(+/-)-di-O-methyl hexahydrocurcumin | 91998-04-8

• 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: (+/-)-di-O-methyl hexahydrocurcumin
• 英文别名: hexahydro-O,O-dimethyl-curcumin；Hexahydrocurcumin-di-O-methylester；3-Heptanone, 1,7-bis(3,4-dimethoxyphenyl)-5-hydroxy-；1,7-bis(3,4-dimethoxyphenyl)-5-hydroxyheptan-3-one
• CAS: 91998-04-8
• 化学式: C₂₃H₃₀O₆
• 分子量: 402.488
• InChiKey: NDVBVCMOGVYWMV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.4
• 重原子数：
  29
• 可旋转键数：
  12
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.43
• 拓扑面积：
  74.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  ASC-J9; 二甲基姜黄素 在 palladium on activated charcoal 氢气 作用下， 以 甲醇 为溶剂， 生成 (+/-)-di-O-methyl hexahydrocurcumin
  参考文献：
  名称：

  姜黄素在体外形成反应性葡糖醛酸。

  摘要：

  由于姜黄素具有抗炎，抗癌和抗阿尔茨海默氏病的活性，因此备受关注，但对其药代动力学和代谢命运知之甚少。因此，目前已经对姜黄素及其主要的I相代谢产物六氢姜黄素以及各种天然和人工类似物的葡糖醛酸苷化进行了体外研究。根据LC-MS / MS分析，由大鼠和人类肝脏微粒体由姜黄素，六氢姜黄素和其他具有酚羟基的类似物产生的主要葡萄糖醛酸苷为酚醛酸葡萄糖苷。然而，由人微粒体由相同的姜黄素而不是六氢姜黄素形成了在醇羟基上带有葡糖醛酸部分的第二葡糖醛酸。没有酚羟基的姜黄素仅产生脂族葡糖醛酸。姜黄素类的酚类葡糖醛酸而不是六氢姜黄素类的酚类葡糖醛酸具有相当的亲脂性，并且在水溶液中部分不稳定，其稳定性在很大程度上取决于芳族取代基的类型。姜黄素及其天然同源物的酚醛葡萄糖醛酸苷，而不是母体化合物，明显抑制了无细胞条件下微管蛋白的组装，暗示了葡糖醛酸苷的化学反应性。姜黄素主要II期代谢产物的这些新颖性质值得进一步研究。它

  DOI：

  10.1021/jf0623283

文献信息

• Syntheses of the (±)-[n]-gingerols (pungent principles of ginger) and related compounds through regioselective aldol condensations: relative pungency assays
  作者：Phillip Denniff、Ian Macleod、Donald A. Whiting

  DOI：10.1039/p19810000082

  日期：——

  has been found to be regioselective (92 : 8 in favour of less-substituted enolate): the anion was condensed with alkanals and acyl imidazoles to give convenient syntheses of the (±)-[2]–[10]- and -[12]-gingerols (1) and [4]-, [6]-, and [8]-gingerdiones (9). Similarly, 3-methoxy-4-trimethylsilyloxybenzylideneacetone (17) gave the (±)-[2]–[10]-dehydrogingerols (8) and [4]-, [6]-, and [8]-dehydrogingerdiones

  已发现在–78°C下用二异丙基氨基锂对三甲基甲硅烷基姜油酮（13）进行质子选择性（92：8，以取代基较少的烯酸酯为佳）：将阴离子与链烷烃和酰基咪唑缩合，以方便地合成（±）-[2]-[10]-和-[12]-姜醇（1）和[4]-，[6]-和[8]-姜二酮（9）。同样，3-甲氧基-4-三甲基甲硅烷基氧苄叉基丙酮（17）给出了（±）-[2]-[10]-脱氢姜油酚（8）和[4]-，[6]-和[8]-脱氢姜二酮（10）。 。
• Antitumor Agents. 250. Design and Synthesis of New Curcumin Analogues as Potential Anti-Prostate Cancer Agents
  作者：Li Lin、Qian Shi、Alexander K. Nyarko、Kenneth F. Bastow、Chin-Chung Wu、Ching-Yuan Su、Charles C.-Y Shih、Kuo-Hsiung Lee

