2-(2,4-Dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diaethylester | 64670-39-9

• 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-(2,4-Dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diaethylester
• 英文别名: 2-(3,4-dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexane-1,3-dicarboxylic acid diethyl ester；2-(3,4-Dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diaethylester；4-Hydroxy-6-oxo-4-methyl-2-(3,4-dimethoxy-phenyl)-cyclohexan-dicarbonsaeure-(1,3)-diaethylester；Diethyl 2-(3,4-dimethoxyphenyl)-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate
• CAS: 64670-39-9
• 化学式: C₂₁H₂₈O₈
• mdl: MFCD00718104
• 分子量: 408.449
• InChiKey: SSFQCYJOBBZRIP-UHFFFAOYSA-N

物化性质

• 熔点：
  138.5-140.5 °C
• 沸点：
  531.3±50.0 °C(Predicted)
• 密度：
  1.205±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.2
• 重原子数：
  29
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.57
• 拓扑面积：
  108
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  2-(2,4-Dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diaethylester 在 sodium hydroxide 作用下， 生成 5-(3,4-dimethoxy-phenyl)-3-methyl-cyclohex-2-enone
  参考文献：
  名称：

  Triton B in Synthesis of 3-Phenylcyclohexenones

  摘要：

  DOI：

  10.1021/ja01618a081
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 3,4-二甲氧基苯甲醛 在 哌啶 作用下， 生成 2-(2,4-Dimethoxy-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diaethylester
  参考文献：
  名称：

  罗汉松科的化学—十五：罗汉松酸的精制

  摘要：

  描述了将二萜树脂酸，罗汉果酸转化为具有5元环D的四环体系。由13-（2'-羧乙基）衍生物III（RCH 2 CH 2 CO 2 H）以合理的产率制备了在C-15 1处带有CO基团的未取代环，但尝试将具有1'的化合物环化C-13的-取代的2'-羧乙基侧链不成功。从13-丙烯酰基化合物以低收率获得C-17酮，但从13-巴豆酰基化合物根本得不到。描述了一些涉及苯甲醚衍生物的模型实验。

  DOI：

  10.1016/0040-4020(68)88118-9

文献信息

• Effect of Aryl-Cyclohexanones and their Derivatives on Macrophage Polarization In Vitro
  作者：Tainá L. Lubschinski、Luiz A. E. Pollo、Eduarda T. B. Mohr、Julia S. da Rosa、Luigi A. Nardino、Louis P. Sandjo、Maique W. Biavatti、Eduardo M. Dalmarco

  DOI：10.1007/s10753-022-01646-9

  日期：2022.8

  Macrophages are critical in both tissue homeostasis and inflammation, and shifts in their polarization have been indicated as pivotal for the resolution of inflammatory processes. Inflammation is a complex and necessary component of the immune response to stimuli that are harmful to host homeostasis and is regulated by cellular and molecular events that remain a source of ongoing investigation. Among the compounds studied that have potential against autoimmune and inflammatory diseases, cannabinoids are currently highlighted. In this work, nineteen aryl-cyclohexanones diesters and their derivatives were synthesized based on the aryl-cyclohexane skeleton of phytocannabinoids, such as cannabidiol (CBD), and were evaluated for their anti-inflammatory and macrophage polarization potential. The results showed that Compound 4 inhibited the production of nitric oxide in RAW 264.7 macrophages. Furthermore, it reduced the levels of pro-inflammatory cytokines IL-12p70, TNF-α, IFN-γ, MCP-1, and IL-6 while, at the same time, was able to increase the production of anti-inflammatory cytokines IL-4, IL-10, and IL-13. Compound 4 also reduced macrophage apoptosis, increased the expression of the CD206 (mannose receptor) and at the same time, decreased the expression of CD284 (TLR-4 receptor) on the surface of these cells. Finally, it increased the phagocytic capacity and inhibited the phosphorylation of the p65 of NF-kβ. In conclusion, Compound 4, identified as diethyl-4-hydroxy-2-(4-methoxyphenyl)-4-methyl-6-oxocyclohexane-1–3-dicarboxylate, showed significant anti-inflammatory effect, while demonstrating the ability to transform phenotypically macrophages from the M1 phenotype (pro-inflammatory) to the M2 phenotype (anti-inflammatory). This led us to hypothesize that the main mechanism of anti-inflammatory effect of this molecule is linked to its immune modulation capacity.

