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 ，
• Catalysis by Amberlyst A-21: A Greener Approach to 4,5,6,7-Tetrahydro-1H-indazol-3(2<i>H</i>)-ones via Construction of Cyclohexanones
  作者：Manam Sreenivasa Rao、Meda Haritha、Sunder Kumar Kolli、Mandava V. Basaveswara Rao、Manojit Pal

  DOI：10.1080/00397911.2013.844260

  日期：2014.4.18

  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.]
• Indion 860 catalyzed cascade reaction: a greener approach to functionalized cyclohexanones and their novel analogues
  作者：T. Bhaskar Kumar、G. Dhananjaya、Ch. Sumanth、S. Vaishaly、Gajanan Botre、M. Srinivasa Rao、K. B. Chandra Sekhar、K. Shiva Kumar、Manojit Pal

  DOI：10.1039/c2ra23039a

  日期：——

  An Indion 860 mediated cascade reaction of β-ketoester or 1,3-diketone with alkyl/aryl/heteroaryl aldehydes afforded functionalized cyclohexanones in the open air. The catalyst can be recovered and recycled. Combining this methodology with other reactions in the same pot afforded diversity based novel molecules. Some of the synthesized compounds showed inhibition of PDE4 in vitro.

  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。