(2E,6E)-2,6-bis(2,3,4-trimethoxybenzylidene)cyclohexanone | 1169991-45-0

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二芳基庚烷
• 英文名称: (2E,6E)-2,6-bis(2,3,4-trimethoxybenzylidene)cyclohexanone
• 英文别名: 2,6-bis((E)-2,3,4-trimethoxybenzylidene)cyclohexanone；(2E,6E)-2,6-bis[(2,3,4-trimethoxyphenyl)methylidene]cyclohexan-1-one
• CAS: 1169991-45-0
• 化学式: C₂₆H₃₀O₇
• 分子量: 454.52
• InChiKey: UXPJQPODQDLGGD-YXLFCKQPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  72.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  (2E,6E)-2,6-bis(2,3,4-trimethoxybenzylidene)cyclohexanone 在 ((4S)-2-(2-(diphenylphosphino)phenyl)-4-tert-butyl-4,5-dihydrooxazole)-(η4-1,5-cyclooctadiene)iridium(I) tetrakis(3,5-bis(trifluoromethyl)phenyl)borate 、 氢气 作用下， 以 二氯甲烷 为溶剂， 20.0 ℃ 、3.04 MPa 条件下， 反应 6.0h， 以94%的产率得到(-)-(2S,6S)-2,6-bis(2,3,4-trimethoxybenzyl)cyclohexanone
  参考文献：
  名称：

  手性环己基稠合螺二茚：实用合成、配体开发和不对称催化

  摘要：

  1,1'-螺二茚烷一直是手性配体设计的一种特殊骨架，1,1'-螺二茚满基手性配体在各种不对称催化中表现出优异的性能。然而，获得对映体纯螺二茚丹相当繁琐，阻碍了其实际应用。在本文中，通过一系列 Ir 催化的 α,α'-bis 不对称氢化，以高产率和优异的立体选择性（高达 > 99% ee）完成了环己基稠合手性螺二茚的简便对映选择性合成（亚芳基）酮和 TiCl4 促进了氢化手性酮的不对称螺环化。该协议可以在一锅中执行，并且易于扩展，并且已用于 25 g 规模的环己基稠合螺二茚二醇 (1 S, 2 S,2' S)-5，在 99% ee 和 67% 总产率的四个步骤中，无需色谱纯化。(1 S,2 S,2' S)-5 的简单衍生提供了直接获得手性单齿亚磷酰胺 6a-c 和三齿磷-酰氨基吡啶 11 的途径，它们在几个基准对映选择性反应（氢化、加氢酰化、和 [2 + 2] 反应）由过渡金属（Rh、Au 或

  DOI：

  10.1021/jacs.8b07125
• 作为产物：
  描述：

  环己酮 、 2,3,4-三甲氧基苯甲醛 在 sodium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 48.0h， 生成 (2E,6E)-2,6-bis(2,3,4-trimethoxybenzylidene)cyclohexanone
  参考文献：
  名称：

  Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors

  摘要：

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。

  DOI：

  10.1007/s11418-011-0568-0

文献信息

• Compound having chiral spirobiindane skeleton and preparation method therefor
  申请人：ZHEJIANG JIUZHOU PHARMACEUTICAL CO., LTD.

  公开号：US11325875B2

  公开（公告）日：2022-05-10

  Chiral spirobiindane skeleton compound and preparation method thereof is disclosed in the present invention. The spirobiindane skeleton compound of the present invention having the structure formula of I or I′; the preparation method for synthesizing the spirobiindane skeleton compound of the present invention comprising the following steps: in the presence of solvent and catalysts, the structure formula compound III reacted through intramolecular Friedel-Crafts reaction to obtain the compound of formula I; the catalyst is a Browsteric acidor Lewis acid. The preparation method of chiral fused spirobiindane skeleton compound of the present invention does not need to adopt chiral starting materials or chiral resolving agents, does not require chiral resolving steps, is simple in method, is simple in post-treatment, and is economic and environment friendly. High product yield, high product optical purity and chemical purity. The catalyst for the asymmetric reaction is obtained from the chiral spirobiindane skeleton ligand of the present invention, under the catalytic reagent of transition metal, the catalyzed hydrogenation reaction can arrive at a remarkable catalytic effect with a product yield of >99%, and a product ee value of up to >99%.

  本发明公开了手性螺茚满骨架化合物及其制备方法。本发明的螺茚二烷骨架化合物，其结构式为I或I′；合成本发明的螺茚二烷骨架化合物的制备方法包括以下步骤：在溶剂和催化剂存在下，结构式化合物III通过分子内Friedel-Crafts反应得到式I化合物；催化剂为Browsteric酸或Lewis酸。本发明手性融合螺双茚满骨架化合物的制备方法不需要采用手性起始原料或手性解析剂，不需要手性解析步骤，方法简单，后处理简单，经济环保。产品收率高，产品光学纯度和化学纯度高。不对称反应的催化剂由本发明的手性螺茚二烷骨架配体获得，在过渡金属的催化试剂作用下，催化加氢反应可达到显著的催化效果，产物收率>99%，产物ee值高达>99%。
• [EN] COMPOUND HAVING CHIRAL SPIROBIINDANE SKELETON AND PREPARATION METHOD THEREFOR<br/>[FR] COMPOSÉ PRÉSENTANT UN SQUELETTE SPIROBIINDANE CHIRAL ET SON PROCÉDÉ DE PRÉPARATION<br/>[ZH] 手性螺二氢茚骨架化合物及其制备方法
  申请人：ZHEJIANG JIUZHOU PHARM CO LTD

