4,4'-di-O-(β-D-glucopyranosyl)curcumin

• 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: 4,4'-di-O-(β-D-glucopyranosyl)curcumin
• 英文别名: curcumin-1-O,2-O-diglucopyranoside；curcumin β-D-glucoside；diglucosylcurcumin；curcumin di-O-glucoside；(1E,6E)-1,7-bis[3-methoxy-4-[(2S,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyphenyl]hepta-1,6-diene-3,5-dione
• 化学式: C₃₃H₄₀O₁₆
• 分子量: 692.671
• InChiKey: UZHDXKSOQKQWPH-KTQQPIDFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  49
• 可旋转键数：
  14
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  251
• 氢给体数：
  8
• 氢受体数：
  16

反应信息

• 作为反应物：
  描述：

  4,4'-di-O-(β-D-glucopyranosyl)curcumin 、 二氯(1,10-亚铁试剂)铂(II) 、 silver nitrate 在 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 29.0h， 以30%的产率得到[Pt(phen)(scur)](NO₃)
  参考文献：
  名称：

  葡萄糖附加姜黄素和生物素化的1,10-菲咯啉的光致细胞毒性癌细胞靶向铂（II）配合物

  摘要：

  混合配体铂（II）配合物[Pt（phen）（pacac）] [NO 3）（1），[Pt（phen）（cur）] [NO 3）（2），[Pt（bt-phen） （cur）]（NO 3）（3）和[Pt（phen）（scur）]（NO 3）（4），其中phen是1,10-菲咯啉，bt-phen是5-biotin-1,10-制备并表征了菲咯啉，pacac为1,3-二苯基-1,3-丙二酸根阴离子，Hcur为姜黄素，Hscur为二葡萄糖基姜黄素。配合物2-4显示的吸收带在410-430 nm（ε，2.1×10 4至2.8×10 4 M -1 cm-1）在10％DMSO-DPBS（靠近530纳米的Dulbecco氏磷酸盐缓冲盐水）和发射带（ λ EX与荧光量子产率= 410-430纳米）（ Φ ˚F）的~0.02值。姜黄素复合物在48小时的研究时间内显示出稳定性。使用人宫颈HeLa，人肝HepG2，人乳腺癌MDA-MB

  DOI：

  10.1039/c9dt03490k
• 作为产物：
  描述：

  2,3,4,6-四邻乙酰基-alpha-d-吡喃葡萄糖氯化物 在 吡啶 、 氨 作用下， 以 甲醇 为溶剂， 反应 5.0h， 生成 4,4'-di-O-(β-D-glucopyranosyl)curcumin
  参考文献：
  名称：

  Design, development and synthesis of mixed bioconjugates of piperic acid–glycine, curcumin–glycine/alanine and curcumin–glycine–piperic acid and their antibacterial and antifungal properties

  摘要：

  In the present communication different curcumin bioconjugates viz. 4,4'-di-O-glycinoyl-curcumin, 4,4'-di-O-D-alaninoyl-curcumin, 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin, 4,4'-di-O-piperoyl curcumin, curcumin-4,4'-di-O-P-D-glucopyranoside, 4,4'-di-O-acetyl-curcumin along with piperoyl glycine, have been synthesised and characterised by spectra UV, H-1 NMR and elemental analysis. All the covalent bonds used are biodegradable. This makes these derivatives as potent prodrugs, which can get hydrolysed at the target sites. These bioconjugates were tested in vitro against different bacteria and fungi. The 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin and 4,4'-di-O-acetyl-curcumin are more effective than Cefepime, an antibacterial drug available in market, at the same concentration. The 4,4'-di-O-(glycinoyl-di-N-piperoyl)-curcumin and 4,4'-di-O-piperoyl curcumin had antifungal activity in vitro almost comparable with fluconazole, the most popular antifungal drug. The enhanced activity of these bioconjugates vis-A-vis the parent molecule that is curcumin may be due to improved cellular uptake or reduced metabolism of these bioconjugates resulting in building up of enough concentration inside the infected cells. It opens a new era for exploring suitably designed curcurnin bioconjugates as potential antibacterial/antifungal drugs. (C) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2004.12.057

文献信息

• Regio- and Stereospecific<i>O</i>-Glycosylation of Phenolic Compounds Catalyzed by a Fungal Glycosyltransferase from<i>Mucor hiemalis</i>
  作者：Jin Feng、Peng Zhang、Yinglu Cui、Kai Li、Xue Qiao、Ying-Tao Zhang、Shu-Ming Li、Russell J. Cox、Bian Wu、Min Ye、Wen-Bing Yin

  DOI：10.1002/adsc.201601317

  日期：2017.3.20

  promiscuity of the new phenolic O‐glycosyltransferase was explored by using phenols from Traditional Chinese Medicinal herbs as substrates. MhGT1 exhibited robust capabilities for the regio‐ and stereospecific O‐glycosylation of 72 structurally diverse drug‐like scaffolds and sterols with uridine diphosphate (UDP) glucose as a sugar donor. Unprecedentedly, MhGT1 showed higher regiospecificities and activities

