dimethyl (2-oxo-2-(1H-pyrrol-1-yl)ethyl)phosphonate | 1346683-43-9

• 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: dimethyl (2-oxo-2-(1H-pyrrol-1-yl)ethyl)phosphonate
• 英文别名: 2-Dimethoxyphosphoryl-1-pyrrol-1-ylethanone；2-dimethoxyphosphoryl-1-pyrrol-1-ylethanone
• CAS: 1346683-43-9
• 化学式: C₈H₁₂NO₄P
• 分子量: 217.161
• InChiKey: MTYJLHAJSZQJGN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.2
• 重原子数：
  14
• 可旋转键数：
  4
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  57.5
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  dimethyl (2-oxo-2-(1H-pyrrol-1-yl)ethyl)phosphonate 在 allyl(cyclopentadiene)palladium(II) 、 C₄₁H₅₀N₄O₂P₂ 、 N,N-二异丙基乙胺 、 lithium chloride 作用下， 以 1,4-二氧六环 、 乙腈 为溶剂， 反应 30.41h， 生成 ((1S,2S,3R)-4-methylene-2-(4-(trimethylsilyl)but-3-yn-1-yl)-3-((trimethylsilyl)ethynyl)cyclopentyl)(1H-pyrrol-1-yl)methanone
  参考文献：
  名称：

  快速增加分子复杂性的方法：融合多环系统的原子经济路线。

  摘要：

  已经开发了使用手性双二氨基亚磷酸酯配体的炔基取代的TMM供体和不饱和N-酰基吡咯的不对称三亚甲基甲烷（TMM）[3 + 2]环加成反应的方案。该方法以高收率和非对映和对映选择性产生炔基取代的环戊烷。这些手性前体用于通过连续的环加成反应将稠合的多环烃与氢茚，氢腈和氢环戊萘支架进行原子经济组装。

  DOI：

  10.1021/ol5009872
• 作为产物：
  描述：

  二-1H-吡咯-1-基甲酮 、 甲基膦酸二甲酯 在 正丁基锂 作用下， 以 四氢呋喃 、 正己烷 为溶剂， 反应 4.0h， 以82%的产率得到dimethyl (2-oxo-2-(1H-pyrrol-1-yl)ethyl)phosphonate
  参考文献：
  名称：

  使用1,6-受体扩展Stetter反应

  摘要：

  Pace Stetter：描述了一种新的N杂环卡宾（NHC）催化的转化-分子内乙烯基Stetter反应。可以使用噻唑鎓和三唑鎓类催化剂，使用芳族和脂族醛，使用α，β，γ，δ-不饱和酯，酮，膦酸酯和N-酰基吡咯进行这种转化，并且可以对映选择性地进行（参见方案）。

  DOI：

  10.1002/chem.201303435

文献信息

• Enantioselective Construction of Highly Substituted Vinylidenecylopentanes by Palladium-Catalyzed Asymmetric [3+2] Cycloaddition Reaction
  作者：Barry M. Trost、Autumn Maruniak

  DOI：10.1002/anie.201300275

  日期：2013.6.10

  A new cycloadduct: The title reaction of methylene‐trimethylenemethane (TMM) with α,β‐unsaturated N‐acyl pyrroles is an efficient method for the construction of vinylidenecyclopentanes. An asymmetric protocol using this unique donor forms cycloadducts in excellent yield and enantioselectivity, making use of a bisdiamidophosphite ligand derived from trans‐1,2‐stilbenediamine.

  一种新的环加合物：亚甲基三亚甲基甲烷（TMM）与α，β-不饱和N-酰基吡咯的标题反应是构建亚乙烯基亚环戊烷的有效方法。使用这种独特的供体的不对称方案利用衍生自反式1,2-二苯乙烯二胺的双二亚氨基亚磷酸酯配体，以优异的收率和对映选择性形成环加合物。
• Anion-Stoichiometry-Dependent Selectivity Enhancement in Ion-Paired Chiral Ligand–Palladium Complex Catalyzed Enantioselective Allylic Alkylation
  作者：Takashi Ooi、Kohsuke Ohmatsu、Yoshiyuki Hara、Yuya Kusano

  DOI：10.1055/s-0035-1561403

  日期：——

  The ratio of chiral Bronsted acid to ammonium–phosphine hybrid ligand in the in situ preparation of ion-paired chiral ligands was found to have a notable effect on the stereocontrolling ability of the corresponding palladium complex. The use of supramolecular palladium complexes generated from palladium metal, ammonium phosphine, and a chiral phosphoric acid in a ratio of 1:2:3 enabled an excellent

