2,3-epoxy-1-(3',4',5'-trimethoxyphenyl)-3-(4''-methoxyphenyl)propanone

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2,3-epoxy-1-(3',4',5'-trimethoxyphenyl)-3-(4''-methoxyphenyl)propanone
• 英文别名: (2RS,3SR)-2,3-epoxy-3-(4-methoxyphenyl)-1-(3,4,5-trimethoxyphenyl)propan-1-one；[(2S,3R)-3-(4-methoxyphenyl)oxiran-2-yl]-(3,4,5-trimethoxyphenyl)methanone
• 化学式: C₁₉H₂₀O₆
• 分子量: 344.364
• InChiKey: BFBOCNWCUSKNOS-IEBWSBKVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  66.5
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2,3-epoxy-1-(3',4',5'-trimethoxyphenyl)-3-(4''-methoxyphenyl)propanone 在 对甲苯磺酸 、 一水合肼 作用下， 以 xylene 为溶剂， 反应 3.0h， 以48%的产率得到3-(3,4,5-trimethoxyphenyl)-5-(4-methoxyphenyl)-1H-pyrazole
  参考文献：
  名称：

  Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins

  摘要：

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.028
• 作为产物：
  描述：

  3',4,4',5'-tetramethoxychalcone 在 双氧水 、 potassium carbonate 作用下， 以 甲醇 、 水 为溶剂， 反应 3.0h， 以54%的产率得到2,3-epoxy-1-(3',4',5'-trimethoxyphenyl)-3-(4''-methoxyphenyl)propanone
  参考文献：
  名称：

  Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins

  摘要：

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.06.028

文献信息

• A Novel One-Pot Rearrangement Reaction of 2,3-Epoxydiaryl Ketones: Synthesis of (±)-5,5-Disubstituted Imidazolones and 5,5-Disubstituted Hydantoins
  作者：Kanaya Dhar、Bilal Bhat、Satish Puri、Michael Spiteller

  DOI：10.1055/s-2006-950277

  日期：2006.10

  A novel one-pot rearrangement reaction, involving sequential epoxide rearrangement, condensation, cyclization and phenyl migration took place when 2,3-epoxydiphenyl ketones were treated with guanidine hydrochloride or urea in the presence of a base like sodium hydride and new type of imidazolone derivatives were obtained in good to excellent yields.

  在氢化钠等碱和新型咪唑酮衍生物存在下，用盐酸胍或尿素处理 2,3-环氧二苯基酮时，发生了一种新的一锅重排反应，包括顺序环氧化物重排、缩合、环化和苯基迁移以良好到极好的收率获得。
• Holt Jr., Herman; LeBlanc, Regan; Dickson, John, Heterocyclic Communications, 2005, vol. 11, # 6, p. 465 - 470
  作者：Holt Jr., Herman、LeBlanc, Regan、Dickson, John、Brown, Toni、Maddox, Jessica R.、Lee, Moses

  DOI：——

  日期：——
• Combretastatin-like chalcones as inhibitors of microtubule polymerization. Part 1: Synthesis and biological evaluation of antivascular activity
  作者：Sylvie Ducki、David Rennison、Meiko Woo、Alexander Kendall、Jérémie Fournier Dit Chabert、Alan T. McGown、Nicholas J. Lawrence

  DOI：10.1016/j.bmc.2009.09.039

  日期：2009.11

  The alpha-methyl chalcone SD400 is a potent inhibitor of tubulin assembly and possesses potent anticancer activity. Various chalcone analogues were synthesized and evaluated for their cell growth inhibitory properties against the K562 human chronic myelogenous leukemia cell line (SD400, IC50 0.21 nM; combretastatin A4 CA4, IC50 2.0 nM). Cell cycle analysis by flow cytometry indicated that these agents are antimitotic (SD400, 83% of the cells are in G(2)/M phase; CA4 90%). They inhibit tubulin assembly at low concentration (SD400, IC50 0.46 mu M; CA4, 0.10 mu M) and compete with [H-3] colchicine for binding to tubulin (8% [H-3] colchicine remained bound to tubulin after competition with SD400 or CA4). Upon treatment with SD400, remarkable cell shape changes were elicited in HUVEC cells, consistent with vasculature damaging activity. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis and cytotoxicity of epoxide and pyrazole analogs of the combretastatins
  作者：Regan LeBlanc、John Dickson、Toni Brown、Michelle Stewart、Hari N. Pati、Don VanDerveer、Hadi Arman、Jeff Harris、William Pennington、Herman L. Holt、Moses Lee

  DOI：10.1016/j.bmc.2005.06.028

  日期：2005.11

  Twenty-six epoxide and corresponding pyrazole derivatives, of the structurally related chalcones and combretastatin A-4 (CA-4), were synthesized and tested for in vitro cytotoxicity. These molecules were synthesized by epoxidation of the relevant chalcones, followed by reaction with hydrazine. The structures of epoxides 3 and 7, and pyrazole 17, were confirmed by X-ray diffraction studies. The relatively coplanar conformation of a 3',3",4',4",5',5"-hexamethoxypyrazole 17 was in good agreement with the shape for 3',3",4',4",5'-pentamethoxypyrazole 16, which was determined from molecular mechanics optimization. In vitro cytotoxicity of each class of compounds was obtained using a 72 h continuous exposure MTT assay against two murine cancer cell lines; B16 melanoma and L1210 leukemia. The effect of substitution in the A-ring is addressed: three methoxy groups versus two, generally increased cytotoxicity across both cell lines. In the majority of cases, the pyrazoles are generally more active than the epoxides, with the most active, 5-(3"-amino-4"-methoxyphenyl)-3-(3',4',5'-trimethoxyphenyl)pyrazole 21, possessing an IC50 value of 5 and 2.4 mu M (B16 and L1210, respectively). Due to their planar conformations, the pyrazoles are typically less active than the corresponding chalcones, which adopt angular conformations similar to CA-4. B-ring modifications confirmed that in general the amino compounds are more active than the corresponding nitro compounds. Varying the number and orientation of methoxy groups on the A-ring did not produce any significant differences in toxicity in the cell lines studied. (c) 2005 Elsevier Ltd. All rights reserved.