(5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate

• 分子结构分类: 有机化合物 - 木脂素、新木脂素和相关化合物 - 芳基四氢萘木脂素
• 英文名称: (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate
• 英文别名: monomethyl 3-formyl-(1R,2R)-1-(3,4,5-trimethoxyphenyl)-6,7-methylenedioxy-1,2-dihydronaphthalene-2-carboxylate ester；Methyl (7R,8R)-6-formyl-8-(3,4,5-trimethoxyphenyl)-7,8-dihydrobenzo[f][1,3]benzodioxole-7-carboxylate
• 化学式: C₂₃H₂₂O₈
• 分子量: 426.423
• InChiKey: GITXTLWTFJXXKT-RTWAWAEBSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.3
• 拓扑面积：
  89.5
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate 在 sodium tetrahydroborate 作用下， 以 甲醇 为溶剂， 反应 0.5h， 以90%的产率得到monomethyl 3-(hydroxymethyl)-(1R,2R)-1-(3,4,5-trimethoxyphenyl)-6,7-methylenedioxy-1,2-dihydronaphthalene-2-carboxylate ester
  参考文献：
  名称：

  通过轴向手性3,4-双亚苄基琥珀酸酰胺酯的光环化，正式合成（-）-鬼臼毒素–流动光化学方法†

  摘要：

  我们已经开发了与鬼臼毒素及其衍生物有关的立体选择性合成环木脂体的策略。合成的关键步骤是手性阻转异构体1,2-双亚苄基琥珀酸酯酰胺酯的光环化，该酯可由合适的芳族醛，琥珀酸二乙酯和L-脯氨醇制备。当在自制的连续流光化学反应器中进行辐照时，发现光环化更有效。流入辐射还使我们能够以克数进行反应。用Schwartz试剂还原性裂解除去手性助剂，得到具有细胞毒性的1 R，2 R-顺式-鬼臼乙醛，可以轻松地将其还原为相应的醇，从而完成（-）-鬼臼毒素的正式合成。

  DOI：

  10.1039/c5ob01844g
• 作为产物：
  描述：

  (5R,6R,7R)-methyl 7-(hydroxymethyl)-8-oxo-5-(3,4,5-trimethoxyphenyl)-5,6,7,8-tetrahydronaphtho[2,3-d][1,3]dioxole-6-carboxylate 在 sodium tetrahydroborate 、 草酰氯 、 二甲基亚砜 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 3.5h， 生成 (5R,6R)-methyl 7-formyl-5-(3,4,5-trimethoxyphenyl)-5,6-dihydronaphtho[2,3-d][1,3]dioxole-6-carboxylate
  参考文献：
  名称：

  Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors

  摘要：

  A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 μM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.

  DOI：

  10.1016/j.bmc.2014.07.031

文献信息

• Synthesis and biological evaluation of podophyllotoxin congeners as tubulin polymerization inhibitors
  作者：Ahmed Kamal、T. Srinivasa Reddy、Sowjanya Polepalli、Nekkanti Shalini、V. Ganga Reddy、A.V. Subba Rao、Nishant Jain、Nagula Shankaraiah

  DOI：10.1016/j.bmc.2014.07.031

  日期：2014.10

  A series of new podophyllotoxin derivatives containing structural modifications at C-7, C-8, and C-9 were synthesized and evaluated for their cytotoxic activity against three human cancer cell lines. All the synthesized compounds showed significant growth inhibition with GI50 values in micromolar levels while some of the compounds were several times more potent against MCF-7 and HeLa cell lines than MIAPACA cell line. Three compounds (12a, 12d and 12e) emerged as potent compounds with broad spectrum of cytotoxic activity against all the tested cell lines with GI50 values in the range of 0.01-2.1 μM. These compounds induce microtubule depolymerization and arrests cells at the G2/M phase of the cell cycle. Moreover, compounds 12d and 12e disrupted microtubule network and accumulated tubulin in the soluble fraction in a similar manner to their parent podophyllotoxin scaffold. In addition, structure activity relationship studies within the series were also discussed. Molecular docking studies of these compounds into the colchicine-binding site of tubulin, revealed possible mode of inhibition by these compounds.
• Formal synthesis of (−)-podophyllotoxin through the photocyclization of an axially chiral 3,4-bisbenzylidene succinate amide ester – a flow photochemistry approach
  作者：Kamil Lisiecki、Krzysztof K. Krawczyk、Piotr Roszkowski、Jan K. Maurin、Zbigniew Czarnocki

  DOI：10.1039/c5ob01844g

  日期：——

  We have developed a strategy for the stereoselective synthesis of cyclolignans related to podophyllotoxin and its derivatives. The crucial step of the synthesis is the photocyclization of a chiral atropoisomeric 1,2-bisbenzylidenesuccinate amide ester, which can be prepared from suitable aromatic aldehydes, diethyl succinate and L-prolinol. The photocyclization was found to be more efficient when irradiation

  我们已经开发了与鬼臼毒素及其衍生物有关的立体选择性合成环木脂体的策略。合成的关键步骤是手性阻转异构体1,2-双亚苄基琥珀酸酯酰胺酯的光环化，该酯可由合适的芳族醛，琥珀酸二乙酯和L-脯氨醇制备。当在自制的连续流光化学反应器中进行辐照时，发现光环化更有效。流入辐射还使我们能够以克数进行反应。用Schwartz试剂还原性裂解除去手性助剂，得到具有细胞毒性的1 R，2 R-顺式-鬼臼乙醛，可以轻松地将其还原为相应的醇，从而完成（-）-鬼臼毒素的正式合成。