(2R,3R,4R)-2-(4-hydroxyphenyl)-7-hydroxy-4-(2,4,6-trihydroxy-3-(dodecanoyl)phenyl)chromane

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: (2R,3R,4R)-2-(4-hydroxyphenyl)-7-hydroxy-4-(2,4,6-trihydroxy-3-(dodecanoyl)phenyl)chromane
• 英文别名: (+)-myristinin A；myristinin A；1-[2,4,6-trihydroxy-3-[(2S,4R)-7-hydroxy-2-(4-hydroxyphenyl)-3,4-dihydro-2H-chromen-4-yl]phenyl]dodecan-1-one
• 化学式: C₃₃H₄₀O₇
• 分子量: 548.676
• InChiKey: JGXZVDAPLSTBGZ-IRPSRAIASA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.9
• 重原子数：
  40
• 可旋转键数：
  13
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  127
• 氢给体数：
  5
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  间苯三酚 在 4-二甲氨基吡啶 、 palladium dihydroxide 、 三氟甲磺酸三甲基硅酯 、 phenyl trichloroformate 、 三氟化硼乙醚 、 potassium carbonate 作用下， 以 四氢呋喃 、 甲醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 65.5h， 生成 (2R,3R,4R)-2-(4-hydroxyphenyl)-7-hydroxy-4-(2,4,6-trihydroxy-3-(dodecanoyl)phenyl)chromane
  参考文献：
  名称：

  (+)-Myristinin A, a Naturally Occurring DNA Polymerase β Inhibitor and Potent DNA-Damaging Agent

  摘要：

  The first stereoselective total synthesis of the naturally occurring flavan myristinin A has been accomplished, as well as its biochemical evaluation. This synthesis verified the structural assignment and allowed for the determination of the absolute stereochemistry. Myristinin A exhibits biochemical activity both as a potent DNA-damaging agent and DNA polymerase beta inhibitor. Relaxation of supercoiled plasmid DNA was observed at picomolar concentrations, in addition to inhibition of polymerase beta at low micromolar concentrations.

  DOI：

  10.1021/ja042727j

文献信息

• Total synthesis of myristinins A–F and 3′-hydroxy-5,7-dimethoxy-4-<i>O</i>-2′-cycloflavan by iterative generation of <i>o</i>-quinone methides
  作者：Santosh J. Gharpure、S. Jegadeesan、Dharmendra S. Vishwakarma

  DOI：10.1039/d2nj00244b

  日期：——

  An iterative generation of o-quinone methides (o-QMs) and [4+2] cycloaddition followed by inter/intra-molecular Michael addition in a cascade sequence gave expedient access to total synthesis of myristinins A–F and 3′-hydroxy-5,7-dimethoxy-4-O-2′-cycloflavan and their analogues, respectively. This cascade sequence cyclisation successfully provided the shortest route to the gram-scale synthesis of the

  邻醌甲基化物 ( o -QMs) 和 [4+2] 环加成，然后是级联序列中分子间/分子内 Michael 加成的迭代生成，方便了肉豆蔻素 A-F 和 3'-羟基-的全合成。分别为 5,7-dimethoxy-4- O -2'-cycloflavan 及其类似物。这种级联序列环化成功地为肉豆蔻素家族的克级合成提供了最短途径，包括首次全合成肉豆蔻素 D-F 和 3'-hydroxy-5,7-dimethoxy-4- O -2'-cycloflavan .
• Stereoselective Synthesis of the Atropisomers of Myristinin B/C
  作者：David J. Maloney、Shengxi Chen、Sidney M. Hecht

  DOI：10.1021/ol060511b

  日期：2006.4.1

  [reaction: see text] The first stereoselective synthesis of a potent DNA damaging agent, (-)-myristinin B/C, has been accomplished. This efficient synthesis allowed for unambiguous confirmation of the structure and absolute stereochemistry of the atropisomeric natural product. The antipode, (+)-myristinin B/C, was also synthesized, providing ample material for biological evaluation of both enantiomers

  [反应：见正文]已经完成了一种有效的DNA破坏剂（-）-myristinin B / C的首次立体选择性合成。这种有效的合成可以明确确认阻转异构天然产物的结构和绝对立体化学。还合成了对映体（+）-肉豆蔻素B / C，为两种对映体的生物学评估提供了充足的材料。
• INHIBITING DNA POLYMERASE BETA TO ENHANCE EFFICACY OF ANTICANCER AGENTS
  申请人：Sobol Robert W.

  公开号：US20090081119A1

  公开（公告）日：2009-03-26

  The invention provides anticancer methods. In one embodiment, the inventive method involves the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an inhibitor of DNA polymerase beta. In another embodiment, the invention provides anticancer methods involving the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an siRNA or shRNA in an amount sufficient to attenuate base excision repair within the cell. Another aspect of the invention relates to pharmaceutical compositions comprising an siRNA or shRNA that attenuates base excision repair.
• [EN] INHIBITING DNA POLYMERASE BETA TO ENHANCE EFFICACY OF ANTICANCER AGENTS<br/>[FR] INHIBITION D'ADN POLYMERASE BETA POUR AMELIORER L'EFFICACITE D'AGENTS ANTICANCEREUX
  申请人：UNIV PITTSBURGH

  公开号：WO2007001684A2

  公开（公告）日：2007-01-04

  (EN) The invention provides anticancer methods. In one embodiment, the inventive method involves the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an inhibitor of DNA polymerase beta. In another embodiment, the invention provides anticancer methods involving the co-administration to cancerous cells of (a) a chemotherapeutic agent, radiation, or a combination of a chemotherapeutic agent and radiation and (b) an siRNA or shRNA in an amount sufficient to attenuate base excision repair within the cell. Another aspect of the invention relates to pharmaceutical compositions comprising an siRNA or shRNA that attenuates base excision repair.(FR) La présente invention a trait à des procédés anticancéreux. Dans un mode de réalisation, le procédé de l'invention comprend l'administration conjointe à des cellules cancéreuses (a) d'un agent chimiothérapeutique, d'une radiothérapie, ou d'une combinaison d'agent chimiothérapeutique et de radiothérapie et (b) d'un inhibiteur de l'ADN polymérase bêta. Dans un autre mode de réalisation, l'invention a trait à des procédés anticancéreux comprenant l'administration conjointe aux cellules cancéreuses (a) d'un agent chimiothérapeutique, d'une radiothérapie, ou d'une combinaison d'agent chimiothérapeutique et de radiothérapie et (b) d'un ARNsi ou d'un ARNsh en une quantité suffisante pour atténuer la réparation par excision de base au sein de la cellule. Dans un autre aspect, l'invention a trait à des compositions pharmaceutiques comportant un ARNsi ou ARNsh qui atténue la réparation par excision de base.
• (+)-Myristinin A, a Naturally Occurring DNA Polymerase β Inhibitor and Potent DNA-Damaging Agent
  作者：David J. Maloney、Jing-Zhen Deng、Shelley R. Starck、Zhijie Gao、Sidney M. Hecht

  DOI：10.1021/ja042727j

  日期：2005.3.1

  The first stereoselective total synthesis of the naturally occurring flavan myristinin A has been accomplished, as well as its biochemical evaluation. This synthesis verified the structural assignment and allowed for the determination of the absolute stereochemistry. Myristinin A exhibits biochemical activity both as a potent DNA-damaging agent and DNA polymerase beta inhibitor. Relaxation of supercoiled plasmid DNA was observed at picomolar concentrations, in addition to inhibition of polymerase beta at low micromolar concentrations.