Dehydroascofuranone

• 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: Dehydroascofuranone
• 英文别名: 3-chloro-5-<(E,E)-7-(4,5-dihydro-5,5-dimethyl-4-oxofuran-2-yl)-3-methylocta-2,6-dienyl>-4,6-dihydroxy-2-methylbenzaldehyde；5-chloro-3-[(2E,6E)-7-(5,5-dimethyl-4-oxofuran-2-yl)-3-methylocta-2,6-dienyl]-2,4-dihydroxy-6-methylbenzaldehyde
• 化学式: C₂₃H₂₇ClO₅
• 分子量: 418.917
• InChiKey: NBIWEELILKYZAL-UAUIHIKDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  83.8
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  5-氯-3-[(2E,6E)-7-[(2S)-5,5-二甲基-4-氧代四氢呋喃-2-基]-3-甲基辛-2,6-二烯基]-2,4-二羟基-6-甲基苯甲醛 在 sodium hydroxide 、 silver nitrate 作用下， 以 1,4-二氧六环 为溶剂， 反应 3.0h， 以24%的产率得到Dehydroascofuranone
  参考文献：
  名称：

  Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors

  摘要：

  Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylasco(hlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3HIOT1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-0-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.

  DOI：

  10.1021/jm0205649

文献信息

• Total Synthesis of<i>dl</i>-Ascofuranone and Related Compounds
  作者：Hiroyuki Saimoto、Shin-ichiro Ohrai、Hitoshi Sashiwa、Yoshihiro Shigemasa、Tamejiro Hiyama

  DOI：10.1246/bcsj.68.2727

  日期：1995.9

  Convergent synthesis of an antitumor protective agent, ascofuranone, was accomplished by (1) preparation of the terpenoid side chain having a furanone moiety, (2) coupling the side chain with a protected phenol derivative, and (3) deprotection to regenerate the hydroxyl groups. This strategy was successfully applied to the synthesis of oxidized and cyclized analogs of ascofuranone. Some of the ascofuranone

  通过 (1) 制备具有呋喃酮部分的萜类侧链，(2) 将侧链与受保护的苯酚衍生物偶联，以及 (3) 脱保护以再生羟基，从而实现了抗肿瘤保护剂 ascofuranone 的聚合合成. 该策略已成功应用于合成呋喃酮的氧化和环化类似物。发现一些呋喃酮衍生物可抑制 P388 白血病细胞的生长。
• EP1481670
  申请人：——

  公开号：——

  公开（公告）日：——
• EP1176134
  申请人：——

  公开号：——

  公开（公告）日：——
• Ascochlorin Derivatives as Ligands for Nuclear Hormone Receptors
  作者：Marie Togashi、Satoshi Ozawa、Shoko Abe、Tomoyuki Nishimura、Mie Tsuruga、Kunio Ando、Gakuzo Tamura、Shigefumi Kuwahara、Makoto Ubukata、Junji Magae

  DOI：10.1021/jm0205649

  日期：2003.9.1

  Nuclear receptor family proteins are structurally related transcription factors activated by specific lipophilic compounds. Because they are activated by a variety of hormonal molecules, including retinoic acid, vitamin D, and steroid hormones, they are assumed to be promising targets for clinical drugs. We previously found that one ascochlorin (1) derivative, 4-O-carboxymethyl-ascochlorin (2), is a potent agonist of peroxisome proliferator activated receptor gamma (PPARgamma). Here, we synthesized derivatives of 1, designated as a lead compound, to create new modulators of nuclear hormone receptors. Two derivatives, 4-O-carboxymethyl-2-O-methylascochlorin (9) and 4-O-isonicotinoyl-2-O-methylasco(hlorin (10), showed improved agonistic activity for PPARgamma and induced differentiation of a progenitor cell line, C3HIOT1/2. We also found that 1, dehydroascofuranon (29), and a 2,4-0-diacetyl-1-carboxylic acid derivative of 1 (5) specifically activated estrogen receptors, PPARalpha, and an androgen receptor. All of the derivatives (1-29) activated the pregnane X receptor. These results suggest that the chemical structure of 1 is useful in designing novel modulators of nuclear receptors.