2,4,5-trimethoxy-3,6-dimethylbenzaldehyde | 92421-47-1

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 2,4,5-trimethoxy-3,6-dimethylbenzaldehyde
• 英文别名: 2,5-dimethyl-1,3,4-trimethoxybenzaldehyde；2,5-dimethyl-3,4,6-trimethoxybenzaldehyde；Benzaldehyde, 2,4,5-trimethoxy-3,6-dimethyl-
• CAS: 92421-47-1
• 化学式: C₁₂H₁₆O₄
• 分子量: 224.257
• InChiKey: CKQVIVNVLKSGMC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2
• 重原子数：
  16
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.42
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2,4,5-trimethoxy-3,6-dimethylbenzaldehyde 在 sodium hydroxide 、 ammonium cerium(IV) nitrate 、 sodium hydride 作用下， 以 乙醇 、 水 、 乙腈 为溶剂， 反应 2.5h， 生成 (E)-3-(2-methoxy-3,6-dimethyl-1,4-benzoquinon-5-yl)-2-[5-(pyridin-3-yl)pentyl]-2-propenoic acid
  参考文献：
  名称：

  Structure−Activity Relationships of (E)-3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase

  摘要：

  As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A(2) synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) Bq and TXA(2) while not significantly inhibiting that of prostaglandin E(2) by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB(4) and TXB(2) production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB(4) production. The position of an alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA(2) synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA(2) synthetase and possess a variety of pharmacologically beneficial effects.

  DOI：

  10.1021/jm950725r
• 作为产物：
  描述：

  2,5-dimethoxy-3,6-dimethylphenol 在 四氯化钛 、 sodium hydride 作用下， 反应 6.0h， 生成 2,4,5-trimethoxy-3,6-dimethylbenzaldehyde
  参考文献：
  名称：

  Structure−Activity Relationships of (E)-3-(1,4-Benzoquinonyl)-2-[(3-pyridyl)- alkyl]-2-propenoic Acid Derivatives That Inhibit Both 5-Lipoxygenase and Thromboxane A₂ Synthetase

  摘要：

  As part of our research for the development of novel antiinflammatory drug candidates, we have designed and synthesized a series of (E)-3-(1,4-benzoquinonyl)-2-[(3-pyridyl)alkyl]-2-propenoic acid derivatives as dual inhibitors of 5-lipoxygenase (5-LO) and thromboxane (TX) A(2) synthetase. In order to increase the absorption after oral administration, we introduced a carboxylic acid moiety into the 1,4-benzoquinone skeleton, which has 5-LO-inhibitory character. Introduction of a 3-pyridylalkyl group at the double bond of the 1,4-benzoquinonyl propenoic acid moiety afforded good to moderate inhibitory activities against the production of leukotriene (LT) Bq and TXA(2) while not significantly inhibiting that of prostaglandin E(2) by glycogen-induced peritoneal cells of rat (in vitro). The length of the methylene chain of the 3-pyridylalkyl group influenced the inhibition of LTB(4) and TXB(2) production. An increase of lipophilicity by introducing a more lipophilic alkoxy group did not markedly increase the inhibitory activity on LTB(4) production. The position of an alkoxy group on the 1,4-benzoquinone skeleton played an important role in TXA(2) synthetase inhibition. Compounds such as 20c (E6700) with an appropriate alkoxy group and proper length of methylene side chain, together with a polar substituent (carboxylic acid), showed good inhibition of both 5-LO and TXA(2) synthetase and possess a variety of pharmacologically beneficial effects.

  DOI：

  10.1021/jm950725r

文献信息

• Total Synthesis of Hybocarpone and Analogues Thereof. A Facile Dimerization of Naphthazarins to Pentacyclic Systems
  作者：K. C. Nicolaou、David L. F. Gray

  DOI：10.1021/ja030497n

  日期：2004.1.1

  The total synthesis of the lichen-derived antitumor agent hybocarpone (1) and related compounds is described. The successful route to hybocarpone features a novel radical-based dimerization/hydration cascade which generates the bridging hindered carbon-carbon bond of the molecule in a stereocontrolled manner, setting the relative configurations of the four contiguous stereocenters in a single step

  描述了地衣衍生的抗肿瘤剂 Hybocarpone (1) 和相关化合物的全合成。Hybocarpone 的成功途径具有一种新型的基于自由基的二聚化/水合级联，它以立体控制的方式产生分子的桥接受阻碳 - 碳键，在一个步骤中设置四个连续立体中心的相对构型。推测该过程可能与导致自然界中hybocarpone形成的生物合成途径没有太大不同。这些分子框架的开发序列还具有合成有用的 Diels-Alder 捕获光化学生成的羟基-o-醌二甲烷物种与 1,1-二取代烯烃以形成季中心的第一个例子，
• Construction of polycyclic structures with vicinal all-carbon quaternary stereocenters <i>via</i> an enantioselective photoenolization/Diels–Alder reaction
  作者：Min Hou、Mengmeng Xu、Baochao Yang、Haibing He、Shuanhu Gao

