10-hydroxy-2,2-dimethyl-3a-(3-methylbut-2-en-1-yl)-1,2-dihydro-1,5-methanofuro[2,3-d]xanthene-4,7(3aH,5H)-dione | 1301160-10-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并吡喃
• 英文名称: 10-hydroxy-2,2-dimethyl-3a-(3-methylbut-2-en-1-yl)-1,2-dihydro-1,5-methanofuro[2,3-d]xanthene-4,7(3aH,5H)-dione
• 英文别名: MAD44；6-Hydroxy-17,17-dimethyl-15-(3-methylbut-2-enyl)-3,16-dioxapentacyclo[11.4.1.02,11.02,15.04,9]octadeca-4(9),5,7,11-tetraene-10,14-dione
• CAS: 1301160-10-0
• 化学式: C₂₃H₂₄O₅
• 分子量: 380.441
• InChiKey: VLADFNOTLYCWMW-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  28
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  72.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  10-hydroxy-2,2-dimethyl-3a-(3-methylbut-2-en-1-yl)-1,2-dihydro-1,5-methanofuro[2,3-d]xanthene-4,7(3aH,5H)-dione 、 对甲苯磺酸三缩乙二醇单甲醚酯 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 以86%的产率得到CR140
  参考文献：
  名称：

  Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer

  摘要：

  Inflammatory breast cancer (IBC) is a highly metastatic, lethal form of breast cancer that lacks targeted therapeutic strategies. Inspired by the promising cytotoxicity of gambogic acid and related caged xanthones in spheroids(MARY-X), an in vitro preclinical IBC model, we constructed a library of synthetic analogs and performed structure-activity relationship studies. The studies revealed that functionalizing the A-ring of the caged xanthone framework can significantly affect potency. Specifically, introduction of hydroxyl or fluorine groups at discrete positions of the A-ring leads to enhanced cytotoxicity at sub-micromolar concentrations. These compounds induce complete dissolution of spheroids(MARY-X) with subsequent apoptosis of both the peripherally- and centrally-located cells, proliferative and quiescent-prone (e.g. hypoxic), respectively. These results highlight the structural flexibility and pharmacological potential of the caged xanthone motif for the design of IBC-targeting therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2019.02.047
• 作为产物：
  描述：

  9-(methoxymethoxy)-2,2-diphenyl-6H-[1,3]dioxolo[4,5-c]xanthen-6-one 在 四(三苯基膦)钯 、 palladium 10% on activated carbon 、 氢气 、 碳酸氢钠 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 44.0h， 生成 10-hydroxy-2,2-dimethyl-3a-(3-methylbut-2-en-1-yl)-1,2-dihydro-1,5-methanofuro[2,3-d]xanthene-4,7(3aH,5H)-dione
  参考文献：
  名称：

  A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones

  摘要：

  被笼罩的伽马林黄酮(CGX)家族的天然产物具有独特的化学结构、强大的生物活性和良好的药理特征。我们开发了一种Claisen/Diels–Alder反应级联反应，并结合Pd(0)催化的逆普瑞尼基反应，快速高效地获得了以cluvenone结构为代表的CGX药效基团。为进一步探索该药效基团，我们合成了多种cluvenone的A环氧化类衍生物，并评估了它们在生长抑制、线粒体碎片化、诱导线粒体依赖性细胞死亡和Hsp90底物抑制等方面的生物活性。我们发现，在A环不同位置引入氧功能团显著影响了Claisen/Diels–Alder反应的位点选择性以及这些化合物的生物活性，原因在于远程电子效应。

  DOI：

  10.1039/c3ob40395e

文献信息

• GARCINIA DERIVATIVE, ITS PREPARING METHOD AND MEDICINAL USE
  申请人：You Qidong

  公开号：US20120059050A1

  公开（公告）日：2012-03-08

  The present invention relates to a field of pharmaceutical chemistry, more specifically, the present invention relates to a garcinia derivative Formula (I), its preparing method, and medicinal use. Wherein the definitions of R 1 and R 2 are disclosed in the specification of the present invention, and the derivative of the present invention is a structurally simplified analogue of the gambogic acid compound; wherein the gambogic acid compound possesses anti-cancer characteristics, and could be used for preparation of anti-tumor drugs.

