(2S,5'R)-7-chloro-6-hydroxy-3',4-dimethoxy-5'-methylspiro[1-benzofuran-2,6'-cyclohex-2-ene]-1',3-dione | 1354716-51-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (2S,5'R)-7-chloro-6-hydroxy-3',4-dimethoxy-5'-methylspiro[1-benzofuran-2,6'-cyclohex-2-ene]-1',3-dione
• CAS: 1354716-51-0
• 化学式: C₁₆H₁₅ClO₆
• 分子量: 338.745
• InChiKey: BOBFBEVZUHZXCZ-QZTNRIJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  23
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (2S,5'R)-7-chloro-6-hydroxy-3',4-dimethoxy-5'-methylspiro[1-benzofuran-2,6'-cyclohex-2-ene]-1',3-dione 在 camphor-10-sulfonic acid 、 silver(l) oxide 作用下， 以 1,4-二氧六环 为溶剂， 反应 72.0h， 生成 (2S,6'R)-(7-chloro-6-ethoxy-4-methoxy-benzofuran-3-one)-2-spiro-1'-(2'-methoxy-6'-methylcyclohex-2'-ene-4'-one)
  参考文献：
  名称：

  Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells

  摘要：

  Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A comparison of the antifungal the anticancer SAR revealed distinct differences, as the majority of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.

  DOI：

  10.1021/jm200835c
• 作为产物：
  描述：

  灰黄霉素 在 硫酸 、 水 、 溶剂黄146 、 sodium hydroxide 作用下， 生成 (2S,5'R)-7-chloro-6-hydroxy-3',4-dimethoxy-5'-methylspiro[1-benzofuran-2,6'-cyclohex-2-ene]-1',3-dione
  参考文献：
  名称：

  改善灰黄霉素类似物的溶解度和代谢稳定性的策略

  摘要：

  我们报告了对天然产物灰黄霉素的两种类型的修饰，以作为提高溶解度和代谢稳定性的策略：在代谢热点将芳基甲基醚转化为芳基二氟甲基醚，以及将C环酮转化为极性肟。描述了类似物的合成及其在两种癌细胞系中的溶解度，体外代谢半衰期和抗增殖作用。我们得出的结论是，总的来说，极性肟的形成是改善类似物性能的最有希望的策略。

  DOI：

  10.1016/j.ejmech.2016.03.071

文献信息

• Synthesis and single crystal X-ray analysis of two griseofulvin metabolites
  作者：Mads H. Rønnest、Pernille Harris、Charlotte H. Gotfredsen、Thomas O. Larsen、Mads H. Clausen

  DOI：10.1016/j.tetlet.2010.08.095

  日期：2010.11

  The two phenols, 6-O-desmethyl griseofulvin and 4-O-desmethyl griseofulvin are metabolites of the antifungal drug griseofulvin. Herein, we present an improved synthesis of the 6-phenol derivative, and an unequivocal proof of both structures by single-crystal X-ray analysis.

  两种酚6- O-去甲基灰黄霉素和4- O-去甲基灰黄霉素是抗真菌药物灰黄霉素的代谢产物。在这里，我们提出了改进的6-酚衍生物的合成，并通过单晶X射线分析清楚地证明了这两种结构。
• Disparate SAR Data of Griseofulvin Analogues for the Dermatophytes Trichophyton mentagrophytes, T. rubrum, and MDA-MB-231 Cancer Cells
  作者：Mads H. Rønnest、Marc S. Raab、Simon Anderhub、Sven Boesen、Alwin Krämer、Thomas O. Larsen、Mads H. Clausen

  DOI：10.1021/jm200835c

  日期：2012.1.26

  Griseofulvin and 53 analogues of this compound have been tested against the pathogenic dermatophytes Trichophyton rubrum and Trichophyton mentagrophytes as well as against the breast cancer cell line MDA-MB-231. The modifications to griseofulvin include the 4, 5, 6, 2', 3', and 4' positions. The SAR of the griseofulvin analogues toward the two fungi followed the same trend with the majority being less active than griseofulvin and none had more than twice the potency of the parent compound. A comparison of the antifungal the anticancer SAR revealed distinct differences, as the majority of analogues showed increased activity against the cancer cell line MDA-MB-231, highlighted by 2'-benzyloxy-2'-demethoxy-griseofulvin, which showed low activity against both fungi but was among the most potent compounds against MDA-MB-231 cancer cells. Tubulin has been proposed as the target of griseofulvin in both fungal and mammalian cells, but the differences revealed by this SAR study strongly suggest that the mode-of-action of the compound class toward fungi and mammalian cancer cells is different.
• Strategies for improving the solubility and metabolic stability of griseofulvin analogues
  作者：A.B. Petersen、G. Konotop、N.H.M. Hanafiah、P. Hammershøj、M.S. Raab、A. Krämer、M.H. Clausen

  DOI：10.1016/j.ejmech.2016.03.071

  日期：2016.6

  We report two types of modifications to the natural product griseofulvin as strategies to improve solubility and metabolic stability: the conversion of aryl methyl ethers into aryl difluoromethyl ethers at metabolic hotspots and the conversion of the C-ring ketone into polar oximes. The syntheses of the analogues are described together with their solubility, metabolic half-life in vitro and antiproliferative

  我们报告了对天然产物灰黄霉素的两种类型的修饰，以作为提高溶解度和代谢稳定性的策略：在代谢热点将芳基甲基醚转化为芳基二氟甲基醚，以及将C环酮转化为极性肟。描述了类似物的合成及其在两种癌细胞系中的溶解度，体外代谢半衰期和抗增殖作用。我们得出的结论是，总的来说，极性肟的形成是改善类似物性能的最有希望的策略。