(1E,3E)-1-(3-guaiazulenyl)-4-[4-(methoxycarbonyl)phenyl]-1,3-butadiene | 152531-75-4

• 分子结构分类: 有机化合物 - 脂质和类脂质分子 - 异戊烯醇脂质
• 英文名称: (1E,3E)-1-(3-guaiazulenyl)-4-[4-(methoxycarbonyl)phenyl]-1,3-butadiene
• 英文别名: methyl 4-[(1E,3E)-4-(3,8-dimethyl-5-propan-2-ylazulen-1-yl)buta-1,3-dienyl]benzoate
• CAS: 152531-75-4
• 化学式: C₂₇H₂₈O₂
• 分子量: 384.518
• InChiKey: YYFAUKHYFLVCSQ-CDJQDVQCSA-N

物化性质

• 熔点：
  121 °C(Solvent: Methanol; Chloroform)
• 沸点：
  567.6±39.0 °C(predicted)
• 密度：
  1.086±0.06 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  7.5
• 重原子数：
  29
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.22
• 拓扑面积：
  26.3
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (1E,3E)-1-(3-guaiazulenyl)-4-[4-(methoxycarbonyl)phenyl]-1,3-butadiene 在 氢氧化钾 作用下， 以 四氢呋喃 、 甲醇 、 水 为溶剂， 反应 0.5h， 以94%的产率得到4-<4-<1-<3,8-dimethyl-5-(1-methylethyl)azulenyl>>-1,3-butadienyl>benzoic acid
  参考文献：
  名称：

  Azulenic retinoids: novel nonbenzenoid aromatic retinoids with anticancer activity

  摘要：

  Several novel azulene-containing retinoids were prepared and evaluated for their ability to suppress carcinogen-induced neoplastic transformation and to concomitantly up-regulate gap junctional communication in the in vitro mouse fibroblast C3H/10T1/2 cell bioassay. The azulenic retinoids were divided into two groups: compounds 1-6 were modeled after retinoic acid with flexible polyenic side chain whereas retinoids 7-13 featured a benzoic acid moiety analogous to the prototypic retinobenzoate (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB). Within this latter group the side chains for compounds 7, 10, and 11 were attached at the 1-, 2-, and 8-positions of the azulenic terminus, respectively. Biological activities were determined for all the new compounds. Two of these novel retinoids, azulenic retinobenzoic acid derivatives 7 and 11, were completely effective inhibitors of transformation at 10(-6) M. The most active azulenic retinoids also enhanced gap junctional communication in untransformed cells; this was associated with up-regulated expression of connexin 43, a structural protein of the gap junction. Two fluorinated analogs were also tested. The azulenic fluoro acid 5 was found to be more potent than the trifluoromethyl analog 6. Azulenic analogs with hydroxyl or carboxaldehyde side chain functional groups were ineffective transformation inhibitors. In general, azulenic retinobenzoic acid analogs structurally akin to TTNPB were more effective than flexible side chain analogs related to retinoic acid.

  DOI：

  10.1021/jm00073a013
• 作为产物：
  描述：

  3-<1-<3,8-dimethyl-5-(1-methylethyl)azulenyl>>-2-propenenitrile 在 sodium hydride 、 二异丁基氢化铝 作用下， 以 乙醚 、 二氯甲烷 、 正戊烷 为溶剂， 反应 2.0h， 生成 (1E,3E)-1-(3-guaiazulenyl)-4-[4-(methoxycarbonyl)phenyl]-1,3-butadiene
  参考文献：
  名称：

  Azulenic retinoids: novel nonbenzenoid aromatic retinoids with anticancer activity

  摘要：

  Several novel azulene-containing retinoids were prepared and evaluated for their ability to suppress carcinogen-induced neoplastic transformation and to concomitantly up-regulate gap junctional communication in the in vitro mouse fibroblast C3H/10T1/2 cell bioassay. The azulenic retinoids were divided into two groups: compounds 1-6 were modeled after retinoic acid with flexible polyenic side chain whereas retinoids 7-13 featured a benzoic acid moiety analogous to the prototypic retinobenzoate (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB). Within this latter group the side chains for compounds 7, 10, and 11 were attached at the 1-, 2-, and 8-positions of the azulenic terminus, respectively. Biological activities were determined for all the new compounds. Two of these novel retinoids, azulenic retinobenzoic acid derivatives 7 and 11, were completely effective inhibitors of transformation at 10(-6) M. The most active azulenic retinoids also enhanced gap junctional communication in untransformed cells; this was associated with up-regulated expression of connexin 43, a structural protein of the gap junction. Two fluorinated analogs were also tested. The azulenic fluoro acid 5 was found to be more potent than the trifluoromethyl analog 6. Azulenic analogs with hydroxyl or carboxaldehyde side chain functional groups were ineffective transformation inhibitors. In general, azulenic retinobenzoic acid analogs structurally akin to TTNPB were more effective than flexible side chain analogs related to retinoic acid.