  DOI：10.1021/jm051043z

  日期：2006.6.1

  In a continuing study of curcumin analogues as potential drug candidates to treat prostate cancer at both androgen-dependent and androgen-refractory stages, we designed and synthesized over 40 new analogues classified into four series: monophenyl analogues ( series A), heterocycle-containing analogues ( series B), analogues bearing various substituents on the phenyl rings ( series C), and analogues with various linkers ( series D). These new compounds were tested for cytotoxicity against two human prostate cancer cell lines, androgen-dependent LNCaP and androgen-independent PC-3. Antiandrogenic activity was also evaluated in LNCaP cells and PC-3 cells transfected with wild-type androgen receptor. Ten compounds possessed potent cytotoxicity against both LNCaP and PC-3 cells, seven only against LNCaP, and one solely against PC-3. This study established an advanced structure-activity relationship ( SAR), and these correlations will guide the further design of new curcumin analogues with better anti-prostate cancer activity.
• Curcuminoid analogs with potent activity against Trypanosoma and Leishmania species
  作者：Chatchawan Changtam、Harry P. de Koning、Hasan Ibrahim、M. Sohail Sajid、Matthew K. Gould、Apichart Suksamrarn

  DOI：10.1016/j.ejmech.2009.11.035

  日期：2010.3

  The natural curcuminoids curcumin (1), demethoxycurcumin (2) and bisdemethoxycurcumin (3) have been chemically modified to give 46 analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs and these parent curcuminoids and their analogs were assessed against protozoa of the Tryponosoma and Leishmania species. The parent curcuminoids exhibited low antitrypanosomal activity (EC50 for our drug-sensitive Trypanosoma brucei brucei line (WT) of compounds 1, 2 and 3 are 2.5, 4.6 and 7.7 mu M, respectively). Among 43 curcuminoid analogs and 8 pairs of 1: 1 mixture of curcuminoid analogs tested, 8 pure analogs and 5 isomeric mixtures of analogs exhibited high antitrypanosomal activity in sub-micromolar order of magnitude. Among these highly active analogs, 1,7-bis(4-hydroxy-3-methoxy-phenyl)hept-4-en-3-one (40) was the most active compound, with an EC50 value of 0.053 +/- 0.007 mu M; it was about 2-fold more active than the standard veterinary drug diminazene aceturate (EC50 0.12 +/- 0.01 mu M). Using a previously characterized diminazene-resistant T. b, brucei (TbAT1-KO) and a derived multi-drug resistant line (B48), no cross-resistance of curcuminoids was observed to the diamidine and melaminophenyl arsenical drugs that are the current treatments. Indeed, curcuminoids carrying a conjugated keto (enone) motif, including 40, were significantly more active against 7: b. brucei B48. This enone motif was found to contribute to particularly high trypanocidal activity against all Trypanosoma species and strains tested. The parent curcuminoids showed low antileishmanial activity (EC50 values of compounds 1 and 2 for Leishmania mexicana amastigotes are 16 +/- 3 and 37 +/- 6 mu M. respectively) while the control drug, pentamidine, displayed an EC50 of 16 +/- 2 mu M. Among the active curcuminoid analogs, four Compounds exhibited EC50 values of less than 5 mu M against Leishmania major promastigotes and four against L mexicana amastigotes. No significant difference in sensitivity to curcuminoids between L. major promastigotes and L. mexicana amastigotes was observed. The parent curcuminoids and most of their analogs were also tested for their toxicity against human embryonic kidney (HEK) cells. All the curcuminoids exhibited lower toxicity to HEK cells than to T b. brucei bloodstream forms and only one of the tested compounds showed significantly higher activity against HEK cells than curcumin (1). The selectivity index for T b. brucei ranged from 3-fold to 1500-fold. The selectivity index for the most active analog, the enone 40, was 453-fold. (C) 2009 Elsevier Masson SAS. All rights reserved.
• Antitumor Agents. 217. Curcumin Analogues as Novel Androgen Receptor Antagonists with Potential as Anti-Prostate Cancer Agents
  作者：Hironori Ohtsu、Zhiyan Xiao、Junko Ishida、Masahiro Nagai、Hui-Kang Wang、Hideji Itokawa、Ching-Yuan Su、Charles Shih、Tzuying Chiang、Eugene Chang、Lee、Meng-Yin Tsai、Chawnshang Chang、Kuo-Hsiung Lee

