[(E)-1-[dimethoxy(oxido)phosphaniumyl]oct-2-enyl] methyl carbonate | 1172594-93-2

• 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-[dimethoxy(oxido)phosphaniumyl]oct-2-enyl] methyl carbonate
• CAS: 1172594-93-2
• 化学式: C₁₂H₂₃O₆P
• 分子量: 294.285
• InChiKey: HKMWQKKKEYTMAU-MDZDMXLPSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  19
• 可旋转键数：
  11
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.75
• 拓扑面积：
  77
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  [(E)-1-[dimethoxy(oxido)phosphaniumyl]oct-2-enyl] methyl carbonate 在 tris-(dibenzylideneacetone)dipalladium(0) 、 palladium 10% on activated carbon 、 氢气 、 1,2-双(二苯基膦)乙烷 、 sodium iodide 作用下， 以 四氢呋喃 、 甲醇 、 乙腈 为溶剂， 反应 17.5h， 生成 Methoxy-[3-(1-methoxy-1,3-dioxobutan-2-yl)octyl]phosphinic acid
  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 of Cyclopentenones via Intramolecular HWE and the Palladium-Catalyzed Reactions of Allylic Hydroxy Phosphonate Derivatives
  作者：Bingli Yan、Christopher D. Spilling

  DOI：10.1021/jo8004028

  日期：2008.7.1

  Palladium-catalyzed decarboxylative rearrangement of nonracemic phosphono allylic acetoacetates, or the intermolecular allylic substitution of nonracemic phosphono allylic carbonates with tert-butyl acetoacetate followed by hydrolysis and decarboxylation, gave ω-ketovinyl phosphonates. A highly regioselective Wacker oxidation gave the ω,β-diketophosphonates which underwent intramolecular HWE reaction

  非外消旋膦酰基烯丙基乙酰乙酸的钯催化脱羧重排，或非乙酸膦酰基烯丙基碳酸酯的分子间烯丙基取代为乙酰乙酸叔丁酯，随后水解和脱羧，得到ω-酮乙烯基膦酸酯。高度区域选择性的Wacker氧化产生了ω，β-二酮膦酸酯，使其经历分子内HWE反应以生成非外消旋的环戊烯酮。导致膦酰基环戊烯酮的醛醇缩合与HWE反应竞争。环戊烯酮的立体化学和HWE与醛醇产物的比例取决于反应中所用碱的选择。
• Stereoselective Synthesis of Cyclic Ethers via the Palladium-Catalyzed Intramolecular Addition of Alcohols to Phosphono Allylic Carbonates
  作者：Anyu He、Nongnuch Sutivisedsak、Christopher D. Spilling

  DOI：10.1021/ol900980s

  日期：2009.7.16

  Cross metathesis of the acrolein-derived phosphono allylic carbonate and hydroxy alkenes using second generation Grubbs catalyst and copper(I) iodide gave the substituted phosphonates in good yield. Stereospecific palladium(0)-catalyzed cyclization gave tetrahydrofuran and tetrahydropyran vinyl phosphonates. Regioselective Wacker oxidation of the vinyl phosphonate gave the β-keto phosphonate, which

  使用第二代格鲁布斯催化剂和碘化铜(I)对丙烯醛衍生的膦酰基烯丙碳酸酯和羟基烯烃进行交叉复分解，以良好的收率得到取代的膦酸酯。立体定向钯(0) 催化环化得到四氢呋喃和四氢吡喃乙烯基膦酸酯。乙烯基膦酸酯的区域选择性瓦克氧化得到 β-酮基膦酸酯，其与苯甲醛进行 HWE 反应，生成不饱和酮。 centrolobine 的正式合成进一步证明了交叉复分解/环化方案的实用性。
• 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.