  DOI：

  10.1021/jm00073a013

文献信息

• Preparation, Crystal Structures, and Spectroscopic and Chemical Properties of 2,4,6-Trifluorophenyl- or 4-(Methoxycarbonyl)phenyl-Substituted (<i>E</i>)-1-(3-Guaiazulenyl)ethylene and (2<i>E</i>,4<i>E</i>)-1-(3-Guaiazulenyl)-1,3-butadiene Derivatives
  作者：Shin-ichi Takekuma、Hiroto Matsuoka、Syoutarou Ogawa、Yasutaka Shibasaki、Toshie Minematsu

  DOI：10.1246/bcsj.20100069

  日期：2010.10.15

  Wittig reactions in general provide a mixture of E and Z geometric isomers, while reactions of 2,4,6-trifluorobenzaldehyde [and (E)-3-(2,4,6-trifluorophenyl)propanal] with the Wittig reagent (3-guaiazulenyl)triphenylphosphonium bromide in ethanol containing NaOEt at 25 °C for 24 h under argon give only new E (and 2E,4E)-forms selectively, i.e., (E)-1-(3-guaiazulenyl)-2-(2,4,6-trifluorophenyl)ethylene and (2E,4E)-1-(3-guaiazulenyl)-4-(2,4,6-trifluorophenyl)-1,3-butadiene. For comparative purposes, Wittig reactions of methyl 4-formylbenzoate, 4-(dimethylamino)benzaldehyde, methyl 4-[(E)-2-formylethenyl]benzoate, and (E)-3-[4-(dimethylamino)phenyl]propanal: namely, possessing an electron-withdrawing (–COOCH3) or an electron-donating [–N(CH3)2]} group at the C-4 position of the benzene ring, with (3-guaiazulenyl)triphenylphosphonium bromide in methanol (or ethanol) containing NaOMe (or NaOEt) at 25 °C for 24 h under argon afford a mixture of the corresponding geometric isomers respectively. Along with spectroscopic properties and crystal structures of the isolated products, the chemical behavior of those products toward 1,1,2,2-tetracyanoethylene (TCNE) in benzene at 25 °C for 24 h under argon is reported with a view to comparative study.

  维蒂希反应通常提供 E 和 Z 几何异构体的混合物，而 2,4,6-三氟苯甲醛 [和 (E)-3-(2,4,6-三氟苯基)丙醛] 与维蒂希试剂的反应 (3-愈创木薁基）三苯基溴化鏻在含有NaOEt的乙醇中于25℃在氩气下反应24小时仅选择性地产生新的E（和2E,4E）-形式，即（E）-1-（3-愈创木薁基）-2-（2， 4,6-三氟苯基)乙烯和(2E,4E)-1-(3-愈创蓝基)-4-(2,4,6-三氟苯基)-1,3-丁二烯。为了比较，4-甲酰基苯甲酸甲酯、4-(二甲氨基)苯甲醛、4-[(E)-2-甲酰基乙烯基]苯甲酸甲酯和(E)-3-[4-(二甲氨基)苯基]丙醛的维蒂希反应：即在苯环的C-4位上具有吸电子(-COOCH3)或给电子基团[-N(CH3)2]}，与(3-愈创蓝基)三苯基溴化鏻在甲醇(或含有NaOMe（或NaOEt）的乙醇）在25℃、氩气下反应24小时，分别得到相应几何异构体的混合物。除了分离产物的光谱性质和晶体结构外，还报告了这些产物在氩气下于 25 °C 下在苯中 24 小时对 1,1,2,2-四氰乙烯 (TCNE) 的化学行为，以进行比较研究。
• Azulenic retinoids: novel nonbenzenoid aromatic retinoids with anticancer activity
  作者：Alfred E. Asato、Ao Peng、Mohammad Z. Hossain、Taraneh Mirzadegan、John S. Bertram

  DOI：10.1021/jm00073a013

  日期：1993.10

  Several novel azulene-containing retinoids were prepared and evaluated for their ability to suppress carcinogen-induced neoplastic transformation and to concomitantly up-regulate gap junctional communication in the in vitro mouse fibroblast C3H/10T1/2 cell bioassay. The azulenic retinoids were divided into two groups: compounds 1-6 were modeled after retinoic acid with flexible polyenic side chain whereas retinoids 7-13 featured a benzoic acid moiety analogous to the prototypic retinobenzoate (E)-4-[2-(5,6,7,8-tetrahydro-5,5,8,8-tetramethyl-2-naphthalenyl)-1-propenyl]benzoic acid (TTNPB). Within this latter group the side chains for compounds 7, 10, and 11 were attached at the 1-, 2-, and 8-positions of the azulenic terminus, respectively. Biological activities were determined for all the new compounds. Two of these novel retinoids, azulenic retinobenzoic acid derivatives 7 and 11, were completely effective inhibitors of transformation at 10(-6) M. The most active azulenic retinoids also enhanced gap junctional communication in untransformed cells; this was associated with up-regulated expression of connexin 43, a structural protein of the gap junction. Two fluorinated analogs were also tested. The azulenic fluoro acid 5 was found to be more potent than the trifluoromethyl analog 6. Azulenic analogs with hydroxyl or carboxaldehyde side chain functional groups were ineffective transformation inhibitors. In general, azulenic retinobenzoic acid analogs structurally akin to TTNPB were more effective than flexible side chain analogs related to retinoic acid.