  糖基化的小分子通常具有生物活性，主要通过微生物的生物转化（尤其是真菌）获得。但是，丝状真菌中尚未发现负责任的糖基化基因/酶。我们在这里报告的第一个鉴定的酚糖基转移酶MhGT1来自毛藻。以中国传统中草药中的酚类为底物，探索了新型酚O-糖基转移酶的底物混杂性。MhGT1具有针对区域和立体定向O的强大功能用尿苷二磷酸（UDP）葡萄糖作为糖供体对72种结构多样的药物样支架和固醇进行糖基化。前所未有地，MhGT1对异戊烯基酚显示出更高的区域特异性和活性，而对非异戊烯基化类似物而言。MhGT1的计算模型发现了酶的N端截短的结构域，该结构域由疏水性和带电荷的氨基酸残基组成，这有助于宽泛的底物范围和对异戊二烯基化合物的区域特异性。我们的发现扩展了获得新糖基转移酶的方法，并在药物发现中有效地应用了酶法来获得糖基化化合物。
• Investigation of therapeutic effect of curcumin α and β glucoside anomers against Alzheimer’s disease by the nose to brain drug delivery
  作者：Nahid Ahmadi、Mir-Jamal Hosseini、Kobra Rostamizadeh、Mahdieh Anoush

  DOI：10.1016/j.brainres.2021.147517

  日期：2021.9

  were used to administer different treatments. They divided into control, sham, Alzheimer, and test groups (Alzheimer + α anomer and Alzheimer + β anomer). Animals received normal saline, Scopolamine (1 mg/kg), high dose anomers, scopolamine, and two doses (12.5 and 25 mg/kg) of anomers, respectively, for 10 days. Then the Morris Water Maze (MWM) test was performed on all animals. Finally, the animals’

  阿尔茨海默病 (AD) 是本世纪最大的老年医学挑战之一，也是导致痴呆的主要疾病。尽管科学研究取得了广泛的进展，但可用的改善疾病的治疗策略仍然有限；因此，对新药的需求增加。近年来，药用植物因其在痴呆中的潜在作用而受到关注。在本研究中，合成了姜黄素糖苷 (CGs) 的 α 和 β 端基异构体，并对其治疗阿尔茨海默病进行了评估。通过聚变反应合成CGs是一种新的、简便的方法，具有产率高、反应时间短、化学物质少等优点，并使用HNMR对产物进行了表征。使用 Wistar 雄性大鼠进行不同的治疗。它们分为对照、假、阿尔茨海默、和测试组（阿尔茨海默氏症+α端基异构体和阿尔茨海默氏+β端基异构体）。动物分别接受生理盐水、东莨菪碱（1 mg/kg）、高剂量异头物、东莨菪碱和两剂异头物（12.5和25 mg/kg），持续10天。然后对所有动物进行莫里斯水迷宫（MWM）测试。最后，动物的大脑被提取并均质化，以检测
• Cannabinoid glycoside prodrugs and methods of synthesis
  申请人：Graphium Biosciences, Inc.

  公开号：US11207414B2

  公开（公告）日：2021-12-28

  The present invention relates to cannabinoid glycoside prodrugs suitable for site- and tissue-specific delivery of cannabinoid molecules. The present invention also relates to methods of forming the cannabinoid glycoside prodrugs through glycosyltransferase mediated glycosylation of cannabinoid molecules.

  本发明涉及适用于大麻素分子部位和组织特异性递送的大麻素苷原药。本发明还涉及通过糖基转移酶介导的大麻素分子糖基化形成大麻素苷原药的方法。
• Microbial transformation of curcumin by<i>Rhizopus chinensis</i>
  作者：Xing Zhang、Min Ye、Rui Li、Jun Yin、De-An Guo

  DOI：10.3109/10242422.2010.532870

  日期：2010.12

  Curcumin (1) is a potent antioxidant and antitumor natural product. In spite of its efficacy and safety, its clinical use is hindered mainly by poor water solubility and bioavailability. Structural modification to introduce hydrophilic functions is a promising approach to resolve this problem. In the present study we first found that curcumin could be efficiently converted into glucosides by filamentous fungi including Rhizopus chinensis IFFI 03043, Absidia coerulea AS 3.3389 and Cunninghamella elegans AS 3.1207. Curcumin 4'-O-beta-D-glucoside (2), together with hexahydrocurcumin (3), was isolated from a preparative-scale biotransformation with R. chinensis IFFI 03043 and characterized fully by NMR and MS. A time-course study revealed that curcumin could be efficiently converted into curcumin 4'-O-beta-D-glucoside within 8 h when administered at 0.05 mmol L-1 and the productivity was 57%. Additionally, the biotransformation products of curcumin by different fungal strains were analyzed by LC/MS. At least 15 metabolites were detected, and the predominant biotransformation reaction was glucosylation. This study provides a simple, efficient and less expensive approach for the preparation of curcumin glucosides. The introduction of the glucosyl function might be able to enhance the bioavailability of curcumin.
• CANNABINOID GLYCOSIDE PRODRUGS AND METHODS OF SYNTHESIS
  申请人：Graphium Biosciences, Inc.

  公开号：US20220168428A1

  公开（公告）日：2022-06-02

  The present invention relates to cannabinoid glycoside prodrugs suitable for site- and tissue-specific delivery of cannabinoid molecules. The present invention also relates to methods of forming the cannabinoid glycoside prodrugs through glycosyltransferase mediated glycosylation of cannabinoid molecules.