2-<4-Brom-phenyl>-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diethylester | 4759-57-3

• 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-Brom-phenyl>-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diethylester
• 英文别名: 2-(4-Brom-phenyl)-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diethylester；Diethyl 2-(4-bromophenyl)-4-hydroxy-4-methyl-6-oxocyclohexane-1,3-dicarboxylate
• CAS: 4759-57-3
• 化学式: C₁₉H₂₃BrO₆
• mdl: MFCD00521058
• 分子量: 427.292
• InChiKey: NTNFVQUAJMSDFP-UHFFFAOYSA-N

物化性质

• 熔点：
  150-151 °C
• 沸点：
  518.1±50.0 °C(Predicted)
• 密度：
  1.391±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  26
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.526
• 拓扑面积：
  89.9
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-<4-Brom-phenyl>-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diethylester 在 一水合肼 作用下， 以 乙醇 为溶剂， 反应 12.0h， 生成 ethyl 4-(4-bromophenyl)-6-hydroxy-6-methyl-3-oxo-2,3,4,5,6,7-hexahydro-1H-indazole-5-carboxylate
  参考文献：
  名称：

  Catalysis by Amberlyst A-21: A Greener Approach to 4,5,6,7-Tetrahydro-1H-indazol-3(2H)-ones via Construction of Cyclohexanones

  摘要：

  The 4,5,6,7-tetrahydro-1H-indazol-3(2H)-one derivatives have been synthesized in good yields via a two-step method in a single pot. The initial step involved the construction of cyclohexanone ring from aromatic aldehydes and beta-ketoester in i-PrOH using an inexpensive and reusable catalyst (i.e., Amberlyst A-21) under mild reaction conditions. The utility of this catalyst has been demonstrated in synthesizing a range of cyclohexanone derivatives. The catalyst can be recovered and recycled, which makes this procedure simple, convenient, economically viable, and environmental friendly. [Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications (R) for the following free supplemental resource(s): Full experimental and spectral details.]

  DOI：

  10.1080/00397911.2013.844260
• 作为产物：
  描述：

  乙酰乙酸乙酯 、 对溴苯甲醛 在 Indion 860 作用下， 以 乙醇 为溶剂， 反应 15.0h， 以91%的产率得到2-<4-Brom-phenyl>-4-hydroxy-4-methyl-6-oxo-cyclohexan-1,3-dicarbonsaeure-diethylester
  参考文献：
  名称：

  Indion 860 catalyzed cascade reaction: a greener approach to functionalized cyclohexanones and their novel analogues

  摘要：

  通过 Indion 860 介导的β-酮酯或 1,3-二酮与烷基/芳基/杂芳基醛的级联反应，可在露天条件下生成官能化环己酮。催化剂可以回收和循环使用。将这一方法与同一锅中的其他反应相结合，可以得到多种多样的新型分子。一些合成的化合物在体外显示出对 PDE4 的抑制作用。

  DOI：

  10.1039/c2ra23039a

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。
• Syntheses and some features of five new cyclohexane-1,3-dicarboxylates with multiple stereogenic centers
  作者：Arif M. Ismiyev、Abel M. Maharramov、Rafiga A. Aliyeva、Rizvan K. Askerov、Kamran T. Mahmudov、Maximilian N. Kopylovich、Houcine Naïli、Armando J.L. Pombeiro

  DOI：10.1016/j.molstruc.2012.08.006

  日期：2013.1

  only cyclohexanone carbonyl moiety undergoes the transformation, leaving the β-keto ester carbonyls unreacted. Withing the compounds 1 – 5 , the increase in the Hammett’s σ p , related normal σ p n , inductive σ I , negative σ p - and positive σ p + polar conjugation and Taft’s σ p o substituent constants generally leads to the corresponding drift of δ O H and δ N H NMR chemical shifts to lower field

  摘要 4-羟基-4-甲基-6-氧代-2-(4-取代苯基)-环己烷-1,3-二羧酸二乙酯与N'-(2-氯丙基)乙烷-1,2-二胺缩合得到1-(2-氯丙基)-9-羟基-9-甲基-7-苯基-1,4-二氮杂螺[4.5]癸烷-6,8-二羧酸二乙酯(2)及其对位取代甲基(1)、氯( 3 )、溴 ( 4 ) 和硝基 ( 5 ) 衍生物具有新的立体中心，通过元素分析、ESI-MS、IR、 1 H 和 13 C NMR 光谱和 X 射线单晶分析进行了充分表征（对于 2 ）。缩合反应是区域选择性的，只有环己酮羰基部分发生转化，留下未反应的 β-酮酯羰基。对于化合物 1 – 5，哈米特的 σ p 增加，相关法向 σ pn ，归纳 σ I ，