(E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3,4-dimethoxyphenyl)but-3-en-2-one | 1042966-21-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 肉桂酸及其衍生物
• 英文名称: (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3,4-dimethoxyphenyl)but-3-en-2-one
• 英文别名: [(2R,3R,4R,5S,6S)-3,4,5-triacetyloxy-6-[(E)-4-(3,4-dimethoxyphenyl)-2-oxobut-3-enyl]oxan-2-yl]methyl acetate
• CAS: 1042966-21-1
• 化学式: C₂₆H₃₂O₁₂
• 分子量: 536.533
• InChiKey: CQWULWJFLMNGEK-CVEQTENHSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.4
• 重原子数：
  38
• 可旋转键数：
  15
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  150
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3,4-dimethoxyphenyl)but-3-en-2-one 在 甲醇 、 sodium methylate 作用下， 反应 0.17h， 以95%的产率得到1-(β-D-glucopyranosyl)-4-(3,4-dimethoxyphenyl)but-3-en-2-one
  参考文献：
  名称：

  以α,β-不饱和酮为先导结构的羟基化联苯衍生物的合成，用于开发针对恶性黑色素瘤的候选药物

  摘要：

  制备了一小部分以 α,β-不饱和酮为先导结构的 C 2对称羟基化联苯衍生物，并测定了这些化合物作为抗增殖剂对抗四种人类恶性黑色素瘤细胞系的能力。应用前药方法是为了通过调节酚羟基保护基团来改善化合物向细胞的递送。发现带有α,β-不饱和酮和酚-O-异戊二烯化链的羟基化联苯结构有助于分子的传递和与生物靶标的相互作用。四种化合物显示出抗增殖活性，导致 IC 50值在 1.2 至 2.8 μM 的范围内。

  DOI：

  10.1002/cmdc.202000709
• 作为产物：
  描述：

  可得然胶 在 四氢吡咯 、 吡啶 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 为溶剂， 反应 23.0h， 生成 (E)-1-(2',3',4',6'-tetra-O-acetyl-β-D-glucopyranosyl)-4-(3,4-dimethoxyphenyl)but-3-en-2-one
  参考文献：
  名称：

  Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII

  摘要：

  The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.

  DOI：

  10.1016/j.bmc.2014.07.052

文献信息

• Synthesis of C -glycosylmethyl isoxazoles via aerobic oxidation of ketoximes catalyzed by TEMPO
  作者：Helberth Llantén、Sebastian Barata-Vallejo、Al Postigo、Pedro A. Colinas

  DOI：10.1016/j.tetlet.2017.03.005

  日期：2017.4

  An efficient and high yielding synthesis of C-glycosylmethyl isoxazoles by oxidation of ketoximes in the presence of oxygen and mediated by TEMPO is described. (C) 2017 Elsevier Ltd. All rights reserved.
• Aldol reaction of β-C-glycosylic ketones: synthesis of C-(E)-cinnamoyl glycosylic compounds as precursors for new biologically active C-glycosides
  作者：Surendra Singh Bisht、Jyoti Pandey、Anindra Sharma、Rama Pati Tripathi

  DOI：10.1016/j.carres.2008.04.021

  日期：2008.7

  A series of beta-C-glycosylic ketones were prepared starting from D-glucose, D-xylose, D-mannose, and cellobiose. The beta-C-glycosylic ketones on aldol condensation with different aromatic aldehydes in the presence of a suitable organocatalyst led to the formation of respective C-(E)-cinnamoyl glycosides stereoselectively in good yields as precursors for the synthesis of biologically active compounds. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthetic studies in butenonyl C-glycosides: Preparation of polyfunctional alkanonyl glycosides and their enzyme inhibitory activity
  作者：Surendra Singh Bisht、Seerat Fatima、Akhilesh K. Tamrakar、Neha Rahuja、Natasha Jaiswal、Arvind K. Srivastava、Rama P. Tripathi

  DOI：10.1016/j.bmcl.2009.03.136

  日期：2009.5

  A simple synthesis of phenyl butenoyl C-glycosides has been achieved by Aldol condensation of peracetylated glycosyl acetones with aromatic aldehydes followed by deacetylation with methanolic NaOMe. The selected butenoyl C-glycosides on conjugate addition of diethyl malonate resulted in polyfunctional alkanonyl glycosides in good yields. The butenoyl C- and alkanoyl C- glycosides were evaluated for their alpha-glucosidase, glucose-6-phosphatse and glycogen phosphorylase enzyme inhibitory activities in vitro. Three of the synthesized (3, 5 and 9) showed potent enzyme inhibitory activities as compared to standard drugs. Compounds 3, 5 and 9 were evaluated in vivo too displaying significant activity as compared to standard drugs acarbose and metformin. (C) 2009 Elsevier Ltd. All rights reserved.
• Attachment of carbohydrates to methoxyaryl moieties leads to highly selective inhibitors of the cancer associated carbonic anhydrase isoforms IX and XII
  作者：Leonardo E. Riafrecha、Oscar M. Rodríguez、Daniela Vullo、Claudiu T. Supuran、Pedro A. Colinas

  DOI：10.1016/j.bmc.2014.07.052

  日期：2014.10

  The transmembrane isoforms of carbonic anhydrase (hCA IX and XII) have been shown to be linked to carcinogenesis and their inhibition to arrest primary tumor and metastases growth. In this paper, we present a new class of C-glycosides incorporating the methoxyaryl moiety, that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. The glycosides have been prepared by aldol reaction of glycosyl ketones with the appropriate aromatic aldehydes. We also present the inhibition profile of our new glycomimetics, against four isozymes of carbonic anhydrase comprising hCAs I and II (cytosolic, ubiquitous isozymes) and hCAs IX and XII (tumor associated isozymes). In this study, per-O-acetylated glycoside 4, 6 and deprotected compounds 7, 9, 10 and 12 were identified as potent and highly selective inhibitors of hCA IX and XII. These results confirm that attaching carbohydrate moieties to CA methoxyaryl pharmacophore improves and enhances its inhibitory activity. These CA inhibitors have developmental potential to selectively target cancer cells, leading to cell death.
• Synthesis of Hydroxylated Biphenyl Derivatives Bearing an α,β‐Unsaturated Ketone as a Lead Structure for the Development of Drug Candidates against Malignant Melanoma
  作者：Maria Antonietta Dettori、Marina Pisano、Carla Rozzo、Giovanna Delogu、Davide Fabbri

  DOI：10.1002/cmdc.202000709

  日期：2021.3.18

  A small collection of C2‐symmetric hydroxylated biphenyl derivatives featuring an α,β‐unsaturated ketone as a lead structure was prepared, and the capacity of these compounds to act as antiproliferative agents against four human malignant melanoma cell lines was assayed. The prodrug approach was applied in order to improve the delivery of compounds into the cell by modulation of the phenolic hydroxy

  制备了一小部分以 α,β-不饱和酮为先导结构的 C 2对称羟基化联苯衍生物，并测定了这些化合物作为抗增殖剂对抗四种人类恶性黑色素瘤细胞系的能力。应用前药方法是为了通过调节酚羟基保护基团来改善化合物向细胞的递送。发现带有α,β-不饱和酮和酚-O-异戊二烯化链的羟基化联苯结构有助于分子的传递和与生物靶标的相互作用。四种化合物显示出抗增殖活性，导致 IC 50值在 1.2 至 2.8 μM 的范围内。