(2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-6a,10b-dimethyl-4,10-dioxododecahydro-1H-benzo[f ]isochromene-7-carboxylate

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 萘并吡喃类
• 英文名称: (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-6a,10b-dimethyl-4,10-dioxododecahydro-1H-benzo[f ]isochromene-7-carboxylate
• 英文别名: methyl (2S,4aR,6aR,7R,9S,10aS,10bR)-9-acetyloxy-2-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-6a,10b-dimethyl-4,10-dioxo-2,4a,5,6,7,8,9,10a-octahydro-1H-benzo[f]isochromene-7-carboxylate
• 化学式: C₂₆H₃₀O₉
• 分子量: 486.519
• InChiKey: BGFZJVOSAUXBPR-KQDZFTLOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.1
• 重原子数：
  35
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  130
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  丹酚 A 在 N-甲基吗啉 、 三乙基硅烷 、 ruthenium trichloride 、 sodium periodate 、 ammonium cerium (IV) nitrate 、 2-氯-4,6-二甲氧基-1,3,5-三嗪 、 三氟化硼乙醚 、 bis(dibenzylideneacetone)-palladium⁽⁰⁾ 、 (R)-2-甲基-CBS-恶唑硼烷 、 亚磷酸三乙酯 作用下， 以 四氢呋喃 、 四氯化碳 、 二氯甲烷 、 水 、 甲苯 、 乙腈 为溶剂， 反应 0.08h， 生成 (2S,4aR,6aR,7R,9S,10aS,10bR)-methyl 9-acetoxy-2-[(3,6-dioxocyclohexa-1,4-dien-1-yl)methyl]-6a,10b-dimethyl-4,10-dioxododecahydro-1H-benzo[f ]isochromene-7-carboxylate
  参考文献：
  名称：

  Studies toward the Development of Antiproliferative Neoclerodanes from Salvinorin A

  摘要：

  The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoderodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the x-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.

  DOI：

  10.1021/np5002048

文献信息

• Studies toward the Development of Antiproliferative Neoclerodanes from Salvinorin A
  作者：Tamara Vasiljevik、Chad E. Groer、Kurt Lehner、Hernan Navarro、Thomas E. Prisinzano

  DOI：10.1021/np5002048

  日期：2014.8.22

  The success rate for central nervous system (CNS) drug candidates in the clinic is relatively low compared to the industry average across other therapeutic areas. Penetration through the blood-brain barrier (BBB) to reach the therapeutic target is a major obstacle in development. The rapid CNS penetration of salvinorin A has suggested that the neoderodane nucleus offers an excellent scaffold for developing antiproliferative compounds that enter the CNS. The Liebeskind-Srogl reaction was used as the main carbon-carbon bond-forming step toward the synthesis of quinone-containing salvinorin A analogues. Quinone-containing salvinorin A analogues were shown to have antiproliferative activity against the MCF7 breast cancer cell line, but show no significant activity at the x-opioid receptors. In an in vitro model of BBB penetration, quinone-containing salvinorin A analogues were shown to passively diffuse across the cell monolayer. The analogues, however, are substrates of P-glycoprotein, and thus further modification of the molecules is needed to reduce the affinity for the efflux transporter.