  本发明涉及药物化学领域，更具体地说，本发明涉及一种藤黄衍生物配方（I），其制备方法和药用。其中，R1和R2的定义在本发明的说明书中披露，本发明的衍生物是甘黄酸化合物的结构简化类似物；甘黄酸化合物具有抗癌特性，可用于制备抗肿瘤药物。
• US8501803B2
  申请人：——

  公开号：US8501803B2

  公开（公告）日：2013-08-06
• Synthesis, structure-activity relationship and in vitro pharmacodynamics of A-ring modified caged xanthones in a preclinical model of inflammatory breast cancer
  作者：Oraphin Chantarasriwong、Andrew T. Milcarek、Theodore Habarth Morales、Aspen L. Settle、Celso O. Rezende、Bashayer D. Althufairi、Maria A. Theodoraki、Mary L. Alpaugh、Emmanuel A. Theodorakis

  DOI：10.1016/j.ejmech.2019.02.047

  日期：2019.4

  Inflammatory breast cancer (IBC) is a highly metastatic, lethal form of breast cancer that lacks targeted therapeutic strategies. Inspired by the promising cytotoxicity of gambogic acid and related caged xanthones in spheroids(MARY-X), an in vitro preclinical IBC model, we constructed a library of synthetic analogs and performed structure-activity relationship studies. The studies revealed that functionalizing the A-ring of the caged xanthone framework can significantly affect potency. Specifically, introduction of hydroxyl or fluorine groups at discrete positions of the A-ring leads to enhanced cytotoxicity at sub-micromolar concentrations. These compounds induce complete dissolution of spheroids(MARY-X) with subsequent apoptosis of both the peripherally- and centrally-located cells, proliferative and quiescent-prone (e.g. hypoxic), respectively. These results highlight the structural flexibility and pharmacological potential of the caged xanthone motif for the design of IBC-targeting therapeutics. (C) 2019 Elsevier Masson SAS. All rights reserved.
• A-ring oxygenation modulates the chemistry and bioactivity of caged Garcinia xanthones
  作者：Kristyna M. Elbel、Gianni Guizzunti、Maria A. Theodoraki、Jing Xu、Ayse Batova、Marianna Dakanali、Emmanuel A. Theodorakis

  DOI：10.1039/c3ob40395e

  日期：——

  Natural products of the caged Garcinia xanthones (CGX) family are characterized by a unique chemical structure, potent bioactivities and promising pharmacological profiles. We have developed a Claisen/Diels–Alder reaction cascade that, in combination with a Pd(0)-catalyzed reverse prenylation, provides rapid and efficient access to the CGX pharmacophore, represented by the structure of cluvenone. To further explore this pharmacophore, we have synthesized various A-ring oxygenated analogues of cluvenone and have evaluated their bioactivities in terms of growth inhibition, mitochondrial fragmentation, induction of mitochondrial-dependent cell death and Hsp90 client inhibition. We found that installation of an oxygen functionality at various positions of the A-ring influences significantly both the site-selectivity of the Claisen/Diels–Alder reaction and the bioactivity of these compounds, due to remote electronic effects.

  被笼罩的伽马林黄酮(CGX)家族的天然产物具有独特的化学结构、强大的生物活性和良好的药理特征。我们开发了一种Claisen/Diels–Alder反应级联反应，并结合Pd(0)催化的逆普瑞尼基反应，快速高效地获得了以cluvenone结构为代表的CGX药效基团。为进一步探索该药效基团，我们合成了多种cluvenone的A环氧化类衍生物，并评估了它们在生长抑制、线粒体碎片化、诱导线粒体依赖性细胞死亡和Hsp90底物抑制等方面的生物活性。我们发现，在A环不同位置引入氧功能团显著影响了Claisen/Diels–Alder反应的位点选择性以及这些化合物的生物活性，原因在于远程电子效应。