  发现在离子对手性配体的原位制备中手性布朗斯台德酸与铵-膦杂化配体的比例对相应钯配合物的立体控制能力有显着影响。使用由钯金属、铵膦和手性磷酸以 1:2:3 的比例生成的超分子钯配合物能够在 α-硝基羧酸酯与官能化烯丙基碳酸酯的催化不对称烯丙基化反应中实现出色的对映控制水平。
• A New Class of Highly Potent and Selective Endomorphin-1 Analogues Containing α-Methylene-β-aminopropanoic Acids (Map)
  作者：Yuan Wang、Yanhong Xing、Xin Liu、Hong Ji、Ming Kai、Zongyao Chen、Jing Yu、Depeng Zhao、Hui Ren、Rui Wang

  DOI：10.1021/jm300664y

  日期：2012.7.12

  A new class of endomorphin-1 (EM-1) analogues were synthesized by introduction of novel unnatural alpha-methylene-beta-amino acids (Map) at position 3 or/and position 4. Their binding and functional activity, metabolic stability, and antinociceptive activity were determined and compared. Most of these analogues showed high affinities for the mu-opioid receptor and an increased stability in mouse brain homogenates compared with EM-1. Examination of cAMP accumulation and ERK1/2 phosphorylation in HEK293 cells confirmed the agonist properties of these analogues. Among these new analogues, H-Tyr-Pro-Trp-(2-furyl)Map-NH2 (analogue 12) exhibited the highest binding potency (K-i(mu) = 0.221 nM) and efficacy (EC50 = 0.0334 nM, E-max = 97.14%). This analogue also displayed enhanced antinociceptive activity in vivo in comparison to EM-1. Molecular modeling approaches were then carried out to demonstrate the interaction pattern of these analogues with the opioid receptors. We found that, compared to EM-1, the incorporation of our synthesized Map at position 4 would bring the analogue to a closer binding mode with the mu-opioid receptor.
• Design, Synthesis, and Pharmacological Characterization of Novel Endomorphin-1 Analogues as Extremely Potent μ-Opioid Agonists
  作者：Xin Liu、Yuan Wang、Yanhong Xing、Jing Yu、Hong Ji、Ming Kai、Zilong Wang、Dan Wang、Yixin Zhang、Depeng Zhao、Rui Wang

  DOI：10.1021/jm400195y

  日期：2013.4.11

  Recently we reported the synthesis and structure activity study of endomorphin-1 (EM-1) analogues containing novel, unnatural alpha-methylene-beta-aminopropanoic acids (Map). In the present study, we describe new EM-1 analogues containing Dmt(1), (R/S)-beta Pro(2), and (ph)Map(4)/(2-furyl)Map(4). All of the analogues showed a high affinity for the mu-opioid receptor (MOR) and increased stability in mouse brain homogenates. Of the new compounds, Dmt(1)-(R)-beta Pro(2)-Trp(3)-(2-furyl)Map(4) (analogue 12) displayed the highest affinity toward MOR, in the picomolar range (K-i(mu) = 3.72 pM). Forskolin-induced cAMP accumulation assays indicated that this analogue displayed an extremely high agonistic potency, in the subpicomolar range (EC50 = 0.0421 pM, E-max = 99.5%). This compound also displayed stronger in vivo antinociceptive activity after iv administration when compared to morphine in the tail-flick test, which indicates that this analogue was able to cross the blood-brain barrier.
• Design, synthesis, and evaluation of new endomorphin analogs with enhanced central antinociception after peripheral administration
  作者：Xin Liu、Long Zhao、Yuan Wang、Lingyun Mou、Junxian Yang、Yixin Zhang、Dan Wang、Rui Wang

  DOI：10.1016/j.bmcl.2015.09.025

  日期：2015.11

  We synthesized two novel endomorphin-1 (EM-1) analogs by substituting the C-terminus residue with (thienyl)-alpha-methylene-beta-amino acids (Map). Several in vitro and in vivo assays were used to determine the activity of the analogs. The two EM-1 analogs showed subnanomolar binding affinity and functional activity at the mu-opioid receptor in HEK293 cells. Tail-flick and formalin tests further revealed that the EM-1 analogs were very effective after intravenous administration. Our results indicate that compared to endomorphin-1, the (thienyl)Map modified peptides showed improved blood-brain barrier permeability. (C) 2015 Elsevier Ltd. All rights reserved.