diethyl (3-cyano-2-methylprop-2-enyl)phosphonate | 82648-70-2

• 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: diethyl (3-cyano-2-methylprop-2-enyl)phosphonate
• 英文别名: Diethyl (3-cyano-2-methylallyl)phosphonate；(E)-4-diethoxyphosphoryl-3-methylbut-2-enenitrile
• CAS: 82648-70-2
• 化学式: C₉H₁₆NO₃P
• 分子量: 217.205
• InChiKey: OPUURRZDCJCVGT-RMKNXTFCSA-N

物化性质

• 沸点：
  335.7±35.0 °C(Predicted)
• 密度：
  1.081±0.06 g/cm3(Predicted)
• 溶解度：
  可溶于氯仿（少许）、甲醇（少许）

计算性质

• 辛醇/水分配系数(LogP)：
  0.8
• 重原子数：
  14
• 可旋转键数：
  6
• 环数：
  0.0
• sp3杂化的碳原子比例：
  0.67
• 拓扑面积：
  59.3
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl (3-cyano-2-methylprop-2-enyl)phosphonate 在 二异丁基氢化铝 作用下， 生成 视黄醛
  参考文献：
  名称：

  Wadsworth-Emmons 偶联的 9-Demethyl-9-haloretinals- 纯 (all-E)、(9Z) 和 (11Z) 异构体的简单制备

  摘要：

  5-(2',6',6'-Trimethyl-1'-cyclohexen-1'-yl)-4-penten-2-yn-1-al 以β-紫罗兰酮为原料，一锅法制备几乎定量的产量。使用 1,4- 亲核加成反应，相应的 9-Cl、9-Br、9-I β-亚亚乙基乙醛体系可以作为（9Z）和（全 E）异构体的混合物一步以定量收率获得。甚至相应的氟衍生物也可以作为（9Z）和（全-E）异构体以良好的收率获得。在双键具有卤素取代基的情况下，IUPAC 规则对顺式双键使用 (E) 命名法，对反式双键使用 (Z) 命名法。简单的柱色谱得到纯的 (9Z) 和 (all-E) 形式。优化 Wadsworth-Emmons 偶联得到相应的 (all-E)- 和 (9Z)- 视黄腈定量产率。随后的 DIBAL-H 减少产生相应的视网膜。为了制备对视觉至关重要的 (11Z) 异构体，我们发现 Wadsworth-Emmons

  DOI：

  10.1002/ejoc.200400005
• 作为产物：
  描述：

  4-chloro-3-methylbut-2-enenitrile 、 4-chloro-3-methylbut-2-enenitrile 、 亚磷酸三乙酯 生成 diethyl (3-cyano-2-methylprop-2-enyl)phosphonate
  参考文献：
  名称：

  TREHAN, ACHLA;MIRZADEGAN, TARANEH;LIU, R. S. H., TETRAHEDRON, 46,(1990) N1, C. 3769-3780

  摘要：

  DOI：

文献信息

• Expansion of First-in-Class Drug Candidates That Sequester Toxic All-<i>Trans</i>-Retinal and Prevent Light-Induced Retinal Degeneration
  作者：Jianye Zhang、Zhiqian Dong、Sreenivasa Reddy Mundla、X. Eric Hu、William Seibel、Ruben Papoian、Krzysztof Palczewski、Marcin Golczak