  公开号：WO2017107789A1

  公开（公告）日：2017-06-29

  本发明公开了一种手性螺二氢茚骨架化合物及其制备方法。本发明的手性稠环螺二氢茚骨架化合物如式I或I'所示；本发明的手性螺二氢茚骨架化合物的制备方法，其包括如下步骤：溶剂中，催化剂作用下，将如式III所示的化合物进行分子内傅里德-克拉夫茨反应，制得如式I所示的化合物；所述催化剂为布朗斯特酸或路易斯酸。本发明的制备方法，不需采用手性起始原料或手性拆分试剂、无须进行手性拆分步骤、方法简单、后处理简便、经济环保、产物收率高、产物光学纯度和化学纯度高。采用本发明的手性稠环螺二氢茚骨架化合物制得的过渡金属催化的不对称反应的催化剂，催化效果显著，产物收率＞99％，产物ee值高达＞99％。
• Activation of anti-oxidant Nrf2 signaling by enone analogues of curcumin
  作者：Lorraine M. Deck、Lucy A. Hunsaker、Thomas A. Vander Jagt、Lisa J. Whalen、Robert E. Royer、David L. Vander Jagt

  DOI：10.1016/j.ejmech.2017.11.048

  日期：2018.1

  Inflammation and oxidative stress are common in many chronic diseases. Targeting signaling pathways that contribute to these conditions may have therapeutic potential. The transcription factor Nrf2 is a major regulator of phase II detoxification and anti-oxidant genes as well as anti-inflammatory and neuroprotective genes. Nrf2 is widespread in the CNS and is recognized as an important regulator of brain inflammation. The natural product curcumin exhibits numerous biological activities including ability, to induce the expression of Nrf2-dependent phase II and anti-oxidant enzymes. Curcumin has been examined in a number of clinical studies with limited success, mainly owing to limited bioavailability and rapid metabolism. Enone analogues of curcumin were examined with an Nrf2 reporter assay to identify Nrf2 activators. Analogues were separated into groups with a 7-carbon dienone spacer, as found in curcumin; a 5-carbon enone spacer with and without a ring; and a 3-carbon enone spacer. Activators of Nrf2 were found in all three groups, many of which were more active than curcumin. Dose response studies demonstrated that a range of substituents on the aromatic rings of these enones influenced not only the sensitivity to activation, reflected in EC50 values, but also the extent of activation, which suggests that multiple mechanisms are involved in the activation of Nrf2 by these analogues. (C) 2017 Published by Elsevier Masson SAS.
• Synthesis and evaluation of curcumin-related compounds for anticancer activity
  作者：Xingchuan Wei、Zhi-Yun Du、Xi Zheng、Xiao-Xing Cui、Allan H. Conney、Kun Zhang

  DOI：10.1016/j.ejmech.2012.04.005

  日期：2012.7

  Sixty-one curcumin-related compounds were synthesized and evaluated for their anticancer activity toward cultured prostate cancer PC-3 cells, pancreas cancer Panc-1 cells and colon cancer HT-29 cells. Inhibitory effects of these compounds on the growth of PC-3. Panc-1 and HT-29 cells were determined by the MTT assay. Compounds E10, F10, FN1 and FN2 exhibited exceptionally potent inhibitory effects on the growth of cultured PC-3, Panc-1 and HT-29 cells. The IC50 for these compounds was lower than 1 mu M in all three cell lines. E10 was 72-, 46- and 117-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. F10 was 69-, 34- and 72-fold more active than curcumin for inhibiting the growth of PC-3, Panc-1 and HT-29 cells, respectively. FN1 and FN2 had about the same inhibitory effect as E10 and F10 toward Panc-1 cells but were less active than E10 and F10 toward PC-3 and HT-29 cells. The active compounds were potent stimulators of apoptosis. The present study indicates that E10, F10, FN1 and FN2 may have useful anticancer activity. (C) 2012 Elsevier Masson SAS. All rights reserved.
• Curcumin-like diarylpentanoid analogues as melanogenesis inhibitors
  作者：Takahiro Hosoya、Asami Nakata、Fumie Yamasaki、Faridah Abas、Khozirah Shaari、Nordin Hj Lajis、Hiroshi Morita

  DOI：10.1007/s11418-011-0568-0

  日期：2012.1

  Anti-melanogenesis screening of 47 synthesized curcumin-like diarylpentanoid analogues was performed to show that some had a potent inhibitory effect on the melanogenesis in B16 melanoma cells. Their actions were considered to be mostly due to tyrosinase inhibition, tyrosinase expression inhibition, and melanin pigment degradation. The structure–activity relationships of those curcumin-like diarylpentanoid analogues which inhibited the melanogenesis and tyrosinase activity were also discussed. Of those compounds assayed, (2E,6E)-2,6-bis(2,5-dimethoxybenzylidene)cyclohexanone showed the most potent anti-melanogenesis effect, the mechanism of which is considered to be the degradation of the melanin pigment in B16 melanoma cells, affecting neither the tyrosinase activity nor tyrosinase expression.

  对47种合成的姜黄素样二芳基戊烷类类似物进行了抗黑色素生成筛选，结果显示其中一些对B16黑色素瘤细胞的黑色素生成具有强抑制作用。这些作用主要被认为是通过抑制酪氨酸酶活性、抑制酪氨酸酶表达和降解黑色素色素实现的。还讨论了那些抑制黑色素生成和酪氨酸酶活性的姜黄素样二芳基戊烷类类似物的结构-活性关系。在测试的化合物中，（2E,6E）-2,6-双（2,5-二甲氧基苄叉）环己酮显示了最强的抗黑色素生成效果，其机制被认为是在B16黑色素瘤细胞中降解黑色素色素，既不影响酪氨酸酶活性也不影响酪氨酸酶表达。