方法被披露。在某些实施例中，这些大环内酯化合物可能有助于治疗各种癌症，诱导恶性细胞凋亡，或抑制癌细胞分裂。
• Phorboxazole Compounds and Methods of Their Preparation
  申请人：Razler Thomas M.

  公开号：US20090163563A1

  公开（公告）日：2009-06-25

  Novel macrolactone compounds, their methods of preparation, pharmaceutical compositions containing these compounds, and methods for their pharmaceutical use are disclosed. In certain embodiments, the macrolactone compounds may be useful, inter alia, for treating various cancers, inducing apoptosis in malignant cells, or inhibiting cancer cell division.
• US7485631B2
  申请人：——

  公开号：US7485631B2

  公开（公告）日：2009-02-03
• Phorboxazole Analogues Induce Association of cdk4 with Extranuclear Cytokeratin Intermediate Filaments
  作者：Craig J. Forsyth、Lu Ying、Jiehao Chen、James J. La Clair

  DOI：10.1021/ja057087e

  日期：2006.3.1

  The cellular localization profile and molecular association of the phorboxazoles were examined with a streamlined target elucidation system using synthetic fluorescent probes. Cellular image analyses identified the binding of phorboxazole analogues to cytosolic components. Proteomic analysis directed at fluorescently labeled cytosolic fractions indicated that the primary targets observed microscopically were cytokeratins, as verified by determination of low nanomolar binding to cloned and expressed proteins. Phorboxazole probes localized the essential cell cycle promoter cdk4 upon cytokeratin networks.