  DOI：10.1039/d1sc00883h

  日期：——

  present in one molecule, they will dramatically increase its synthetic challenge. A chiral titanium promoted enantioselective photoenolization/Diels–Alder (PEDA) reaction allows largely stereohindered tetra-substituted dienophiles to interact with highly active photoenolized hydroxy-o-quinodimethanes, delivering fused or spiro polycyclic rings bearing vicinal all-carbon quaternary centers in excellent

  全碳四元立构中心在天然产物中普遍存在，并且在药物分子中具有重要意义。然而，由于化学环境拥挤，全碳立构中心的构建是一个具有挑战性的项目。而且，当一个分子中存在邻位全碳四元立构中心时，它们将极大地增加其合成挑战。手性钛促进的对映选择性光烯醇化/狄尔斯-阿尔德（PEDA）反应允许很大程度上立体受阻的四取代亲二烯体与高活性光烯醇化羟基-邻醌二甲烷相互作用，以优异的对映体过量提供带有邻位全碳四元中心的稠合或螺环多环通过一步操作。这种新开发的对映选择性 PEDA 反应将激发不对称激发态反应的其他进展，并可用于结构相关的复杂天然产物或药物分子的全合成，以进行药物发现。
• Total Synthesis of Hamigerans and Analogues Thereof. Photochemical Generation and Diels−Alder Trapping of Hydroxy-<i>o</i>-quinodimethanes
  作者：K. C. Nicolaou、David L. F. Gray、Jinsung Tae

  DOI：10.1021/ja030498f

  日期：2004.1.1

  and subsequent Diels-Alder (PEDA) trapping of the generated hydroxy-o-quinodimethanes, this method was optimized to set the stage for the total synthesis of several naturally occurring members of the hamigeran class. Specifically, the developed synthetic technology served as the centerpiece process for the successful asymmetric synthesis of hamigerans A (2), B (3), and E (7). In addition to the PEDA reactions

  许多天然存在的物质，包括hamigerans，包含与芳香核稠合的环系统。已经开发了一种用于构建这种苯并环双环和多环碳框架的通用和简化的方法，并探讨了其范围和局限性。在取代苯甲醛的光烯醇化和随后的狄尔斯-阿尔德 (PEDA) 捕获生成的羟基-o-醌二甲烷的基础上，优化了该方法，为几种天然存在的 hamigeran 类成员的全合成奠定了基础。具体而言，开发的合成技术是成功不对称合成 hamigerans A (2)、B (3) 和 E (7) 的核心过程。除了 PEDA 反应外，还描述了其他几种新的反应过程，包括高产率的脱羰环收缩和羟基β-酮酯的氧化脱羧以提供α-二酮。这些具有生物活性的天然产物的许多类似物也通过应用开发的技术制备。
• 一种合成含季碳中心的并环化合物的方法
  申请人：华东师范大学

  公开号：CN107868102B

  公开（公告）日：2020-08-11

  本发明公开了一种合成含季碳中心的并环化合物的方法，所述方法包括如下反应：即：由式a所示的芳香醛与式b所示的环形亲双烯体在紫外光或可见光的光照下及路易斯酸的作用下进行环化反应，从而得到式c所示的目标物。本发明通过创造性地由芳香醛与环形亲双烯体在紫外光或可见光的光照下及路易斯酸的作用下进行环化反应，从而合成得到含季碳中心的并环化合物，所述方法具有操作简单、原料易得、安全环保、反应条件温和、重复性好及易于实现规模化生产等优点，对促使具有季碳中心的并环化合物的活性研究和工业化应用具有重要意义。
• 一类六环系甾体衍生物及其合成方法
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  公开号：CN107868116B

  公开（公告）日：2021-02-26

  本发明公开了一类六环系甾体衍生物及其合成方法，所述的六环系甾体衍生物是具有如下化学结构通式的化合物：所述的合成方法包括如下反应：即：式c所示的目标六环系甾体衍生物是由式a所示的芳香醛与式b所示的甾体化合物在紫外光或可见光的光照下及路易斯酸的作用下进行环化反应得到。本发明提供的六环系甾体衍生物具有多种官能团，易于实现进一步衍生化反应，可为后续筛选活性甾体药物提供庞大的化合物库，对甾体药物的研究具有显著价值；并且，本发明所述合成方法具有操作简单、原料易得、安全环保、反应条件温和、重复性好及易于实现规模化生产等优点。