  DOI：10.1021/jm020200g

  日期：2002.11.1

  A number of curcumin analogues were prepared and evaluated as potential androgen receptor antagonists against two human prostate cancer cell lines, PC-3 and DU-145, in the presence of androgen receptor (AR) and androgen receptor coactivator, ARA70. Compounds 4 [5-hydroxy-1,7-bis(3,4-dimethoxyphenyl)-1,4,6-heptatrien-3-one], 20 [5-hydroxy-1,7-bis[3-methoxy-4-(meth-oxycarbonylmethoxy)phenyl]-1,4,6-heptatrien-3-one], 22 [7-(4-hydroxy-3-methoxyphenyl)-4-[3(4-hydroxy-3-methoxyphenyl)acryloyl]-5-oxohepta-4,6-dienoic acid ethyl ester], 23 [7-(4-hydroxy-3-methoxyphenyl)-4-[3-(4-hydroxy-3-methoxyphenyl)acryloyl]5-oxohepta-4,6-dienoic acid], and 39 [bis(3,4-dimethoxyphenyl)-1,3-propanedione] showed potent antiandrogenic activities and were superior to hydroxyflutamide, which is the currently available antiandrogen for the treatment of prostate cancer. Structure-activity relationship (SAR) studies indicated that the bis(3,4-dimethoxyphenyl) moieties, the conjugated beta-diketone moiety, and the intramolecular symmetry of the molecules seem to be important factors related to antiandrogenic activity. The data further suggest that the coplanarity of the beta-diketone moiety and the presence of a strong hydrogen bond donor group were also crucial for the antiandrogenic activity, which is consistent with previous SAR results for hydroxyflutamide analogues. When the pharmacophoric elements of dihydrotestosterone (DHT) and compound 4 are superposed, the resulting construct implies that the curcumin analogues may function as a 17alpha-substituted DHT. Compounds 4, 20, 22, 23, and 39 have been identified as a new class of antiandrogen agents, and these compounds or their new synthetic analogues could be developed into clinical trial candidates to control androgen receptor-mediated prostate cancer growth.
• Curcuminoids Form Reactive Glucuronides In Vitro
  作者：Erika Pfeiffer、Simone I. Hoehle、Stephan G. Walch、Alexander Riess、Anikó M. Sólyom、Manfred Metzler

  DOI：10.1021/jf0623283

  日期：2007.1.1

  the glucuronic acid moiety at the alcoholic hydroxyl group was formed from the same curcuminoids, but not hexahydro-curcuminoids, by human microsomes. Curcuminoids without a phenolic hydroxyl group gave rise to the aliphatic glucuronide only. The phenolic glucuronides of curcuminoids, but not of hexahydro-curcuminoids, were rather lipophilic and, in part, unstable in aqueous solution, their stability

  由于姜黄素具有抗炎，抗癌和抗阿尔茨海默氏病的活性，因此备受关注，但对其药代动力学和代谢命运知之甚少。因此，目前已经对姜黄素及其主要的I相代谢产物六氢姜黄素以及各种天然和人工类似物的葡糖醛酸苷化进行了体外研究。根据LC-MS / MS分析，由大鼠和人类肝脏微粒体由姜黄素，六氢姜黄素和其他具有酚羟基的类似物产生的主要葡萄糖醛酸苷为酚醛酸葡萄糖苷。然而，由人微粒体由相同的姜黄素而不是六氢姜黄素形成了在醇羟基上带有葡糖醛酸部分的第二葡糖醛酸。没有酚羟基的姜黄素仅产生脂族葡糖醛酸。姜黄素类的酚类葡糖醛酸而不是六氢姜黄素类的酚类葡糖醛酸具有相当的亲脂性，并且在水溶液中部分不稳定，其稳定性在很大程度上取决于芳族取代基的类型。姜黄素及其天然同源物的酚醛葡萄糖醛酸苷，而不是母体化合物，明显抑制了无细胞条件下微管蛋白的组装，暗示了葡糖醛酸苷的化学反应性。姜黄素主要II期代谢产物的这些新颖性质值得进一步研究。它