5-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]dihydro-2(3H)-furanone | 845673-64-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 内酯类
• 英文名称: 5-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]dihydro-2(3H)-furanone
• 英文别名: Dihydro-5-(3Z,6Z,9Z,12Z,15Z)-3,6,9,12,15-octadecapentaen-1-yl-2(3H)-furanone；5-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]oxolan-2-one
• CAS: 845673-64-5
• 化学式: C₂₂H₃₂O₂
• 分子量: 328.495
• InChiKey: OCCFPMRAUYUUSZ-JLNKQSITSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.1
• 重原子数：
  24
• 可旋转键数：
  12
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 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：

  5-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]dihydro-2(3H)-furanone 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 以82%的产率得到(7Z,10Z,13Z,16Z,19Z)-4-hydroxydocosa-7,10,13,16,19-pentaenoic acid
  参考文献：
  名称：

  Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents

  摘要：

  To discover novel peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that Could be used as antidiabetic agents, we designed docosahexacnoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPAR gamma. These compounds were synthesized via iodolactolic as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPAR gamma transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent Compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPAR gamma transcriptional activity, was separated as an optically pure form. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.074
• 作为产物：
  描述：

  5-((3Z,6Z,9Z,12Z,15Z)-1-iodooctadeca-3,6,9,12,15-pentaenyl)dihydro-2(3H)-furanone 在 三正丁基氢锡 作用下， 以 四氢呋喃 为溶剂， 反应 5.0h， 以66%的产率得到5-[(3Z,6Z,9Z,12Z,15Z)-octadeca-3,6,9,12,15-pentaenyl]dihydro-2(3H)-furanone
  参考文献：
  名称：

  Synthesis of docosahexaenoic acid derivatives designed as novel PPARγ agonists and antidiabetic agents

  摘要：

  To discover novel peroxisome proliferator-activated receptor gamma (PPAR gamma) agonists that Could be used as antidiabetic agents, we designed docosahexacnoic acid (DHA) derivatives (2 and 3), which have a hydrophilic substituent at the C(4)-position, based on the crystal structure of the ligand-binding pocket of PPAR gamma. These compounds were synthesized via iodolactolic as a key intermediate. We found that both DHA derivatives (2 and 3) showed PPAR gamma transactivation higher than, or comparable to, that of pioglitazone, which is a TZD derivative used as an antidiabetic agent. DHA derivatives related to these potent Compounds 2 and 3 were also synthesized to study structure-activity relationships. Furthermore, 4-OH DHA 2, which shows strong PPAR gamma transcriptional activity, was separated as an optically pure form. (c) 2005 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2005.07.074

文献信息

• Identification of putative metabolites of docosahexaenoic acid as potent PPARγ agonists and antidiabetic agents
  作者：Keiko Yamamoto、Toshimasa Itoh、Daijiro Abe、Masato Shimizu、Tomoatsu Kanda、Takatoshi Koyama、Masazumi Nishikawa、Tadakazu Tamai、Hiroshi Ooizumi、Sachiko Yamada

  DOI：10.1016/j.bmcl.2004.11.053

  日期：2005.2

  We found that putative metabolites of docosahexaenoic acid (DHA) are strong PPARgamma activators and potential antidiabetic agents. We designed DHA derivatives based on the crystal structure of PPARgamma, synthesized them and evaluated their activities in vitro and in vivo. The efficacy of 5E-4-hydroxy-DHA 2a as a PPARgamma activator was about fourfold stronger than that of pioglitazone. Further-more, the 4-keto derivative (10b) showed antidiabetic activity in animal models without producing undesirable effects such as obesity and hepatotoxicity. (C) 2004 Elsevier Ltd. All rights reserved.