(+/-)-(E)-1-(dimethoxyphosphoryl)pentadec-2-en-1-yl methyl carbonate | 1412440-00-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: (+/-)-(E)-1-(dimethoxyphosphoryl)pentadec-2-en-1-yl methyl carbonate
• 英文别名: [(E)-1-dimethoxyphosphorylpentadec-2-enyl] methyl carbonate
• CAS: 1412440-00-6
• 化学式: C₁₉H₃₇O₆P
• 分子量: 392.473
• InChiKey: WLPXUUHKKVPOAU-WUKNDPDISA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.6
• 重原子数：
  26
• 可旋转键数：
  18
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.84
• 拓扑面积：
  71.1
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-十四烯 、 dimethyl [1-(methoxycarbonyloxy)-2-propenyl] phosphonate 在 RuCl2(1,3-dimesityl-imidazolidin-2-yl)(PCy3)(=CHPh) 、 copper(l) iodide 作用下， 以 二氯甲烷 为溶剂， 以77.778%的产率得到
  参考文献：
  名称：

  Synthesis and Kinetic Evaluation of Cyclophostin and Cyclipostins Phosphonate Analogs As Selective and Potent Inhibitors of Microbial Lipases

  摘要：

  A new series-of customizable diastereomeric cis- and trans-monocyclic enol-phosphonate analogs to Cyclophostin and Cyclipostins were synthesized. Their potencies and mechanisms of inhibition. toward six representative lipolytic enzymes belonging to distinct lipase families Were examined. With Mammalian gastric and pancreatic lipases no inhibition occurred with any of the compounds tested. Conversely, Fusarium solani Cutinase and. lipases from, Mycobacterium tuberculosis (Rv0183 and LipY) were all fully. inactivated. The best inhibitors displayed a cis conformation (H and OMe) and exhibited higher inhibitory activities than the lipase inhibitor Orlistat toward the same enzymes. Our results have revealed that chemical group at the gamma-carbon the phosphonate ring strongly impacts the inhibitory efficiency, leading to a significant improvement in selectivity toward a target lipase over another. The powerful and selective inhibition of microbial (fungal and mycobacterial) lipases suggests that these seven-membered monocyclic enol-phosphonates should provide useful leads for the development of novel and highly selective antimicrobial agents.

  DOI：

  10.1021/jm301216x

文献信息

• Synthesis and Kinetic Evaluation of Cyclophostin and Cyclipostins Phosphonate Analogs As Selective and Potent Inhibitors of Microbial Lipases
  作者：Vanessa Point、Raj K. Malla、Sadia Diomande、Benjamin P. Martin、Vincent Delorme、Frederic Carriere、Stephane Canaan、Nigam P. Rath、Christopher D. Spilling、Jean−François Cavalier

  DOI：10.1021/jm301216x

  日期：2012.11.26

  A new series-of customizable diastereomeric cis- and trans-monocyclic enol-phosphonate analogs to Cyclophostin and Cyclipostins were synthesized. Their potencies and mechanisms of inhibition. toward six representative lipolytic enzymes belonging to distinct lipase families Were examined. With Mammalian gastric and pancreatic lipases no inhibition occurred with any of the compounds tested. Conversely, Fusarium solani Cutinase and. lipases from, Mycobacterium tuberculosis (Rv0183 and LipY) were all fully. inactivated. The best inhibitors displayed a cis conformation (H and OMe) and exhibited higher inhibitory activities than the lipase inhibitor Orlistat toward the same enzymes. Our results have revealed that chemical group at the gamma-carbon the phosphonate ring strongly impacts the inhibitory efficiency, leading to a significant improvement in selectivity toward a target lipase over another. The powerful and selective inhibition of microbial (fungal and mycobacterial) lipases suggests that these seven-membered monocyclic enol-phosphonates should provide useful leads for the development of novel and highly selective antimicrobial agents.