  DOI：10.1124/mol.114.096560

  日期：2015.3

  All- trans -retinal, a retinoid metabolite naturally produced upon photoreceptor light activation, is cytotoxic when present at elevated levels in the retina. To lower its toxicity, two experimentally validated methods have been developed involving inhibition of the retinoid cycle and sequestration of excess of all- trans -retinal by drugs containing a primary amine group. We identified the first-in-class drug candidates that transiently sequester this metabolite or slow down its production by inhibiting regeneration of the visual chromophore, 11- cis -retinal. Two enzymes are critical for retinoid recycling in the eye. Lecithin:retinol acyltransferase (LRAT) is the enzyme that traps vitamin A (all- trans -retinol) from the circulation and photoreceptor cells to produce the esterified substrate for retinoid isomerase (RPE65), which converts all- trans -retinyl ester into 11- cis -retinol. Here we investigated retinylamine and its derivatives to assess their inhibitor/substrate specificities for RPE65 and LRAT, mechanisms of action, potency, retention in the eye, and protection against acute light-induced retinal degeneration in mice. We correlated levels of visual cycle inhibition with retinal protective effects and outlined chemical boundaries for LRAT substrates and RPE65 inhibitors to obtain critical insights into therapeutic properties needed for retinal preservation.

  全反视黄醛是一种视黄酸代谢物，在光感受器光激活后自然产生，当其在视网膜中含量升高时具有细胞毒性。为了降低其毒性，人们已开发出两种实验验证的方法，包括抑制视黄酸循环和通过含有伯胺基团的药物捕获过量的全反视黄醛。我们鉴定了首批候选药物，这些药物通过暂时捕获该代谢物或通过抑制视觉色素11-顺式视黄醛的再生来减缓其产生。在眼睛中，有两种酶对视黄酸的循环至关重要。卵磷脂：视黄醇酰基转移酶（LRAT）是将从循环和光感受器细胞中捕获的维生素A（全反视黄醇）转化为酯化底物的酶，该底物供视黄酸异构酶（RPE65）使用，后者将全反视黄醇酯转化为11-顺式视黄醇。在此，我们研究了视黄胺及其衍生物，以评估它们对RPE65和LRAT的抑制剂/底物特异性、作用机制、效力、在眼睛中的保留能力以及对小鼠急性光诱导视网膜变性的保护作用。我们将视觉循环抑制水平与视网膜保护效应相关联，并概述了LRAT底物和RPE65抑制剂的化学边界，以获得对视网膜保持所需治疗特性的关键洞察。
• Bacteriorhodopsin: The influence of the cyclohexene-ring methyls
  作者：J. M. L. Courtin、L. Verhagen、P. L. Biesheuvel、J. Lugtenburg、R. L. van der Bend、K. van Dam

  DOI：10.1002/recl.19871060402

  日期：——

  of the modified bacteriorhodopsins were much lower than those of the native system. UV-Vis and 1H NMR data support a planar 6-s-trans conformation for the demethylated retinals in solution rather than a twisted 6-s-cis conformation (torsion angle 40-60°) as found in retinal. This explains the lower opsin shift and the better fit of these demethylated retinals in bacteriorhodopsin's binding site, which

  四个环去甲基化视网膜，即。1,1,5'-tridemethylretinal，1,1'-didemethylretinal，1,5-didemethylretinal和1-didemethylretinal已通过新的简单方案合成。研究了这些修饰的视网膜，其质子化的席夫碱和相应的细菌视紫红质的特性，并将其与天然系统进行了比较。还对这些细菌视紫红质类似物的质子泵效率进行了测试。发现缺少5-甲基的类似物的质子泵活性大大降低。总体而言，修饰的细菌视紫红质的视蛋白移位远低于天然系统。UV-Vis和1 H NMR数据支持平面6 -s-trans溶液中去甲基化的视网膜的构象，而不是视网膜中扭曲的6 -s-顺式构象（扭转角40-60°）。这解释了视紫红质视蛋白移位较低，且这些去甲基化的视网膜更适合细菌视紫红质的结合位点，而细菌视紫红质的结合位点以其天然形式包含6 -s-反生色团。
• 5-Demethylretinal and its 5-2H, 7-2H2 and 5,7-2H2 isotopomers. Synthesis, photochemistry and spectroscopy
  作者：M. B. Spijker-Assink、C. Winkel、G. S. Baldwin、J. Lugtenburg

  DOI：10.1002/recl.19881070304

  日期：——

  All-trans-5-demethylretinal and its 5-2H, 7-2H and 5,7-2H2 isotopomers have been synthesized by means of a new and simple scheme. Using photochemistry, the 9-, 11- and 13-cis, as well as the 9,13- and 11,13-di-cis isomers, were obtained. The structures were established by means of 1H NMR spectroscopy.