  巨噬细胞在组织稳态和炎症过程中都起着至关重要的作用，其极化的变化被认为是解决炎症过程的关键。炎症是免疫反应的一个复杂而必要的组成部分，它针对的是对宿主稳态有害的刺激，并受到细胞和分子事件的调节，而这些事件仍是研究的一个来源。在已研究的具有抗自身免疫性和炎症性疾病潜力的化合物中，大麻素是目前研究的重点。本研究以大麻二酚（CBD）等植物大麻素的芳基环己烷骨架为基础，合成了 19 种芳基环己酮二酯及其衍生物，并对其抗炎和巨噬细胞极化潜力进行了评估。结果表明，化合物 4 能抑制 RAW 264.7 巨噬细胞产生一氧化氮。此外，它还能降低促炎细胞因子 IL-12p70、TNF-α、IFN-γ、MCP-1 和 IL-6 的水平，同时还能增加抗炎细胞因子 IL-4、IL-10 和 IL-13 的产生。化合物 4 还能减少巨噬细胞凋亡，增加这些细胞表面 CD206（甘露糖受体）的表达，同时减少 CD284（TLR-4 受体）的表达。最后，它还提高了吞噬能力，抑制了 NF-kβ 的 p65 的磷酸化。总之，被鉴定为二乙基-4-羟基-2-（4-甲氧基苯基）-4-甲基-6-氧代环己烷-1-3-二甲酸酯的化合物 4 显示出了显著的抗炎效果，同时还显示出了将巨噬细胞从 M1 表型（促炎）转化为 M2 表型（抗炎）的能力。由此我们推测，该分子抗炎作用的主要机制与其免疫调节能力有关。
• Aromatization Studies. IV. Palladium Dehydrogenation of Arylcyclohexenones to Phenols
  作者：E. C. Horning、M. G. Horning

  DOI：10.1021/ja01198a035

  日期：1947.6
• THE CHEMOTHERAPY OF CANCER. II. SOME ARYL-SUBSTITUTED ALKOXYMETHYLENE CYCLOHEXENONES^{1, 2}
  作者：KENNETH N. CAMPBELL、ALBERT SCHRAGE、BARBARA K. CAMPBELL

  DOI：10.1021/jo01152a002

  日期：1950.11
• LAL B.; BHADURI A. P., INDIAN J. CHEM. <IJOC-P>, 1977, B 15, NO 4, 359-363
  作者：LAL B.、 BHADURI A. P.

  DOI：——

  日期：——
• Chemistry of the podocarpaceae—XV
  作者：B.R. Davis、W.B. Watkins

  DOI：10.1016/0040-4020(68)88118-9

  日期：1968.1

  The conversion of the diterpenoid resin acid, podocarpic acid, into a tetracyclic system possessing a 5-membered ring D is described. The unsubstituted ring with a CO group at C-151 was prepared from the 13-(2′-carboxyethyl) derivative III (R  CH2CH2CO2H) in fair yield, but attempted cyclization of compounds possessing a 1′-substituted-2′-carboxyethyl side chain at C-13 was unsuccessful. The C-17

  描述了将二萜树脂酸，罗汉果酸转化为具有5元环D的四环体系。由13-（2'-羧乙基）衍生物III（RCH 2 CH 2 CO 2 H）以合理的产率制备了在C-15 1处带有CO基团的未取代环，但尝试将具有1'的化合物环化C-13的-取代的2'-羧乙基侧链不成功。从13-丙烯酰基化合物以低收率获得C-17酮，但从13-巴豆酰基化合物根本得不到。描述了一些涉及苯甲醚衍生物的模型实验。