(2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(4'-chloro-6'-methylcyclohex-3'-ene-2'-one) | 1235-50-3

• 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,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(4'-chloro-6'-methylcyclohex-3'-ene-2'-one)
• 英文别名: 7,4'-Dichlor-4,6-dimethoxy-6'-methyl-3,2'-dioxo-spirocyclohexen>；7,4'-Dichlor-4,6-dimethoxy-6'-methyl-3,2'-dioxo-spiro[benzofuran-2(3H).1'-[3]cyclohexen]；(2S,5'R)-3',7-dichloro-4,6-dimethoxy-5'-methylspiro[1-benzofuran-2,6'-cyclohex-2-ene]-1',3-dione
• CAS: 1235-50-3
• 化学式: C₁₆H₁₄Cl₂O₅
• 分子量: 357.19
• InChiKey: DWFAJTZKBVTMQY-QZTNRIJFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 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：
  61.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  (2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(4'-chloro-6'-methylcyclohex-3'-ene-2'-one) 、 间甲氧基苯甲醇 在 1,8-二氮杂双环[5.4.0]十一碳-7-烯 作用下， 以 1,4-二氧六环 为溶剂， 反应 12.0h， 以32%的产率得到(2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(4'-(3-methoxybenzyl)oxy-6'-methylcyclohex-3'-ene-2'-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 、 溶剂黄146 、 lithium chloride 、 三氯氧磷 作用下， 以 1,4-二氧六环 为溶剂， 反应 0.5h， 生成 (2S,6'R)-(7-chloro-4,6-dimethoxy-benzofuran-3-one)-2-spiro-1'-(4'-chloro-6'-methylcyclohex-3'-ene-2'-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

文献信息

• Synthesis and Structure−Activity Relationship of Griseofulvin Analogues as Inhibitors of Centrosomal Clustering in Cancer Cells
  作者：Mads H. Rønnest、Blanka Rebacz、Lene Markworth、Anette H. Terp、Thomas O. Larsen、Alwin Krämer、Mads H. Clausen

  DOI：10.1021/jm801517j

  日期：2009.5.28

  Griseofulvin was identified as an inhibitor of centrosomal clustering in a recently developed assay. Centrosomal clustering is an important cellular event that enables bipolar mitosis for cancer cell lines harboring supernumerary centrosomes. We report herein the synthesis and SAR of 34 griseofulvin analogues as inhibitors of centrosomal clustering. The variations in the griseofulvin structure cover

  在最近开发的测定中，灰黄霉素被鉴定为中心体簇的抑制剂。中心体簇是重要的细胞事件，其使具有过多数量中心体的癌细胞系实现双极有丝分裂。我们在此报道了34个灰黄霉素的类似物的合成和SAR，其为中心体簇的抑制剂。灰黄霉素结构的变化覆盖五个位置，即4、5、2'，3'和4'位置。4和5位的修饰提供了非活性分子。烯醇醚必须位于2'位置，并且4'位置必须为sp 2杂交的。与灰黄霉素相比，活性最高的类似物是2'-苄氧基和2'-（4-甲基苄氧基）类似物，以及前者的肟，其活性增加了25倍。在这项工作中获得的结果与先前报道的皮肤真菌的生长抑制数据的比较显示了相同点和不同点。
• Synthesis and Antifungal Activity of Derivatives of the Natural Product Griseofulvin against Phytopathogenic Fungi
  作者：Yu-Bin Bai、Meng Zhang、Ding Li、Yu Zhao、Liang-Zhu Huang、Jin-Ming Gao

  DOI：10.1021/acs.jafc.2c09037

  日期：2023.4.26

  Furthermore, 12 showed remarkable activity against Cytospora sp. (IC50 = 5.85 ± 0.72 μg/mL). Additionally, in vivo antifungal activity against C. gloeosporioides, homology modeling, and docking analysis of 11, 12, and griseofulvin were conducted. All results indicated that 11 and 12 had potency as antifungal agents against C. gloeosporioides, and the modifications of the 2′ and 4′ positions of griseofulvin

  天然产物是发现新农药的重要来源。化学合成和结构修饰可产生杀虫剂。尽管在发现用于作物保护的杀菌剂方面进行了大量研究，但对开发新型抗真菌农用化学品的需求不断增加。本文以天然产物灰黄霉素为原料，通过去甲基化、氨解、甲基化、硝化、酰化、还原、氯化等反应，通过多样性导向合成，有效合成了39种多样化的灰黄霉素衍生物。其中，31个衍生物具有新颖性。所有结构均通过1 H NMR、13 C NMR 和高分辨率质谱 (HR-MS) 进行表征，并研究了其对五种植物病原真菌的抗真菌活性。化合物5h和5l分别对Botrytis cinerea（5h，IC 50 = 17.29 ± 0.64 μg/mL）和Alternaria solani（5l，IC 50 = 22.52 ± 0.79 μg/mL）具有出色的活性。化合物9对三种目标真菌表现出更有希望的活性，尤其是对胶孢炭疽菌(IC 50 = 7.24 ± 0.66