  清一色反式-5- demethylretinal和其5- 2 H，7- 2 H和5,7- 2 ħ 2同位素已经由新的和简单的方案来合成。使用光化学，获得9-，11-和13-顺式以及9,13-和11,13-顺式异构体。通过1 H NMR光谱确定结构。
• Synthesis of (12,13-13C2)retinal and (13,1413C2)retinal: A strategy to prepare multiple-13C-labeled conjugated systems
  作者：M. Groesbeek、G. A. Rood、J. Lugtenburg

  DOI：10.1002/recl.19921110307

  日期：——

  (12,13-13C2)Retinal, (13,14-13C2)retinal, (19-13C)retinal and (20-13C)retinal (1) were prepared in a simple fashion in high yield via a consecutive strategy. The key step is the reaction of a N-methoxy-N-methylamide with an alkyllithium or a Grignard reagent. The preparation of the required N-methoxy-N-methylamide is discussed. In this scheme, only three commercially available 13C-labeled starting

  （12,13- 13 Ç 2）视黄醛，（13,14- 13 Ç 2）视黄醛，（19- 13 ℃）和视网膜（20- 13 ℃）的视网膜（1）在通过一个简单的方式以高收率制备连续的策略。关键步骤是N-甲氧基-N-甲基酰胺与烷基锂或格氏试剂的反应。讨论了所需的N-甲氧基-N-甲酰胺的制备。在该方案中，只有三种可商购的13 C标记的起始原料（溴乙酸乙酯，乙腈和碘甲烷）足以构成具有13种可能组合的视网膜共轭尾端的C标记。该策略适用于制备许多其他共轭体系，例如类维生素A，类胡萝卜素和多烯。
• 4,5-Didehydro-9-demethyl-9-halo-5,6-dihydroretinals and Their 9-Cyclopropyl and 9-Isopropyl Derivatives− Simple Preparation ofα-Ionone Derivatives and Pure (all-E)-, (9Z)- and (11Z)-α-Retinals
  作者：Yajie Wang、Johan Lugtenburg

  DOI：10.1002/ejoc.200400201

  日期：2004.8

  mixture of (9Z) and (all-E) isomers by 1,4-nucleophilic addition reactions. The pure (all-E) and (9Z) isomers could be separated by simple column chromatography. The corresponding [(9Z)- and (all-E)-9-demethyl-9-fluoro-α-ionylidene]acetaldehydes could also be obtained in pure form by simple column chromatography. These α-ionylidene systems could be easily converted either into the (all-E)-4,5-dideh

  α-紫罗兰酮及其几种化学改性衍生物已通过 Wadsworth-Emmons 程序使用亚氨基膦酸盐阴离子试剂以高产率和完全异构纯度制备。以 α-紫罗兰酮为原料，可制备 5-(2',6',6'-trimethylcyclo-2'-hexen-1'-yl)-4-penten-2-yn-1-al - 锅程序。相应的(9-Cl-、9-Br-和9-I-α-亚亚乙基)乙醛体系可以在(9Z)和(全-E)异构体的定量混合物中通过1,4-亲核反应一步获得。加成反应。纯（全 E）和（9Z）异构体可以通过简单的柱色谱分离。相应的 [(9Z)- 和 (all-E)-9-demethyl-9-fluoro-α-ionylidene] 乙醛也可以通过简单的柱色谱以纯形式获得。这些 α-亚离子系统可以很容易地转化为 (all-E)-4，5-didehydro-9-demethyl-9-halo-5,6-dihydroretinals