(+)-grandione | 247118-47-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (+)-grandione
• 英文别名: (1R,6S,11S,19R,24S,29S)-6,24-dihydroxy-10,10,28,28-tetramethyl-16,19-di(propan-2-yl)-2,18-dioxaheptacyclo[17.13.0.03,17.04,14.06,11.022,32.024,29]dotriaconta-3,14,16,22(32)-tetraene-20,21-dione
• CAS: 247118-47-4
• 化学式: C₄₀H₅₆O₆
• 分子量: 632.881
• InChiKey: NSFQHKIHYULDMH-BFPFMUMWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  7.7
• 重原子数：
  46
• 可旋转键数：
  2
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  93.1
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (+)-grandione 、 三甲基硅烷化重氮甲烷 以 甲醇 、 苯 为溶剂， 以90%的产率得到(1R,6S,11S,19R,20S,24S,29S)-6,24-dihydroxy-10,10,28,28-tetramethyl-16,19-di(propan-2-yl)spiro[2,18-dioxaheptacyclo[17.13.0.03,17.04,14.06,11.022,32.024,29]dotriaconta-3,14,16,22(32)-tetraene-20,2'-oxirane]-21-one
  参考文献：
  名称：

  Biomimetic synthesis of grandione from demethylsalvicanol via hetero-Diels–Alder type dimerization and structure revision of grandione

  摘要：

  Grandione, a unique isetexane diterpene dimer, was synthesized from demethylsalvicanol via the solid state hetero-Diels-Alder type dimerization reaction. By X-ray crystallography, grandione was determined to have the structure, in which the two isopropyl groups on the two monomer units are arranged syn. Grandione and some of its analogues showed a moderate cytotoxity on P388 murine leukemia cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.09.104
• 作为产物：
  描述：

  demethylsalvicanol 在 potassium dihydrogenphosphate 、 potassium nitrososulfonate 作用下， 以 丙酮 为溶剂， 反应 61.0h， 生成 (+)-grandione
  参考文献：
  名称：

  Biomimetic synthesis of grandione from demethylsalvicanol via hetero-Diels–Alder type dimerization and structure revision of grandione

  摘要：

  Grandione, a unique isetexane diterpene dimer, was synthesized from demethylsalvicanol via the solid state hetero-Diels-Alder type dimerization reaction. By X-ray crystallography, grandione was determined to have the structure, in which the two isopropyl groups on the two monomer units are arranged syn. Grandione and some of its analogues showed a moderate cytotoxity on P388 murine leukemia cells. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tetlet.2005.09.104

文献信息

• Efficient Synthesis of Icetexane Diterpenes and Apoptosis Inducing Effect by Upregulating BiP-ATF4-CHOP Axis in Colorectal Cells
  作者：Wei Cao、Tingting Liu、Shuting Yang、Moude Liu、Zhenghong Pan、Yingjun Zhou、Xu Deng

  DOI：10.1021/acs.jnatprod.1c00310

  日期：2021.7.23

  We herein present an efficient and robust synthetic strategy toward 12 icetexane diterpenes and their derivatives, which features a PPh3/DIAD-mediated rearrangement of the reduced carnosic acid derivative (2) to give (−)-barbatusol (3) in a regioselective and scalable way. MTT assay led to the identification of (+)-grandione (11) and (−)-demethylsalvicanol o-quinone derivative (9) as highly cytotoxic

  本文我们提出朝向12个icetexane二萜及它们的衍生物，其特点是PPH的高效且健壮的合成策略3的缩小鼠尾草酸衍生物/ DIAD介导的重排（2），得到（ - ） - barbatusol（3中区域选择性）和可扩展的方式。MTT 测定导致将 (+)-格兰二酮( 11 ) 和 (-)-去甲基丹参醇邻苯醌衍生物 ( 9 )鉴定为对 HCT-116、COLO-205 和 Caco-2 细胞具有高度细胞毒性的药物。有趣的是，(+)-grandione ( 11) 以剂量依赖性方式诱导 HCT-116 细胞凋亡，这可能归因于 BiP-ATF4-CHOP 轴的上调和 BiP-ATF4 相互作用的促进，从而导致内质网 (ER) 应激。这项工作不仅为获得icetexane二萜铺平了有效且可扩展的途径，而且还为具有独特作用模式的抗结直肠药物的开发提供了新的线索。
• Total Synthesis of (−)-Barbatusol, (+)-Demethylsalvicanol, (−)-Brussonol, and (+)-Grandione
  作者：George Majetich、Ge Zou

  DOI：10.1021/ol701800d

  日期：2008.1.1

  The icetexane-based diterpenes (-)-barbatusol, (+)-demethylsalvicanol, and (-)-brussonol were synthesized. Synthetic demethylsalvicanol was dimerized to produce (+)-grandione using aqueous Diels-Alder conditions.